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Ye W, Li L, Zeng J. Association of Cardiac Valve Calcification and 1-year Mortality after Lower-extremity Amputation in Diabetic Patients: A Retrospective Study. Curr Neurovasc Res 2024; 20:599-607. [PMID: 38083889 DOI: 10.2174/0115672026277348231130112221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 10/18/2023] [Accepted: 10/24/2024] [Indexed: 07/16/2024]
Abstract
BACKGROUND Cardiac valve calcification predisposes patients to a higher risk of adverse cardiovascular events. This study aimed to investigate the association between cardiac valve calcification and 1-year mortality in diabetic patients after lower-extremity amputation. METHODS This was a retrospective study conducted on the clinical data of diabetic patients who underwent lower-extremity amputation admitted to the Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, China for diabetic foot ulcers needed lower extremity amputation surgery between July 2017 and March 2021. Detailed preoperative medical assessments were performed and recorded. Cardiac valve calcification was assessed using echocardiography at baseline. Oneyear follow-up assessments were conducted and included clinical visits, hospital record assessments, and telephone reviews to obtain the survival status of patients. RESULTS Ninety-three diabetic patients participated in the study. The 1-year follow-up mortality rate after amputation was 24.7%. Compared to the survival group, the prevalence of cardiac valve calcification and the Revised Cardiac Risk Index (RCRI) were higher in the mortality group. In the Cox regression analysis, cardiac valvular calcification (HR=3.427, 95% CI=1.125- 10.443, p =0.030) was found to be an independent predictor of all-cause mortality after amputation. In addition, the patients with both aortic valve calcification and mitral annular calcification had a higher all-cause mortality rate (50%). Receiver operator characteristic curve analysis showed a stronger predictive ability when using a combination of calcified valve number and RCRI (AUC=0.786 95%, CI=0.676-0.896, p =0.000). CONCLUSION In diabetic patients after lower-extremity amputation, cardiac valve calcification was associated with all-cause mortality during 1-year follow-up. Combination of calcified valve number and RCRI score showed a stronger predictive value for mortality.
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Affiliation(s)
- Weibin Ye
- Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510000, China
| | - Li Li
- Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510000, China
| | - Jianfeng Zeng
- Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510000, China
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2
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Dharmarajan S, Speer MY, Pierce K, Lally J, Leaf EM, Lin ME, Scatena M, Giachelli CM. Role of Runx2 in Calcific Aortic Valve Disease in Mouse Models. Front Cardiovasc Med 2021; 8:687210. [PMID: 34778386 PMCID: PMC8585763 DOI: 10.3389/fcvm.2021.687210] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 09/28/2021] [Indexed: 12/31/2022] Open
Abstract
Background: Calcific aortic valve disease is common in the aging population and is characterized by the histological changes of the aortic valves including extracellular matrix remodeling, osteochondrogenic differentiation, and calcification. Combined, these changes lead to aortic sclerosis, aortic stenosis (AS), and eventually to heart failure. Runt-related transcription factor 2 (Runx2) is a transcription factor highly expressed in the calcified aortic valves. However, its definitive role in the progression of calcific aortic valve disease (CAVD) has not been determined. In this study, we utilized constitutive and transient conditional knockout mouse models to assess the molecular, histological, and functional changes in the aortic valve due to Runx2 depletion. Methods: Lineage tracing studies were performed to determine the provenance of the cells giving rise to Runx2+ osteochondrogenic cells in the aortic valves of LDLr-/- mice. Hyperlipidemic mice with a constitutive or temporal depletion of Runx2 in the activated valvular interstitial cells (aVICs) and sinus wall cells were further investigated. Following feeding with a diabetogenic diet, the mice were examined for changes in gene expression, blood flow dynamics, calcification, and histology. Results: The aVICs and sinus wall cells gave rise to Runx2+ osteochondrogenic cells in diseased mouse aortic valves. The conditional depletion of Runx2 in the SM22α+ aVICs and sinus wall cells led to the decreased osteochondrogenic gene expression in diabetic LDLr-/- mice. The transient conditional depletion of Runx2 in the aVICs and sinus wall cells of LDLr-/-ApoB100 CAVD mice early in disease led to a significant reduction in the aortic peak velocity, mean velocity, and mean gradient, suggesting the causal role of Runx2 on the progression of AS. Finally, the leaflet hinge and sinus wall calcification were significantly decreased in the aortic valve following the conditional and temporal Runx2 depletion, but no significant effect on the valve cusp calcification or thickness was observed. Conclusions: In the aortic valve disease, Runx2 was expressed early and was required for the osteochondrogenic differentiation of the aVICs and sinus wall cells. The transient depletion of Runx2 in the aVICs and sinus wall cells in a mouse model of CAVD with a high prevalence of hemodynamic valve dysfunction led to an improved aortic valve function. Our studies also suggest that leaflet hinge and sinus wall calcification, even in the absence of significant leaflet cusp calcification, may be sufficient to cause significant valve dysfunctions in mice.
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Affiliation(s)
| | | | | | | | | | | | | | - Cecilia M. Giachelli
- Department of Bioengineering, University of Washington, Seattle, WA, United States
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3
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Are there any subclinical myocardial dysfunctions in subjects with aortic valve sclerosis? A 3D-speckle tracking echocardiography study. Int J Cardiovasc Imaging 2020; 37:207-213. [PMID: 32888107 DOI: 10.1007/s10554-020-01977-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 08/18/2020] [Indexed: 10/23/2022]
Abstract
Aortic valve sclerosis (AVS) is defined as calcified and thickened aortic leaflets without restriction of leaflet motion. We have not found any studies that previously assessed the effect of AVS on myocardial functions with three dimensional-speckle tracking echocardiography (3D-STE). Therefore, we aimed to identify any early changes in left atrial (LA) myocardial dynamics and/or left ventricular (LV) systolic functions in patients with AVS using 3D-STE. Seventy-five patients with AVS and 80 age- and gender-matched controls were enrolled into the study. The baseline clinical characteristics of the study patients were recorded. Conventional 2D echocardiographic and 3D-STE analyses were performed. The LV-global longitudinal strain (LV-GLS) and LV-global circumferential strain (LV-GCS) were significantly decreased in the AVS (+) group than in the control group (p < 0.001 and p = 0.013, respectively). In multivariate logistic regression analysis; LV-GLS (p < 0.001, odds ratio (OR) = 3.16, 95% confidence interval (CI) 1.42-5.63) and Triglyceride (TG) (p = 0.033, OR = 1.29, 95% CI 1.11-1.72) were found to be independent predictors of AVS. ROC analysis was performed to find out the ideal LV-GLS cut-off value for predicting the AVS. A LV-GLS value of > - 18 has 85.8% sensitivity, 67.5% specificity for the prediction of the AVS. Our results support that subjects with AVS may have subclinical LV deformation abnormalities even though they have not LV pressure overload. According to our findings, patients with AVS should be investigated in terms of atherosclerotic risk factors, their dysmetabolic status should be evaluated and closely followed up for their progression to calcific aortic stenosis.
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4
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Orlando P, Sabbatinelli J, Silvestri S, Marcheggiani F, Cirilli I, Dludla PV, Molardi A, Nicolini F, Tiano L. Ubiquinol supplementation in elderly patients undergoing aortic valve replacement: biochemical and clinical aspects. Aging (Albany NY) 2020; 12:15514-15531. [PMID: 32741773 PMCID: PMC7467386 DOI: 10.18632/aging.103742] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 07/07/2020] [Indexed: 12/24/2022]
Abstract
Epidemiological data show a rise in the mean age of patients affected by heart disease undergoing cardiac surgery. Senescent myocardium reduces the tolerance to ischemic stress and there are indications about age-associated deficit in post-operative cardiac performance. Coenzyme Q10 (CoQ10), and more specifically its reduced form ubiquinol (QH), improve several conditions related to bioenergetic deficit or increased exposure to oxidative stress. This trial (Eudra-CT 2009-015826-13) evaluated the clinical and biochemical effects of ubiquinol in 50 elderly patients affected by severe aortic stenosis undergoing aortic valve replacement and randomized to either placebo or 400 mg/day ubiquinol from 7 days before to 5 days after surgery. Plasma and cardiac tissue CoQ10 levels and oxidative status, circulating troponin I, CK-MB (primary endpoints), IL-6 and S100B were assessed. Moreover, main cardiac adverse effects, NYHA class, contractility and myocardial hypertrophy (secondary endpoints) were evaluated during a 6-month follow-up visit. Ubiquinol treatment counteracted the post-operative plasma CoQ10 decline (p<0.0001) and oxidation (p=0.038) and curbed the post-operative increase in troponin I (QH, 1.90 [1.47-2.48] ng/dL; placebo, 4.03 [2.45-6.63] ng/dL; p=0.007) related to cardiac surgery. Moreover, ubiquinol prevented the adverse outcomes that might have been associated with defective left ventricular ejection fraction recovery in elderly patients.
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Affiliation(s)
- Patrick Orlando
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, Ancona 60100, Italy
| | - Jacopo Sabbatinelli
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona 60100, Italy
| | - Sonia Silvestri
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, Ancona 60100, Italy
| | - Fabio Marcheggiani
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, Ancona 60100, Italy
| | - Ilenia Cirilli
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, Ancona 60100, Italy
| | - Phiwayinkosi Vusi Dludla
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, Ancona 60100, Italy.,Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa
| | - Alberto Molardi
- Cardiac Surgery Department, Parma University Hospital, Parma 43126, Italy
| | - Francesco Nicolini
- Cardiac Surgery Department, Parma University Hospital, Parma 43126, Italy
| | - Luca Tiano
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, Ancona 60100, Italy
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Zhao C, Li G, Li J. Non-coding RNAs and Cardiac Aging. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1229:247-258. [PMID: 32285416 DOI: 10.1007/978-981-15-1671-9_14] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Aging is an important risk factor for cardiovascular diseases. Aging increasing the morbidity and mortality in cardiovascular disease patients. With the society is aging rapidly in the world, medical burden of aging-related cardiovascular diseases increasing drastically. Hence, it is urgent to explore the underlying mechanism and treatment of cardiac aging. Noncoding RNAs (ncRNAs, including microRNAs, long noncoding RNAs and circular RNAs) have been reported to be involved in many pathological processes, including cell proliferation, cell death differentiation, hypertrophy and aging in wide variety of cells and tissues. In this chapter, we will summarize the physiology and molecular mechanisms of cardiac aging. Then, the recent research advances of ncRNAs in cardiac aging will be provided. The lessons learned from ncRNAs and cardiac aging studies would bring new insights into the regulatory mechanisms ncRNAs as well as treatment of aging-related cardiovascular diseases.
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Affiliation(s)
- Cuimei Zhao
- Department of Cardiology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Guoping Li
- Cardiovascular Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Jin Li
- Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, China.
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6
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Cardoso-Saldaña G, Fragoso JM, Lale-Farjat S, Torres-Tamayo M, Posadas-Romero C, Vargas-Alarcón G, Posadas-Sánchez R. The rs10455872-G allele of the LPA gene is associated with high lipoprotein(a) levels and increased aortic valve calcium in a Mexican adult population. Genet Mol Biol 2019; 42:519-525. [PMID: 31188921 PMCID: PMC6905440 DOI: 10.1590/1678-4685-gmb-2017-0371] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 11/28/2018] [Indexed: 11/22/2022] Open
Abstract
Polymorphisms in the LPA gene have been associated with aortic
valve calcification (AVC). There are wide differences in the allelic
frequencies, Lp(a) levels, and the association with AVC among ethnic groups. The
aim of this study was to determine the association of the LPA
gene polymorphisms with Lp(a) levels and risk of developing AVC, in
Mexican-Mestizos population. Six LPA polymorphisms (rs10455872,
rs7765803, rs6907156, rs1321195, rs12212807 and rs6919346) were genotyped by
TaqMan assays in 1,265 individuals without premature coronary artery disease.
The presence of AVC was determined by computed tomography. The association of
the LPA polymorphisms with AVC, Lp(a), and other cardiovascular
risk factors (CVRF) was evaluated using logistic regression analysis. Compared
to AA genotype, subjects with AG+GG genotypes had high prevalence of Lp(a) ≥ 30
mg/dL (7.1% vs. 23.7%, p<0.001) and AVC (19.0% vs. 29.4%,
p=0.007). In a model adjusted for several CVRF, the
LPA rs10455872-G allele was associated with high Lp(a)
levels and AVC. Carriers of G allele had a high risk of Lp(a) ≥ 30 mg/dL (OR=
3.86, CI 95%: 2.2 - 6.7, p=0.001) and AVC (OR= 2.54, CI 95%:
1.56 - 4.14, p=0.001), independently of other CVRF. In this
population, carriers of rs10455872-G allele had 3.86 and 2.54 higher risk of
Lp(a) ≥ 30 mg/dL or presence of AVC, respectively.
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Affiliation(s)
- Guillermo Cardoso-Saldaña
- Department of Endocrinology, Instituto Nacional de Cardiología - Ignacio Chávez, México City, México
| | - José Manuel Fragoso
- Department of Molecular Biology, Instituto Nacional de Cardiología - Ignacio Chávez, México City, México
| | - Shamar Lale-Farjat
- Department of Endocrinology, Instituto Nacional de Cardiología - Ignacio Chávez, México City, México
| | - Margarita Torres-Tamayo
- Department of Endocrinology, Instituto Nacional de Cardiología - Ignacio Chávez, México City, México
| | - Carlos Posadas-Romero
- Department of Endocrinology, Instituto Nacional de Cardiología - Ignacio Chávez, México City, México
| | - Gilberto Vargas-Alarcón
- Department of Molecular Biology, Instituto Nacional de Cardiología - Ignacio Chávez, México City, México
| | - Rosalinda Posadas-Sánchez
- Department of Endocrinology, Instituto Nacional de Cardiología - Ignacio Chávez, México City, México
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7
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Baman JR, Knapper J, Raval Z, Harinstein ME, Friedewald JJ, Maganti K, Cuttica MJ, Abecassis MI, Ali ZA, Gheorghiade M, Flaherty JD. Preoperative Noncoronary Cardiovascular Assessment and Management of Kidney Transplant Candidates. Clin J Am Soc Nephrol 2019; 14:1670-1676. [PMID: 31554619 PMCID: PMC6832054 DOI: 10.2215/cjn.03640319] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The pretransplant risk assessment for patients with ESKD who are undergoing evaluation for kidney transplant is complex and multifaceted. When considering cardiovascular disease in particular, many factors should be considered. Given the increasing incidence of kidney transplantation and the growing body of evidence addressing ESKD-specific cardiovascular risk profiles, there is an important need for a consolidated, evidence-based model that considers the unique cardiovascular challenges that these patients face. Cardiovascular physiology is altered in these patients by abrupt shifts in volume status, altered calcium-phosphate metabolism, high-output states (in the setting of arteriovenous fistulization), and adverse geometric and electrical remodeling, to name a few. Here, we present a contemporary review by addressing cardiomyopathy/heart failure, pulmonary hypertension, valvular dysfunction, and arrhythmia/sudden cardiac death within the ESKD population.
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Affiliation(s)
| | | | - Zankhana Raval
- Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York Presbyterian Hospital, New York, New York; and
| | - Matthew E Harinstein
- Division of Cardiology, Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - John J Friedewald
- Division of Nephrology, Department of Medicine.,Division of Transplantation, Department of Surgery, and
| | | | - Michael J Cuttica
- Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | - Ziad A Ali
- Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York Presbyterian Hospital, New York, New York; and
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8
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Dursun I, Kul S, Bayraktar A, Erkan H, Turan T, Sayin MR, Korkmaz L. Association of Aortic Valve Sclerosis and Clinical Factors in Patients With Acute Myocardial Infarction. Am J Med Sci 2019; 357:474-482. [PMID: 31000422 DOI: 10.1016/j.amjms.2019.03.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Revised: 03/19/2019] [Accepted: 03/20/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND Since aortic valve sclerosis (AVS) and coronary artery disease (CAD) share similar cardiovascular risk factors, we hypothesized that the clinical profile of patients with acute myocardial infarction (AMI) would be worse in the presence of AVS. The aim of this study was to investigate the association between AVS and clinical factors in patients with AMI. METHODS Three hundred and fifteen patients with AMI were consecutively enrolled in the study. Echocardiography was used to assess the aortic valve morphology and left ventricular function. The extent and severity of CAD were assessed by Gensini score and the number of obstructed vessels. The patients were divided into 2 groups according to presence or absence of AVS. RESULTS The overall number of patients with AVS was 132 (41.9%). Patients with AVS were older (69.5 ± 11 vs. 59.5 ± 12 years, P < 0.00001). They also had a higher prevalence of hypertension (61% vs. 45%, P = 0.006), prior CAD (33% vs. 23%, P = 0.041), prior AMI (20% vs. 11%, P = 0.019) and a higher percentage were female (32% vs. 19%, P = 0.007) compared with AMI patients without AVS. There was no significant difference between the 2 groups with respect to the Gensini score (P = 0.372). Prior AMI was associated with AVS on age-adjusted logistic regression analyses. A multivariate analysis showed an independent association between the AVS and prior AMI and age (P < 0.0000001, P = 0.022, respectively). CONCLUSIONS Our results showed that the presence of AVS is associated with AMI recurrence.
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Affiliation(s)
- Ihsan Dursun
- Department of Cardiology, Saglik Bilimleri University, Ahi Evren Thoracic and Cardiovascular Surgery Training and Research Hospital, Trabzon, Turkey.
| | - Selim Kul
- Department of Cardiology, Saglik Bilimleri University, Ahi Evren Thoracic and Cardiovascular Surgery Training and Research Hospital, Trabzon, Turkey
| | - Ali Bayraktar
- Department of Cardiology, Saglik Bilimleri University, Ahi Evren Thoracic and Cardiovascular Surgery Training and Research Hospital, Trabzon, Turkey
| | - Hakan Erkan
- Department of Cardiology, Saglik Bilimleri University, Ahi Evren Thoracic and Cardiovascular Surgery Training and Research Hospital, Trabzon, Turkey
| | - Turhan Turan
- Department of Cardiology, Saglik Bilimleri University, Ahi Evren Thoracic and Cardiovascular Surgery Training and Research Hospital, Trabzon, Turkey
| | - Muhammet Rasit Sayin
- Department of Cardiology, Saglik Bilimleri University, Ahi Evren Thoracic and Cardiovascular Surgery Training and Research Hospital, Trabzon, Turkey
| | - Levent Korkmaz
- Department of Cardiology, Saglik Bilimleri University, Ahi Evren Thoracic and Cardiovascular Surgery Training and Research Hospital, Trabzon, Turkey
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9
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The relationship between endothelial function and aortic valve calcification: Multi-Ethnic Study of Atherosclerosis. Atherosclerosis 2018; 280:155-165. [PMID: 30529828 DOI: 10.1016/j.atherosclerosis.2018.11.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 10/19/2018] [Accepted: 11/16/2018] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND AIMS Aortic valve calcification (AVC) may be associated with atherogenic processes arising from endothelial dysfunction (ED). Limited data is available about the relationship between ED, defined by flow mediated dilation (FMD%) and biomarkers, and the prevalence and progression of AVC in a multiethnic population. METHODS A sample of 3475 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with both initial and repeat CT scans at a mean of 2.65 ± 0.84 years and FMD% and serologic markers of ED [ C-reactive protein (CRP), Von Willebrand factor (vWF), Plasminogen Activator Inhibitor (PAI), fibrinogen, Interleukin 6 (IL6), E-selectin and ICAM-1 (Intercellular Adhesion Molecule 1)], were analyzed. Multivariate modeling evaluated the association between ED and the prevalent AVC and AVC progression. RESULTS The median levels of FMD% was lower and vWF%, fibrinogen, IL6 and ICAM-1 were significantly higher in the AVC prevalence group versus no AVC prevalence (all p < 0.001). In the fully adjusted model for established risk factors, decreasing FMD% or increasing biomarkers was not independently associated with AVC prevalence [OR FMD% 1.028 (0.786, 1.346), CRP 0.981 (0.825, 1.168), vWF 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 1.116 (0.424, 2.940), IL6 1.065 (0.779, 1.456), E-selectin 0.876 (0.479, 1.602) and ICAM-1 1.766 (0.834, 3.743)]. In the AVC progression group, FMD%, vWF%, fibrinogen and IL6 were significantly different (p < 0.05). After adjusting for cardiac risk factors, AVC progression was not independently associated with decreasing FMD% or increasing biomarkers [OR FMD% 1.105 (0.835, 1.463), CRP 1.014 (0.849, 1.210), vWF% 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 0.909 (0.338, 2.443), IL6 1.061 (0.772, 1.459), E-selectin 0.794 (0.426, 1.480) and ICAM-1 0.998 (0.476, 2.092)]. CONCLUSIONS Endothelial dysfunction by FMD% and biomarkers is not significantly associated with the prevalence or progression of aortic valve calcification after adjustment for cardiac risk factors.
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10
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Di Minno MND, Di Minno A, Ambrosino P, Songia P, Pepi M, Tremoli E, Poggio P. Cardiovascular morbidity and mortality in patients with aortic valve sclerosis: A systematic review and meta-analysis. Int J Cardiol 2018; 260:138-144. [PMID: 29622430 DOI: 10.1016/j.ijcard.2018.01.054] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Revised: 12/18/2017] [Accepted: 01/15/2018] [Indexed: 11/17/2022]
Abstract
AIMS The association between aortic valve sclerosis (AVSc) and cardiovascular (CV) events is not consistent among different studies. We have performed a meta-analysis evaluating the association between AVSc and fatal and/or non-fatal CV and cerebrovascular events. METHODS AND RESULTS A systematic search was performed in the electronic databases (PubMed, Web of Science, Scopus, EMBASE). Studies evaluating coronary artery disease (CAD), stroke and CV mortality in AVSc patients and controls were included. Differences among cases and controls were expressed as Odds Ratio (OR) with pertinent 95% Confidence Intervals (CI). Thirty-one studies on 10,537 AVSc patients and 25,005 controls were included in the final analysis. The absolute risk of CAD was 45.8% (95% CI: 32.9-59.3) in AVSc patients and 29.4% (95% CI: 21.8-38.5) in controls with an OR of 2.02 (95% CI: 1.67-2.44) and an attributable risk of 35.8%. Moreover, stroke was reported in 11.8% (95% CI: 4.4-27.7) of AVSc patients and 7.9% (95% CI: 2.5-22.7) of controls (OR: 1.41, 95% CI: 1.16-1.71) with an attributable risk of 33.0%. CV mortality was 6.2% (95% CI: 2.7-13.5) in AVSc patients and 2.0% (95% CI: 0.5-7.9) in controls (OR: 2.70, 95% CI: 1.45-5.01), with an attributable risk of 67.7%. Results were confirmed when pooling together ORs for CAD, stroke and CV mortality obtained by means of multivariate analysis. CONCLUSIONS AVSc is associated with CAD, stroke and CV mortality. Taken together, these data suggest that patients with AVSc may benefit from a stricter CV risk monitoring and that AVSc screening may be included in the frame of CV risk stratification protocols.
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Affiliation(s)
| | - Alessandro Di Minno
- Centro Cardiologico Monzino, IRCCS, Milan, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolare, University of Milan, Milan, Italy
| | - Pasquale Ambrosino
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Paola Songia
- Centro Cardiologico Monzino, IRCCS, Milan, Italy
| | - Mauro Pepi
- Centro Cardiologico Monzino, IRCCS, Milan, Italy
| | | | - Paolo Poggio
- Centro Cardiologico Monzino, IRCCS, Milan, Italy.
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11
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Thoenes M, Bramlage P, Zamorano P, Messika-Zeitoun D, Wendt D, Kasel M, Kurucova J, Steeds RP. Patient screening for early detection of aortic stenosis (AS)-review of current practice and future perspectives. J Thorac Dis 2018; 10:5584-5594. [PMID: 30416809 DOI: 10.21037/jtd.2018.09.02] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
In Europe, approximately one million people over 75 years suffer from severe aortic stenosis (AS), one of the most serious and most common valve diseases, and this disease burden is increasing with the aging population. A diagnosis of severe symptomatic AS is associated with an average life expectancy of 2-3 years and necessitates a timely valve intervention. Guidelines for valve replacement therapy have been established but only a proportion of patients with symptomatic AS actually receive this life-saving treatment. The decision for valve intervention in asymptomatic patients with severe AS is often more challenging and likely results in fewer patients receiving treatment in comparison to their symptomatic counterparts. This article reviews the epidemiology and clinical manifestations of AS, the associated economic burden of AS to the healthcare system, the diagnosis of AS and the possible mechanisms for the introduction of routine screening in elderly patients. Elderly patients typically visit healthcare providers more frequently than younger patients, thereby providing increased opportunities for ad hoc AS screening and this, along with raising patient awareness of the symptoms of AS, has the potential to result in the earlier diagnosis and treatment of AS and increased patient survival.
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Affiliation(s)
- Martin Thoenes
- Léman Research Institute, Schaffhausen am Rheinfall, Switzerland.,Edwards Lifesciences, Nyon, Switzerland
| | - Peter Bramlage
- Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany
| | | | | | - Daniel Wendt
- Klinik für Thorax- und Kardiovaskuläre Chirurgie, Westdeutsches Herzzentrum Essen, Universitätsklinikum Essen, Essen, Germany
| | | | | | - Richard P Steeds
- Queen Elizabeth Hospital & Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK
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Mazzone C, Cioffi G, Di Nora C, Barbati G, Guidetti F, Faggiano P, Gaibazzi N, Faganello G, Borca EC, Di Lenarda A. Prognostic role of cardiac calcifications in primary prevention: A powerful marker of adverse outcome highly dependent on underlying cardiac rhythm. Int J Cardiol 2018; 258:262-268. [DOI: 10.1016/j.ijcard.2018.01.101] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2017] [Revised: 12/06/2017] [Accepted: 01/22/2018] [Indexed: 01/08/2023]
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13
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Aortic calcified particles modulate valvular endothelial and interstitial cells. Cardiovasc Pathol 2017; 28:36-45. [DOI: 10.1016/j.carpath.2017.02.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 02/15/2017] [Accepted: 02/22/2017] [Indexed: 12/11/2022] Open
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Picardo PJ, Khariong PDS, Hajong R, Hajong D, Naku N, Anand M, Sharma G, Singh KL. Study of Aortic Valve Sclerosis as A Marker of Atherosclerosis in Acute Coronary Syndromes. J Clin Diagn Res 2017; 10:OC05-OC09. [PMID: 28208902 DOI: 10.7860/jcdr/2016/22422.8970] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 08/31/2016] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Aortic valve sclerosis has been shown to be associated with increased incidence, chances of developing myocardial infarction and even death. The epidemiological risk factors causing calcification of aortic valves have also been found to cause atherosclerosis. AIM To analyse the epidemiological risk factors causing aortic valve sclerosis which have been studied in details and analysed to see whether they cause any significant increase in the incidence of cardiovascular events. MATERIALS AND METHODS This prospective case-control study was conducted between 1st Jan 2015 to 31st Dec 2015 in NEIGRIHMS hospital and data for age, gender, socioeconomic status, hypertension, diabetes, tobacco use, Body Mass Iindex (BMI), cholesterol levels, Electrocardiography (ECG) changes and Ejection Fraction (EF) were collected and analysed by using SPSS software version 22. RESULTS Hypertension, diabetes, weight, BMI, hyperglycaemia and hyperlipidemia were not found to be significantly associated with aortic valve sclerosis in patients presenting with acute coronary syndromes. The presence of aortic valve sclerosis was also not associated with increased risk of cardiovascular mortality and morbidity. CONCLUSION The risk factors for atherosclerosis were found to be associated with the presence of aortic valve sclerosis more in the control group and hence finding of a sclerosed aortic valve in the apparent normal population might identify those persons at increased risk of developing coronary artery disease and appropriate preventive measures should be taken before the disease sets in.
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Affiliation(s)
- Preeti Jane Picardo
- Resident Doctor, Department of Medicine, NEIGRIHMS , Shillong, Meghalaya, India
| | | | - Ranendra Hajong
- Associate Professor, Department of Surgery, NEIGRIHMS , Shillong, Meghalaya, India
| | - Debobratta Hajong
- Resident Doctor, Department of Surgery, NEIGRIHMS , Shillong, Meghalaya, India
| | - Narang Naku
- Resident Doctor, Department of Surgery, NEIGRIHMS , Shillong, Meghalaya, India
| | - Madhur Anand
- Resident Doctor, Department of Surgery, NEIGRIHMS , Shillong, Meghalaya, India
| | - Girish Sharma
- Resident Doctor, Department of Surgery, NEIGRIHMS , Shillong, Meghalaya, India
| | - K Lenish Singh
- Resident Doctor, Department of Surgery, NEIGRIHMS , Shillong, Meghalaya, India
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15
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Revilla‐Orodea A, Toro-Gil JA, Sevilla T, Sánchez‐Lite I, Goncalves-Ramírez LR, Amat-Santos IJ, Cortés-Villar C, Gómez-Salvador I, San Román JA. Coronary artery and aortic valve calcification evaluated with cardiac computed tomography in patients with chest pain: Prognostic value in clinical practice. Int J Cardiol 2016; 219:247-50. [DOI: 10.1016/j.ijcard.2016.06.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 06/12/2016] [Indexed: 10/21/2022]
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16
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[Aortic valve calcification prevalence and association with coronary risk factors and atherosclerosis in Mexican population]. ARCHIVOS DE CARDIOLOGIA DE MEXICO 2016; 87:108-115. [PMID: 27389533 DOI: 10.1016/j.acmx.2016.05.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Revised: 05/25/2016] [Accepted: 05/30/2016] [Indexed: 11/21/2022] Open
Abstract
OBJETIVE The prevalence of aortic valve calcification (AVC), strongly influenced by ethnicity, is unknown in Mexican population. The aim of this study was to investigate the prevalence of AVC and its associations with cardiovascular risk factors and coronary artery calcification (CAC), in Mexican subjects. METHODS In 1,267 subjects (53% women) without known coronary heart disease, aged 35 to 75 years, AVC and CAC were assessed by multidetector-computed tomography using the Agatston score. Cardiovascular risk factors were documented in all participants. The associations of AVC with CAC and risk factors were assessed by multivariable logistic regression analyses. RESULTS The overall prevalence of AVC and CAC was 19.89% and 26.5%, respectively. AVC and CAC increased with age and were found more frequently in men (25.5% and 37.1%, respectively) than in women (14.9% and 13.0%, respectively). AVC was observed in only 8.5% of subjects without CAC, while those with CAC 1-99, 100-399, and >400 Agatston units had AVC prevalences of 36.8%, 56.8%, and 84.0%, respectively. The multivariable logistic regression analyses, adjusted for age, gender, obesity, physical inactivity, hypertension, dyslipidemia and high insulin levels, showed that the presence of CAC (OR [CI95%]: 3.23 [2.26-4.60]), obesity (1.94 [1.35-2.79]), male gender (1.44 [1.01-2.05]) and age (1.08 [1.03-1.10]), were significant independent predictors of AVC. CONCLUSION Prevalence of AVC is high and significantly associated with atherosclerotic risk factors and CAC in this Mexican population.
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Acartürk E, Bozkurt A, Cayli M, Demir M. Mitral Annular Calcification and Aortic Valve Calcification May Help in Predicting Significant Coronary Artery Disease. Angiology 2016; 54:561-7. [PMID: 14565631 DOI: 10.1177/000331970305400505] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Mitral annular calcification (MAC) and aortic valve calcification (AVC) are manifestations of atherosclerosis. To determine whether mitral annular calcification and aortic valve calcification detected by transthoracic echocardiography (TTE) might help in predicting significant coronary artery disease (CAD), 123 patients with significant CAD and 93 patients without CAD detected by coronary angiography were investigated. MAC and AVC identified CAD with a sensitivity and specificity of 60.2%, 55.9% and 74.8%, 52.7%, respectively, and with a negative and a positive predictive values of 51.5%, 64.3% and 61.3% and 67.6%, respectively. The positive predictive value of MAC was greater than gender, hypertension, and hypercholesterolemia. AVC showed a positive predictive value greater than gender, hypertension, family history, and hypercho lesterolemia. The negative predictive values of MAC and AVC for CAD were greater than those of all risk factors except diabetes mellitus. In conclusion, presence of MAC and AVC on TTE may help in predicting CAD and should be added to conventional risk factors. Absence of MVC and AVC is a stronger predictor for absence of CAD than all conventional risk factors, except diabetes mellitus. Patients with MAC and AVC should be taken into consideration for the presence of significant CAD and thereby for diagnostic and therapeutic interventions in order to improve the prognosis.
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Affiliation(s)
- Esmeray Acartürk
- Department of Cardiology, Cukurova University, School of Medicine, 01330 Adana, Turkey.
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18
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Prognostic value of heart valve calcifications for cardiovascular events in a lung cancer screening population. Int J Cardiovasc Imaging 2015; 31:1243-9. [PMID: 25962863 PMCID: PMC4486764 DOI: 10.1007/s10554-015-0664-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Accepted: 04/15/2015] [Indexed: 10/28/2022]
Abstract
To assess the prognostic value of aortic valve and mitral valve/annulus calcifications for cardiovascular events in heavily smoking men without a history of cardiovascular disease. Heavily smoking men without a cardiovascular disease history who underwent non-contrast-enhanced low-radiation-dose chest CT for lung cancer screening were included. Non-imaging predictors (age, smoking status and pack-years) were collected and imaging-predictors (calcium volume of the coronary arteries, aorta, aortic valve and mitral valve/annulus) were obtained. The outcome was the occurrence of cardiovascular events. Multivariable Cox proportional-hazards regression was used to calculate hazard-ratios (HRs) with 95% confidence interval (CI). Subsequently, concordance-statistics were calculated. In total 3111 individuals were included, of whom 186 (6.0%) developed a cardiovascular event during a follow-up of 2.9 (Q1-Q3, 2.7-3.3) years. If aortic (n = 657) or mitral (n = 85) annulus/valve calcifications were present, cardiovascular event incidence increased to 9.0% (n = 59) or 12.9% (n = 11), respectively. HRs of aortic and mitral valve/annulus calcium volume for cardiovascular events were 1.46 (95% CI, 1.09-1.84) and 2.74 (95% CI, 0.92-4.56) per 500 mm(3). The c-statistic of a basic model including age, pack-years, current smoking status, coronary and aorta calcium volume was 0.68 (95% CI, 0.63-0.72), which did not change after adding heart valve calcium volume. Aortic valve calcifications are predictors of future cardiovascular events. However, there was no added prognostic value beyond age, number of pack-years, current smoking status, coronary and aorta calcium volume for short term cardiovascular events.
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19
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Milin AC, Vorobiof G, Aksoy O, Ardehali R. Insights into aortic sclerosis and its relationship with coronary artery disease. J Am Heart Assoc 2014; 3:e001111. [PMID: 25193296 PMCID: PMC4323780 DOI: 10.1161/jaha.114.001111] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Alexandra C Milin
- Department of Internal Medicine, Division of Cardiology, David Geffen School of Medicine at UCLA
| | - Gabriel Vorobiof
- Department of Internal Medicine, Division of Cardiology, David Geffen School of Medicine at UCLA
| | - Olcay Aksoy
- Department of Internal Medicine, Division of Cardiology, David Geffen School of Medicine at UCLA
| | - Reza Ardehali
- Department of Internal Medicine, Division of Cardiology, David Geffen School of Medicine at UCLA
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20
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Wurster T, Tegtmeyer R, Borst O, Rath D, Geisler T, Gawaz M, Bigalke B. Platelet expression of stromal cell-derived factor-1 is associated with the degree of valvular aortic stenosis. PLoS One 2014; 9:e97405. [PMID: 24834915 PMCID: PMC4023969 DOI: 10.1371/journal.pone.0097405] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Accepted: 04/19/2014] [Indexed: 11/18/2022] Open
Abstract
Background and Purpose Platelet surface expression of stromal-cell-derived factor-1 (SDF-1) is increased during platelet activation and constitutes an important factor in hematopoetic progenitor cell trafficking at sites of vascular injury and ischemia. Enhanced platelet SDF-1 expression has been reported previously in patients suffering from acute coronary syndrome (ACS). We hypothesized that expression of platelet associated SDF-1 may also be influenced by calcified valvular aortic stenosis (AS). Methods We consecutively evaluated 941 patients, who were admitted to the emergency department with dyspnea and chest pain. Platelet surface expression of SDF-1 was determined by flow cytometry, AS was assessed using echocardiography and hemodynamic assessment by heart catheterization. A 1∶1 propensity score matching was implemented to match 218 cases with 109 pairs adjusting for age, sex, cardiovascular risk factors, and medication including ACE inhibitors, angiotensin receptor blockers, beta blockers, statins, aspirin, clopidogrel, GPIIb/IIIa antagonists, and vitamin K antagonists. Results Patients with valvular AS showed enhanced platelet SDF-1 expression compared to patients without AS (non-valvular disease, NV) independent of ACS and stable coronary artery disease (SAP) [mean fluorescence intensity (MFI) for ACS (AS vs. NV): 75±40.4 vs. 39.5±23.3; P = 0.002; for SAP (AS vs. NV): 54.9±44.6 vs. 24.3±11.2; P = 0.008]. Moreover, the degree of AS significantly correlated with SDF-1 platelet surface expression (r = 0.462; P = 0.002). Conclusions Valvular AS is associated with enhanced platelet-SDF-1 expression; moreover the degree of valvular AS correlates with SDF-1 platelet surface expression. These findings may have clinical implications in the future.
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Affiliation(s)
- Thomas Wurster
- Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Germany
| | - Roland Tegtmeyer
- Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Germany
| | - Oliver Borst
- Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Germany
| | - Dominik Rath
- Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Germany
| | - Tobias Geisler
- Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Germany
| | - Meinrad Gawaz
- Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Germany
| | - Boris Bigalke
- Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Germany; King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom
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Coffey S, d'Arcy JL, Loudon MA, Mant D, Farmer AJ, Prendergast BD. The OxVALVE population cohort study (OxVALVE-PCS)-population screening for undiagnosed valvular heart disease in the elderly: study design and objectives. Open Heart 2014; 1:e000043. [PMID: 25332795 PMCID: PMC4195926 DOI: 10.1136/openhrt-2014-000043] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 03/12/2014] [Accepted: 04/24/2014] [Indexed: 02/06/2023] Open
Abstract
Introduction Valvular heart disease (VHD) is an increasingly important cardiac condition, driven by an ageing population and lack of progress in the development of medical therapies. There is a dearth of accurate information to guide decision-makers in the development of strategies to combat VHD, and no population-based study has been performed specifically to investigate its contemporary epidemiology. This document describes the design and methodology of the OxVALVE population cohort study (OxVALVE-PCS), which was conceived to address this need. Methods and analysis Participants aged 65 years and older attending a participating general practice in Oxfordshire, UK, are invited to attend a screening examination. Exclusion criteria include previously diagnosed VHD, inability to provide consent, terminal illness or excessive frailty. Demographics, a focused cardiovascular history and vital signs are recorded at the initial screening examination, accompanied by an echocardiogram. Any finding of significant VHD triggers a separate, more formal echocardiographic assessment (including acquisition of a three-dimensional dataset) and collection of blood samples for future genetic and biomarker analysis. Participants provide consent for longitudinal follow-up and enrolment in future cohort substudies. We also assess the acceptability of community-based echocardiographic examination and compare self-assessed quality of life between those with and without VHD. Conclusions OxVALVE-PCS will provide contemporary epidemiological data concerning the community prevalence of undiagnosed VHD, facilitate accurate deployment of scarce resources to meet the anticipated increase in demand for VHD-associated healthcare and create a series of subcohorts with carefully defined genotypes and echocardiographic phenotypes for long overdue clinical studies. Ethics and dissemination This study was approved by the local research ethics committee (Southampton, UK; REC Ref: 09/H0502/58). Results Results will be submitted for publication in peer-reviewed scientific journals.
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Affiliation(s)
- Sean Coffey
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford University Hospitals NHS Trust , Oxford , UK
| | - Joanna L d'Arcy
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford University Hospitals NHS Trust , Oxford , UK
| | - Margaret A Loudon
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford University Hospitals NHS Trust , Oxford , UK
| | - David Mant
- Department of Primary Care Health Sciences , NIHR School for Primary Care Research, University of Oxford , Oxford , UK
| | - Andrew J Farmer
- Department of Primary Care Health Sciences , NIHR School for Primary Care Research, University of Oxford , Oxford , UK
| | - Bernard D Prendergast
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford University Hospitals NHS Trust , Oxford , UK
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Coffey S, Cox B, Williams MJA. The prevalence, incidence, progression, and risks of aortic valve sclerosis: a systematic review and meta-analysis. J Am Coll Cardiol 2014; 63:2852-61. [PMID: 24814496 DOI: 10.1016/j.jacc.2014.04.018] [Citation(s) in RCA: 177] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2013] [Revised: 03/06/2014] [Accepted: 04/18/2014] [Indexed: 11/29/2022]
Abstract
OBJECTIVES The aim of this study was to comprehensively review the epidemiology of aortic sclerosis (ASc) and its association with cardiovascular events. BACKGROUND ASc, which is defined as thickening or calcification of the aortic valve without significant obstruction of blood flow, is a common finding on cardiac imaging. METHODS We searched MEDLINE and EMBASE from inception to April 2013 for studies describing the epidemiology of ASc and performed a meta-analysis of the risk of adverse events using a random effects model. RESULTS Twenty-two studies were identified from the systematic review. The prevalence of ASc increased in proportion to the average age of study participants, ranging from 9% in a study in which the mean age was 54 years to 42% in a study in which the mean age was 81 years. In total, 1.8% to 1.9% of participants with ASc had progression to clinical aortic stenosis per year. There was a 68% increased risk of coronary events in subjects with ASc (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.31 to 2.15), a 27% increased risk of stroke (HR: 1.27; 95% CI: 1.01 to 1.60), a 69% increased risk of cardiovascular mortality (HR: 1.69; 95% CI: 1.32 to 2.15), and a 36% increased risk of all-cause mortality (HR: 1.36; 95% CI: 1.17 to 1.59). CONCLUSIONS ASc is a common finding that is more prevalent with older age. Despite low rates of progression to ASc, there is an independent increase in morbidity and mortality associated with the condition.
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Affiliation(s)
- Sean Coffey
- Department of Cardiology, Oxford University Hospitals, Oxford, United Kingdom; Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
| | - Brian Cox
- Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
| | - Michael J A Williams
- Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
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Lazaros G, Toutouzas K, Drakopoulou M, Boudoulas H, Stefanadis C, Rajamannan N. Aortic sclerosis and mitral annulus calcification: a window to vascular atherosclerosis? Expert Rev Cardiovasc Ther 2014; 11:863-77. [DOI: 10.1586/14779072.2013.811978] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Rossi A, Faggiano P, Amado AE, Cicoira M, Bonapace S, Franceschini L, Dini FL, Ghio S, Agricola E, Temporelli PL, Vassanelli C. Mitral and aortic valve sclerosis/calcification and carotid atherosclerosis: results from 1065 patients. Heart Vessels 2013; 29:776-83. [PMID: 24196525 DOI: 10.1007/s00380-013-0433-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Accepted: 10/18/2013] [Indexed: 01/20/2023]
Abstract
This study assesses whether aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are associated with carotid artery atherosclerosis, independently of traditional cardiovascular risk factors. A total of 1065 patients underwent both echocardiography and carotid artery ultrasound scanning. AVS and MAC were defined as focal areas of increased echogenicity and thickening of the aortic leaflets or mitral valve annulus. Carotid artery atherosclerosis was defined as presence/absence of any atherosclerotic plaque or presence/absence of plaque >50 %. Of 1065 patients (65 ± 9 years; 38 % female) who comprised the study population, 642 (60 %) had at least one atherosclerotic plaque. AVS, but not mitral valve sclerosis; was associated with the presence of carotid atherosclerosis (odds ratio (OR) 1.9, 95 % confidence interval (CI) 1.2-3.9; P = 0.005) and the degree of carotid atherosclerosis (OR 2.1, 95 % CI 1.2-3.9; P = 0.01) in a multivariate model including age, gender, previous ischemic heart disease, hypertension, dyslipidemia, smoking, diabetes, family cardiovascular history, left ventricular size, mass, and ejection fraction, and left atrial size. AVS is a significant predictor of carotid atherosclerosis, independently of other cardiovascular clinical and echocardiographic risk factors.
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Affiliation(s)
- Andrea Rossi
- Dipartimento di Medicina, Sezione di Cardiologia, University of Verona, Verona, Italy,
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Aronow WS. A review of the pathophysiology, diagnosis, and treatment of aortic valve stenosis in elderly patients. Hosp Pract (1995) 2013; 41:66-77. [PMID: 24145591 DOI: 10.3810/hp.2013.10.1082] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Elderly patients experiencing valvular aortic stenosis (AS) show an increased prevalence of coronary risk factors, coronary artery disease, and other atherosclerotic vascular diseases. Angina pectoris, syncope or near syncope, and congestive heart failure are the 3 classic manifestations of severe AS in patients. Prolonged duration and late peaking of an aortic systolic ejection murmur best differentiate severe AS from mild AS upon physical examination of the patient. Doppler echocardiography is used to diagnose the severity of patient AS. In the article, indications for aortic valve replacement (AVR) in patients, the use of warfarin after AVR in patients with mechanical prostheses, and the use of aspirin or warfarin after AVR in patients with bioprosthesis are discussed. Transcatheter aortic valvular replacement should be performed in non-operable patients with symptomatic severe AS to improve their survival and quality of life rather than using regular medical management of the condition.
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Affiliation(s)
- Wilbert S Aronow
- Cardiology Division, Department of Medicine, Westchester Medical Center/New York Medical College, Valhalla, New York.
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Wasilewski J, Mirota K, Wilczek K, Głowacki J, Poloński L. Calcific aortic valve damage as a risk factor for cardiovascular events. Pol J Radiol 2012; 77:30-4. [PMID: 23269934 PMCID: PMC3529709 DOI: 10.12659/pjr.883626] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2012] [Accepted: 10/22/2012] [Indexed: 11/25/2022] Open
Abstract
Aortic valve calcification (AVC) is a common disease of the elderly. It is a progressive disease ranging from mild valve thickening to severe calcification with aortic valve stenosis. Risk factors for AVC are similar to those for atherosclerosis: age, gender, hypercholesterolemia, diabetes, hypertension, smoking and renal failure. AVC shares many similarities to atherosclerosis, including inflammatory cells and calcium deposits, and correlates with coronary plaque burden. Presence of AVC is associated with increased risk of adverse cardiovascular events. The objective for this review is to discuss the clinical features, natural history and prognostic significance of aortic valve calcifications, including mechanical and hemodynamic factors of flow distribution.
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Affiliation(s)
- Jarosław Wasilewski
- 3 Department of Cardiology, Silesian Center for Heart Diseases, Medical University of Silesia, Zabrze, Poland
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Yamazato R, Yamamoto H, Tadehara F, Teragawa H, Kurisu S, Dohi Y, Ishibashi K, Kunita E, Utsunomiya H, Oka T, Kihara Y. Association between aortic valve calcification and myocardial ischemia, especially in asymptomatic patients. J Nucl Med 2012; 53:1216-1221. [PMID: 22855836 DOI: 10.2967/jnumed.111.099275] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
UNLABELLED Aortic valve calcification (AVC) is recognized as a manifestation of systemic arteriosclerosis. However, it is unclear whether AVC is associated with myocardial ischemia. Stress myocardial perfusion SPECT (MPS) is widely used for the diagnosis of myocardial ischemia. However, routine MPS is not recommended, particularly in asymptomatic patients. Accordingly, we investigated the hypothesis that the presence of AVC is strongly associated with inducible myocardial ischemia, even among asymptomatic patients. METHODS We investigated 669 consecutive patients who underwent both adenosine stress (201)Tl MPS and echocardiography. We evaluated the extent and severity of myocardial ischemia by the summed difference score (SDS). We defined the presence of myocardial ischemia as SDS ≥ 3 and moderate to severe ischemia as SDS ≥ 8. We classified the severity of AVC according to the number of affected aortic leaflets. We also compared the mean SDS and the prevalence of SDS ≥ 3 and SDS ≥ 8 among patients stratified by the severity of AVC. RESULTS The presence of AVC was significantly associated with myocardial ischemia (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.10-2.23; P = 0.013) and moderate to severe ischemia (OR, 2.16; 95% CI, 1.26-3.80; P = 0.0061). In 311 asymptomatic patients, AVC was strongly associated with moderate to severe ischemia (OR, 4.31; 95% CI, 1.67-12.8; P = 0.0043). However, the SDS value and the prevalence of SDS ≥ 3 and SDS ≥ 8 did not increase with increasing number of affected aortic leaflets. CONCLUSION The presence of AVC may be associated with the presence of myocardial ischemia, particularly in asymptomatic patients. However, we found no association between the extent of AVC and inducible myocardial ischemia. The presence of AVC may be a useful anatomic marker to help identify patients at high risk of myocardial ischemia, particularly asymptomatic patients.
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Affiliation(s)
- Ryo Yamazato
- Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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Sverdlov AL, Ngo DT, Chan WP, Chirkov YY, Gersh BJ, McNeil JJ, Horowitz JD. Determinants of aortic sclerosis progression: implications regarding impairment of nitric oxide signalling and potential therapeutics. Eur Heart J 2012; 33:2419-25. [DOI: 10.1093/eurheartj/ehs171] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
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Dai DF, Chen T, Johnson SC, Szeto H, Rabinovitch PS. Cardiac aging: from molecular mechanisms to significance in human health and disease. Antioxid Redox Signal 2012; 16:1492-526. [PMID: 22229339 PMCID: PMC3329953 DOI: 10.1089/ars.2011.4179] [Citation(s) in RCA: 235] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cardiovascular diseases (CVDs) are the major causes of death in the western world. The incidence of cardiovascular disease as well as the rate of cardiovascular mortality and morbidity increase exponentially in the elderly population, suggesting that age per se is a major risk factor of CVDs. The physiologic changes of human cardiac aging mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased prevalence of atrial fibrillation, and decreased maximal exercise capacity. Many of these changes are closely recapitulated in animal models commonly used in an aging study, including rodents, flies, and monkeys. The application of genetically modified aged mice has provided direct evidence of several critical molecular mechanisms involved in cardiac aging, such as mitochondrial oxidative stress, insulin/insulin-like growth factor/PI3K pathway, adrenergic and renin angiotensin II signaling, and nutrient signaling pathways. This article also reviews the central role of mitochondrial oxidative stress in CVDs and the plausible mechanisms underlying the progression toward heart failure in the susceptible aging hearts. Finally, the understanding of the molecular mechanisms of cardiac aging may support the potential clinical application of several "anti-aging" strategies that treat CVDs and improve healthy cardiac aging.
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Affiliation(s)
- Dao-Fu Dai
- Department of Pathology, University of Washington, Seattle, Washington, USA
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Bodegard J, Skretteberg PT, Gjesdal K, Pyörälä K, Kjeldsen SE, Liestøl K, Erikssen G, Erikssen J. Low-grade systolic murmurs in healthy middle-aged individuals: innocent or clinically significant? A 35-year follow-up study of 2014 Norwegian men. J Intern Med 2012; 271:581-8. [PMID: 22061296 DOI: 10.1111/j.1365-2796.2011.02480.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To determine whether a low-grade systolic murmur, found at heart auscultation, in middle-aged healthy men influences the long-term risk of aortic valve replacement (AVR) and death from cardiovascular disease (CVD). Setting and subjects. During 1972-1975, 2014 apparently healthy men aged 40-59 years underwent an examination programme including case history, clinical examination, blood tests and a symptom-limited exercise ECG test. Heart auscultation was performed under standardized conditions, and murmurs were graded on a scale from I to VI. No men were found to have grade V/VI murmurs. Participants were followed for up to 35 years. RESULTS A total of 1541 men had no systolic murmur; 441 had low-grade murmurs (grade I/II) and 32 had moderate-grade murmurs (grade III/IV). Men with low-grade murmurs had a 4.7-fold [95% confidence interval (CI) 2.1-11.1] increased age-adjusted risk of AVR, but no increase in risk of CVD death. Men with moderate-grade murmurs had an 89.3-fold (95% CI 39.2-211.2) age-adjusted risk of AVR and a 1.5-fold (95% CI 0.8-2.5) age-adjusted increased risk of CVD death. CONCLUSIONS Low-grade systolic murmur was detected at heart auscultation in 21.9% of apparently healthy middle-aged men. Men with low-grade murmur had an increased risk of AVR, but no increase in risk of CVD death. Only 1.6% of men had moderate-grade murmur; these men had a very high risk of AVR and a 1.5-fold albeit non-significant increase in risk of CVD death.
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Affiliation(s)
- J Bodegard
- Department of Cardiology, Oslo University Hospital, Ullevaal Faculty of Medicine, University of Oslo, Oslo, Norway.
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Rossi A, Faggiano P, Amado AE, Cicoira M, Bonapace S, Franceschini L, Dini Lloyd F, Ghio S, Agricola E, Temporelli PL, Vassanelli C. Aortic valve sclerosis is a marker of atherosclerosis independently of traditional clinical risk factors. Analysis in 712 patients without ischemic heart disease. Int J Cardiol 2012; 158:163-4. [DOI: 10.1016/j.ijcard.2012.04.101] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2011] [Revised: 03/12/2012] [Accepted: 04/14/2012] [Indexed: 01/08/2023]
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Masuda C, Dohi K, Sakurai Y, Bessho Y, Fukuda H, Fujii S, Sugimoto T, Tanabe M, Onishi K, Shiraki K, Ito M, Nobori T. Impact of chronic kidney disease on the presence and severity of aortic stenosis in patients at high risk for coronary artery disease. Cardiovasc Ultrasound 2011; 9:31. [PMID: 22087774 PMCID: PMC3228740 DOI: 10.1186/1476-7120-9-31] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2011] [Accepted: 11/16/2011] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE We evaluated the impact of chronic kidney disease (CKD) on the presence and severity of aortic stenosis (AS) in patients at high risk for coronary artery disease (CAD). METHODS One hundred and twenty consecutive patients who underwent invasive coronary angiography were enrolled. Aortic valve area (AVA) was calculated by the continuity equation using transthoracic echocardiography, and was normalized by body surface area (AVA index). RESULTS Among all 120 patients, 78% had CAD, 55% had CKD (stage 3: 81%; stage 4: 19%), and 34% had AS (AVA < 2.0 cm²). Patients with AS were older, more often female, and had a higher frequency of CKD than those without AS, but the prevalence of CAD and most other coexisting conventional risk factors was similar between patients with and without AS. Multivariate linear regression analysis indicated that only CKD and CAD were independent determinants of AVA index with standardized coefficients of -0.37 and -0.28, respectively. When patients were divided into 3 groups (group 1: absence of CKD and CAD, n = 16; group 2: presence of either CKD or CAD, n = 51; and group 3: presence of both CKD and CAD, n = 53), group 3 had the smallest AVA index (1.19 ± 0.30*# cm²/m², *p < 0.05 vs. group 1: 1.65 ± 0.32 cm²/m², and #p < 0.05 vs. group 2: 1.43 ± 0.29* cm²/m²) and the highest peak velocity across the aortic valve (1.53 ± 0.41*# m/sec; *p < 0.05 vs. group 1: 1.28 ± 0.29 m/sec, and #p < 0.05 vs. group 2: 1.35 ± 0.27 m/sec). CONCLUSION CKD, even pre-stage 5 CKD, has a more powerful impact on the presence and severity of AS than other conventional risk factors for atherosclerosis in patients at high risk for CAD.
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Affiliation(s)
- Chiaki Masuda
- Central Laboratory, Mie University Graduate School of Medicine
| | - Kaoru Dohi
- Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine
| | - Yuko Sakurai
- Central Laboratory, Mie University Graduate School of Medicine
| | - Yuri Bessho
- Central Laboratory, Mie University Graduate School of Medicine
| | - Harumi Fukuda
- Central Laboratory, Mie University Graduate School of Medicine
| | - Shinobu Fujii
- Central Laboratory, Mie University Graduate School of Medicine
| | - Tadafumi Sugimoto
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
| | - Masaki Tanabe
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
| | - Katsuya Onishi
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
| | - Katsuya Shiraki
- Department of Gastroenterology, Mie University Graduate School of Medicine
| | - Masaaki Ito
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine
| | - Tsutomu Nobori
- Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine
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Nightingale AK, Sverdlov AL, Rajendran S, Mishra K, Heresztyn T, Ngo DTM, Horowitz JD. Lack of association between aortic sclerosis and left ventricular hypertrophy in elderly subjects. Int J Cardiol 2011; 150:33-38. [PMID: 20236713 DOI: 10.1016/j.ijcard.2010.02.024] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2009] [Revised: 11/28/2009] [Accepted: 02/14/2010] [Indexed: 11/21/2022]
Abstract
BACKGROUND The presence of aortic sclerosis has been associated with increased LV mass, particularly in hypertensive subjects. However, aortic sclerosis has also been associated with endothelial dysfunction, which may provide stimuli for development of left ventricular hypertrophy independent of afterload. Thus, we have sought to determine whether aortic sclerosis is a determinant of increased left ventricular mass in a non-hypertensive cohort of aging subjects. METHODS 79 subjects, mean age 68 ± 6 years, without existing cardiovascular disease or previous antihypertensive therapy were studied. LV volumes were calculated from the short axis stack of cardiac MRI and LV mass was indexed to height(2.7). The presence of aortic sclerosis was assessed with echocardiography using backscatter from the aortic valve (AV(BS)) and visual scoring. Plasma asymmetric dimethylarginine levels and vascular responses to salbutamol were used to assess endothelial function. ANCOVA was used to test the relationship between LV mass index and afterload. Univariate and multivariate analyses were performed to find determinants of increased LV mass. RESULTS 15 (19%) of subjects had aortic sclerosis on the basis of AV(BS); none had aortic valve areas <1.5 cm(2). There was no significant difference in LV mass between subjects with and without aortic sclerosis. While LV mass was directly related to systolic blood pressure, this relationship was independent of the presence/absence of aortic sclerosis. On multivariate analysis, significant correlates of increased LV mass were male gender, systolic blood pressure and increased BMI, but not presence of aortic sclerosis. CONCLUSIONS In this aging normotensive population free of established cardiovascular disease, aortic sclerosis is not associated with left ventricular hypertrophy.
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Affiliation(s)
- Angus K Nightingale
- Department of Cardiology, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia; Bristol Heart Institute, Bristol, UK
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Toro R, Mangas A, Gómez F. Enfermedad de la válvula aórtica calcificada. Su asociación con la arteriosclerosis. Med Clin (Barc) 2011; 136:588-93. [DOI: 10.1016/j.medcli.2010.02.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2009] [Revised: 02/03/2010] [Accepted: 02/04/2010] [Indexed: 10/19/2022]
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Gharacholou SM, Karon BL, Shub C, Pellikka PA. Aortic valve sclerosis and clinical outcomes: moving toward a definition. Am J Med 2011; 124:103-10. [PMID: 21295189 DOI: 10.1016/j.amjmed.2010.10.012] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2010] [Revised: 10/20/2010] [Accepted: 10/25/2010] [Indexed: 10/18/2022]
Abstract
The presence of aortic valve sclerosis has been suggested as a marker of increased cardiovascular risk, including increased mortality. However, it remains unclear whether aortic valve sclerosis is independently associated with risk or merely a marker of coexistent cardiovascular risk factors. Aortic valve sclerosis is usually diagnosed on transthoracic echocardiography, the most widely used imaging modality in observational and natural history studies of aortic valve disease. Defining aortic valve sclerosis has remained challenging due to the variable and qualitative nature of its description by ultrasound techniques. Importantly, artifacts common to ultrasound imaging and awareness of demographic and clinical history information may bias the diagnosis of aortic valve sclerosis. Because clinicians may alter treatment recommendations or follow-up based on echocardiographic reporting of aortic valve sclerosis, highlighting pitfalls of the subjective nature by which aortic valve sclerosis is identified and establishing diagnostic criteria are necessary. This review describes the diagnostic criteria for aortic valve sclerosis used in outcome studies, summarizes the epidemiological findings reporting the relationship between aortic valve sclerosis and clinical outcome, and proposes a definition of aortic valve sclerosis based on the literature.
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Affiliation(s)
- S Michael Gharacholou
- Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA
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Ngo DTM, Stafford I, Sverdlov AL, Qi W, Wuttke RD, Zhang Y, Kelly DJ, Weedon H, Smith MD, Kennedy JA, Horowitz JD. Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations. Br J Pharmacol 2011; 162:722-732. [PMID: 20958293 PMCID: PMC3041260 DOI: 10.1111/j.1476-5381.2010.01084.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2010] [Revised: 09/19/2010] [Accepted: 09/25/2010] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND AND PURPOSE Aortic valve stenosis (AVS) is associated with significant cardiovascular morbidity and mortality. To date, no therapeutic modality has been shown to be effective in retarding AVS progression. We evaluated the effect of angiotensin-converting enzyme inhibition with ramipril on disease progression in a recently developed rabbit model of AVS. EXPERIMENTAL APPROACH The effects of 8 weeks of treatment with either vitamin D₂ at 25,000 IU for 4 days a week alone or in combination with ramipril (0.5 mg·kg⁻¹) on aortic valve structure and function were examined in New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)) and aortic valve:outflow tract flow velocity ratio were utilized to quantify changes in valve structure and function. KEY RESULTS Treatment with ramipril significantly reduced AV(BS) and improved aortic valve :outflow tract flow velocity ratio. The intravalvular content of the pro-oxidant thioredoxin-interacting protein was decreased significantly with ramipril treatment. Endothelial function, as measured by asymmetric dimethylarginine concentrations and vascular responses to ACh, was improved significantly with ramipril treatment. CONCLUSIONS AND IMPLICATIONS Ramipril retards the development of AVS, reduces valvular thioredoxin-interacting protein accumulation and limits endothelial dysfunction in this animal model. These findings provide important insights into the mechanisms of AVS development and an impetus for future human studies of AVS retardation using an angiotensin-converting enzyme inhibitor.
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Affiliation(s)
- Doan TM Ngo
- Department of Medicine, Vascular Disease and Therapeutics Research Group, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of AdelaideSouth Australia, Australia
| | - Irene Stafford
- Department of Medicine, Vascular Disease and Therapeutics Research Group, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of AdelaideSouth Australia, Australia
| | - Aaron L Sverdlov
- Department of Medicine, Vascular Disease and Therapeutics Research Group, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of AdelaideSouth Australia, Australia
| | - Weier Qi
- Department of Medicine, St Vincent's Hospital, University of MelbourneVictoria, Australia
| | - Ronald D Wuttke
- Department of Medicine, Vascular Disease and Therapeutics Research Group, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of AdelaideSouth Australia, Australia
| | - Yuan Zhang
- Department of Medicine, St Vincent's Hospital, University of MelbourneVictoria, Australia
| | - Darren J Kelly
- Department of Medicine, St Vincent's Hospital, University of MelbourneVictoria, Australia
| | - Helen Weedon
- Rheumatology Unit, Repatriation Hospital, Flinders UniversitySouth Australia, Australia
| | - Malcolm D Smith
- Rheumatology Unit, Repatriation Hospital, Flinders UniversitySouth Australia, Australia
| | - Jennifer A Kennedy
- Department of Medicine, Vascular Disease and Therapeutics Research Group, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of AdelaideSouth Australia, Australia
| | - John D Horowitz
- Department of Medicine, Vascular Disease and Therapeutics Research Group, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of AdelaideSouth Australia, Australia
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Blaha MJ, Budoff MJ, Rivera JJ, Khan AN, Santos RD, Shaw LJ, Raggi P, Berman D, Rumberger JA, Blumenthal RS, Nasir K. Relation of aortic valve calcium detected by cardiac computed tomography to all-cause mortality. Am J Cardiol 2010; 106:1787-91. [PMID: 21055710 DOI: 10.1016/j.amjcard.2010.08.019] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2010] [Revised: 08/11/2010] [Accepted: 08/11/2010] [Indexed: 10/18/2022]
Abstract
Aortic valve calcium (AVC) can be quantified on the same computed tomographic scan as coronary artery calcium (CAC). Although CAC is an established predictor of cardiovascular events, limited evidence is available for an independent predictive value for AVC. We studied a cohort of 8,401 asymptomatic subjects (mean age 53 ± 10 years, 69% men), who were free of known coronary heart disease and were undergoing electron beam computed tomography for assessment of subclinical atherosclerosis. The patients were followed for a median of 5 years (range 1 to 7) for the occurrence of mortality from any cause. Multivariate Cox regression models were developed to predict all-cause mortality according to the presence of AVC. A total of 517 patients (6%) had AVC on electron beam computed tomography. During follow-up, 124 patients died (1.5%), for an overall survival rate of 96.1% and 98.7% for those with and without AVC, respectively (hazard ratio 3.39, 95% confidence interval 2.09 to 5.49). After adjustment for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking, and a family history of premature coronary heart disease, AVC remained a significant predictor of mortality (hazard ratio 1.82, 95% confidence interval 1.11 to 2.98). Likelihood ratio chi-square statistics demonstrated that the addition of AVC contributed significantly to the prediction of mortality in a model adjusted for traditional risk factors (chi-square = 5.03, p = 0.03) as well as traditional risk factors plus the presence of CAC (chi-square = 3.58, p = 0.05). In conclusion, AVC was associated with increased all-cause mortality, independent of the traditional risk factors and the presence of CAC.
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Relation between progression of aortic valve sclerosis and carotid intima-media thickening in asymptomatic subjects with cardiovascular risk factors. J Echocardiogr 2010; 8:87-93. [PMID: 27278799 DOI: 10.1007/s12574-010-0038-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2009] [Revised: 02/01/2010] [Accepted: 02/04/2010] [Indexed: 10/19/2022]
Abstract
BACKGROUND Aortic valve sclerosis (AVS) is the early lesion of calcific aortic valve disease and may subsequently progress toward valvular stenosis. Histopathological and clinical evidence has suggested that AVS and atherosclerosis share similar mechanisms. However, little is known regarding the relation between the early AVS progression and the early atherosclerosis progression. The carotid intima-media thickness (IMT) by carotid ultrasonography has been established as the surrogate marker of the early atherosclerosis. The aim of this study was to examine the association between progression of early AVS and increase of carotid IMT. METHODS We retrospectively analyzed the data of 127 asymptomatic subjects (49 ± 8 years, 114 men) with ≥1 cardiovascular (CV) risk factors, without history of CV disease, who underwent echocardiographic and carotid ultrasonographic examinations twice ≥6 months apart. We evaluated aortic valve morphology and function and carotid IMT at the baseline and at follow-up examinations. RESULTS During a follow-up of 25 ± 15 months, the number of subjects with AVS was significantly increased (34 vs. 47%, P < 0.0001) and the mean value of carotid IMT was significantly increased (1.16 ± 0.33 vs. 1.29 ± 0.41 mm, P < 0.0001). The progression of AVS was observed in 26 subjects. By logistic regression analysis, the baseline carotid IMT value was an independent predictor of AVS progression (odds ratio = 4.07, P = 0.026). CONCLUSION In asymptomatic subjects with CV risk factors, progression of AVS and increase of carotid IMT were observed during a mean follow-up period of 25 months. Progression of AVS in asymptomatic subjects with CV risk factors was associated with carotid intima-media thickening.
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Losi MA, Brevetti G, Schiano V, Barbati G, Parisi V, Contaldi C, Chiacchio E, Cavallaro M, Carpinella G, Fundaliotis A, Parrella LS, Betocchi S, Brevetti L, Chiariello M. Aortic Valve Sclerosis in Patients with Peripheral and/or Coronary Arterial Disease. Echocardiography 2010; 27:608-12. [DOI: 10.1111/j.1540-8175.2009.01109.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
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Cai Q, Serrano R, Kalyanasundaram A, Shirani J. A preoperative echocardiographic predictive model for assessment of cardiovascular outcome after renal transplantation. J Am Soc Echocardiogr 2010; 23:560-6. [PMID: 20381999 DOI: 10.1016/j.echo.2010.03.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2009] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Major adverse cardiac events (MACE) frequently determine the outcome of renal transplantation (RT). Stress testing is advocated for preoperative risk assessment, but limited information is available on the prognostic value of these tests. We aimed to retrospectively assess the value of preoperative dobutamine stress echocardiography (DSE) in predicting MACE in patients undergoing RT. METHODS A total of 185 patients (age 56 +/- 11 years, 64% were men, creatinine level of 7.3 +/- 2.9 mg/d, 27% were smokers, 86% had hypertension, 54% had diabetes, 57% were dyslipidemic) with end-stage renal disease (ESRD) underwent DSE before RT. A standard DSE protocol was used with the administration of 5-50 mug/kg/min incremental doses in 3-minute intervals and up to 1 mg of atropine if needed to reach prespecified end points. RESULTS Regional left ventricular wall motion abnormality (WMA) at rest (fixed), with stress (inducible), or both were present in 54, 35, and 18 patients, respectively. In 38 patients who underwent coronary angiography, the sensitivity, specificity, and positive and negative predictive values of inducible WMA for predicting angiographic coronary artery disease (> or = 70% luminal diameter reduction) were 88%, 62%, 65%, and 87%, respectively. Cox regression analysis identified the presence of combined fixed and inducible WMA (ie, resting WMA that did not change during DSE, accompanied by new WMA evident during DSE; hazard ratio [HR] 5.6, P = .012), left atrial enlargement (HR 4.2, P = .002), and aortic valve sclerosis (HR 3.9, P = .013) as independent predictors of 48-month MACE (cardiac death, nonfatal acute myocardial infarction, and coronary revascularization after RT). Patients with all 3 predictors had a 48-month MACE of 60% compared with 5% in those with none (P = .007). Compared with those without WMA, patients with both fixed and inducible WMA had a higher rate of MACE at 48 months (7% vs 33%, P = .004). CONCLUSION In RT candidates, DSE can effectively identify those at low and high risk of MACE.
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Affiliation(s)
- Qiangjun Cai
- Department of Internal Medicine, Geisinger Medical Center, Danville, Pennsylvania 17822, USA
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Ngo DT, Sverdlov AL, Willoughby SR, Nightingale AK, Chirkov YY, McNeil JJ, Horowitz JD. Determinants of Occurrence of Aortic Sclerosis in an Aging Population. JACC Cardiovasc Imaging 2009; 2:919-27. [DOI: 10.1016/j.jcmg.2009.03.016] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2008] [Revised: 03/09/2009] [Accepted: 03/25/2009] [Indexed: 10/20/2022]
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Abstract
Valve replacement is the only long-term effective treatment for calcific aortic valve stenosis. However, this treatment is aimed only at patients with advanced leaflet disease and symptoms of left ventricular obstruction. Over the past 15 years, our understanding of the pathogenesis of calcific aortic stenosis has changed significantly: away from a passive degenerative disease to an active process involving endothelial dysfunction, lipid accumulation, an inflammatory infiltrate, and a regulated process of calcification. Since many of the same processes are characteristic of atherosclerosis, trials have been undertaken to test whether medical therapy (statins, renin-angiotensin inhibition) can prevent or alter the disease course. Although retrospective and non-randomized studies suggested a positive effect with statins, benefit has not been seen in perspective randomized controlled trials, although two major studies are still in progress. Inhibition of renin-angiotensin has shown discordant results in retrospective studies with no randomized controlled data published. In the future, we need to consider other medical therapies that might target different pathways in this disease process. In addition, we need to define the optimal timing and duration of therapy for this chronic slowly progressive disease; treatments aimed at the early disease process may be ineffective with end-stage tissue changes.
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Affiliation(s)
- Peter J Cawley
- Department of Medicine, University of Washington, Seattle, USA
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Tziomalos K, Athyros VG, Karagiannis A, Mikhailidis DP. Established and emerging vascular risk factors and the development of aortic stenosis: an opportunity for prevention? Expert Opin Ther Targets 2008; 12:809-820. [PMID: 18554150 DOI: 10.1517/14728222.12.7.809] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Aortic stenosis (AS) is the commonest valvular heart disease in the developed world. It is becoming increasingly accepted that the pathogenesis of AS and of its preceding abnormalities, aortic valve sclerosis (AVS) and aortic valve calcification (AVC), shares many characteristics with the atherosclerotic process. OBJECTIVE To assess the contribution of established and emerging vascular risk factors in the development of AS and to evaluate the potential of pharmacological intervention to modify the natural history of AS. METHODS We reviewed the epidemiological data that link AS and atherosclerosis and studies of vasculoprotective agents in patients with AS. RESULTS/CONCLUSIONS AS, AVS and AVC share many common risk factors with atherosclerosis and are possible markers of preclinical vascular disease. Statins appear to delay the progression of AS. However, more studies are needed before introducing such pharmacologic treatment for AS. The future may point towards targeted prevention of AS.
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Affiliation(s)
- Konstantinos Tziomalos
- University College London, Royal Free University College Medical School, Royal Free Hospital, Department of Clinical Biochemistry, Pond Street, London NW3 2QG, UK
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Ngo DTM, Stafford I, Kelly DJ, Sverdlov AL, Wuttke RD, Weedon H, Nightingale AK, Rosenkranz AC, Smith MD, Chirkov YY, Kennedy JA, Horowitz JD. Vitamin D(2) supplementation induces the development of aortic stenosis in rabbits: interactions with endothelial function and thioredoxin-interacting protein. Eur J Pharmacol 2008; 590:290-6. [PMID: 18585377 DOI: 10.1016/j.ejphar.2008.05.051] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2008] [Revised: 04/10/2008] [Accepted: 05/20/2008] [Indexed: 10/22/2022]
Abstract
Understanding of the pathophysiology of aortic valve stenosis (AVS) and finding potentially effective treatments are impeded by the lack of suitable AVS animal models. A previous study demonstrated the development of AVS in rabbits with vitamin D(2) and cholesterol supplementation without any hemodynamic changes in the cholesterol supplemented group alone. The current study aimed to determine whether AVS develops in an animal model with vitamin D(2) supplementation alone, and to explore pathophysiological mechanisms underlying this process. The effects of 8 weeks' treatment with vitamin D(2) alone (n=8) at 25,000 IU/4 days weekly on aortic valve structure and function were examined in male New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)), transvalvular velocity, and transvalvular pressure gradient were utilized to quantitate changes in valve structure and function. Valvular histology/immunochemistry and function were examined after 8 weeks. Changes in valves were compared with those in endothelial function and in valvular measurement of thioredoxin-interacting protein (TXNIP), a marker/mediator of reactive oxygen species-induced oxidative stress. Vitamin D(2) treated rabbits developed AVS with increased AV(BS) (17.6+/-1.4 dB vs 6.7+/-0.8 dB, P<0.0001), increased transvalvular velocity and transvalvular pressure gradient (both P<0.01 via 2-way ANOVA) compared to the control group. There was associated valve calcification, lipid deposition and macrophage infiltration. Endothelial function was markedly impaired, and intravalvular TXNIP concentration increased. In this model, vitamin D(2) induces the development of AVS with histological features similar to those of early AVS in humans and associated endothelial dysfunction/redox stress. AVS development may result from the loss of nitric oxide suppression of TXNIP expression.
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Affiliation(s)
- Doan T M Ngo
- Cardiology Unit, The Queen Elizabeth Hospital, Department of Medicine, The University of Adelaide, Australia
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Mazzone A, Venneri L, Berti S. Aortic valve stenosis and coronary artery disease: pathophysiological and clinical links. J Cardiovasc Med (Hagerstown) 2007; 8:983-9. [DOI: 10.2459/jcm.0b013e32802e6c3d] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Abstract
Elderly patients with valvular aortic stenosis have an increased prevalence of coronary risk factors, of coronary artery disease, and evidence of other atherosclerotic vascular diseases. Statins may reduce the progression of aortic stenosis (AS). Angina pectoris, syncope or near syncope, and congestive heart failure are the 3 classic manifestations of severe AS. Prolonged duration and late peaking of an aortic systolic ejection murmur best differentiate severe AS from mild AS on physical examination. Doppler echocardiography is used to diagnose the prevalence and severity of AS. The indications for cardiac catheterization and the medical management of AS are discussed. Once symptoms develop, aortic valve replacement (AVR) should be performed in patients with severe or moderate AS. Other indications for AVR are discussed. Warfarin should be administered indefinitely after AVR in patients with a mechanical aortic valve and in patients with a bioprosthetic aortic valve who have either atrial fibrillation, prior thromboembolism, left ventricular systolic dysfunction, or a hypercoagulable condition. Patients with a bioprosthetic aortic valve without any of these 4 risk factors should be treated with aspirin 75-100 mg daily.
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Affiliation(s)
- Wilbert S Aronow
- Cardiology Division, Department of Medicine, New York Medical College, Valhalla, New York 10595, USA.
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Ho J, FitzGerald S, Cannaday J, Stolfus L, Weilbacher D, Henderson Y, Newman T, Whitehead R, Radford N. Relation of aortic valve calcium to myocardial ischemic perfusion in individuals with a low coronary artery calcium score. Am J Cardiol 2007; 99:1535-7. [PMID: 17531576 DOI: 10.1016/j.amjcard.2007.01.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2006] [Revised: 01/10/2007] [Accepted: 01/10/2007] [Indexed: 11/20/2022]
Abstract
The absence of coronary artery calcium (CAC) is associated with minimal atherosclerosis. Nonetheless, morbid and mortal cardiovascular events occur in patients with low CAC. This study attempts to identify whether calcific deposits outside the coronary arteries or traditional cardiovascular risk variables are associated with myocardial ischemia in patients with low CAC scores. From 1998 to 2006, a total of 605 patients with an Agatston CAC score of 0 to 10 were referred for stress echocardiography or myocardial perfusion imaging. There was a low rate (1.2%) of myocardial ischemia. Seven of 303 patients (2.3%) had ischemia on perfusion imaging. Zero of 302 stress echocardiograms were abnormal. Traditional risk-factor analysis did not predict the presence of ischemia. No differences in age, gender, or self-reported hyperlipidemia, diabetes mellitus, tobacco use, hypertension, or family history of premature heart disease were noted. Contrary to previous belief, patients with myocardial ischemia were not younger or female. Aortic valve calcium (AVC) was associated with ischemia (p = 0.02), with a >10-fold likelihood of having ischemia detected by MPS versus those without AVC (20.0% vs 1.7%). In conclusion, a CAC score <10 is associated with a low rate of myocardial ischemia. AVC may identify a subset of patients who may be at higher risk.
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Affiliation(s)
- John Ho
- Cooper Clinic, Dallas, Texas, USA.
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Shah SJ, Ristow B, Ali S, Na BY, Schiller NB, Whooley MA. Acute myocardial infarction in patients with versus without aortic valve sclerosis and effect of statin therapy (from the Heart and Soul Study). Am J Cardiol 2007; 99:1128-33. [PMID: 17437741 PMCID: PMC2778470 DOI: 10.1016/j.amjcard.2006.11.057] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2006] [Revised: 11/27/2006] [Accepted: 11/27/2006] [Indexed: 10/23/2022]
Abstract
Aortic sclerosis is associated with cardiovascular events in patients without coronary heart disease (CHD), but it is unclear whether this association exists in patients with established CHD or is independent of baseline cardiac disease severity. It is also unclear whether statins modify this association. In a prospective cohort study of 814 outpatients with established CHD and no evidence of aortic stenosis, the association of aortic sclerosis with subsequent cardiovascular events was examined using a multivariable Cox proportional hazards model. Of 814 participants, 324 (40%) had aortic sclerosis. During 4 years of follow-up, 10% with aortic sclerosis experienced a myocardial infarction (MI) compared with 5% of those without aortic sclerosis (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.1 to 3.1, p = 0.02). This association was unchanged after adjustment for potential confounders and mediators (HR 2.4, 95% CI 1.3 to 4.8, p = 0.009). However, the association between aortic sclerosis and MI appeared to differ by statin use (p = 0.15 for interaction). Aortic sclerosis predicted subsequent MI in subjects not administered statins (adjusted HR 4.1, 95% CI 1.1 to 15.7, p = 0.04), but not in those administered statins (adjusted HR 1.7, 95% CI 0.8 to 3.9, p = 0.18). In conclusion, aortic sclerosis was present in 40% of patients with CHD and is independently associated with a 2.4-fold increased rate of subsequent MI. Statins may attenuate the increased risk of future MI in patients with aortic sclerosis.
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Affiliation(s)
- Sanjiv J Shah
- Division of Cardiology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
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Messika-Zeitoun D, Bielak LF, Peyser PA, Sheedy PF, Turner ST, Nkomo VT, Breen JF, Maalouf J, Scott C, Tajik AJ, Enriquez-Sarano M. Aortic Valve Calcification. Arterioscler Thromb Vasc Biol 2007; 27:642-8. [PMID: 17185617 DOI: 10.1161/01.atv.0000255952.47980.c2] [Citation(s) in RCA: 154] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background—
Aortic valve calcification (AVC) is considered degenerative. Recent data suggested links to atherosclerosis or coronary disease (CAD).
Methods and Results—
AVC and coronary artery calcifications (CAC) were prospectively assessed by Electron-Beam-Computed-Tomography in 262 population-based research participants ≥60 years. AVC was frequent (27%) with aging (
P
<0.01) and in men (
P
<0.05). AVC was associated with diabetes, hypertension, higher body-mass-index, and serum glucose (all
P
<0.05). AVC was a marker of higher prevalence (
P
<0.01) and severity of CAD (CAC score: 441±802 versus 265±566,
P
<0.05) independently of age. After follow-up of 3.8±0.9 years, AVC score increased (94±271 versus 54±173,
P
<0.01, +11±32 U/year), faster with higher baseline AVC score (
P
<0.01). Compared with participants remaining free of AVC, de novo acquisition of AVC was associated with higher LDL-cholesterol (141±31 versus 121±27 mg/dL,
P
<0.05) and faster CAC progression (+78±87 versus +28±47 U/year,
P
<0.05). In multivariate analysis, LDL-cholesterol independently determined AVC acquisition while higher baseline AVC scores determined faster progression of existing AVC.
Conclusion—
In the population, AVC is frequent with aging and atherosclerotic risk factors. AVC is a marker of subclinical CAD. AVC is progressive, appearing de novo with progressive atherosclerosis whereas established AVC progresses independently of atherosclerotic risk factors and faster with increasing initial AVC loads.
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Affiliation(s)
- David Messika-Zeitoun
- Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
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Aronow WS. Aortic stenosis. COMPREHENSIVE THERAPY 2007; 33:174-183. [PMID: 18025609 DOI: 10.1007/s12019-007-8021-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2007] [Revised: 11/30/1999] [Accepted: 07/16/2007] [Indexed: 10/22/2022]
Abstract
Patients with aortic stenosis (AS) have an increased prevalence of coronary risk factors, coronary artery disease, and other atherosclerotic vascular disease and an increased incidence of coronary events and death. Statins may reduce the progression of AS. Angina pectoris, syncope or near syncope, and heart failure are the three classic manifestations of severe AS. Prolonged duration and late peaking of an aortic systolic ejection murmur best differentiate severe AS from mild AS on physical examination. Doppler echocardiography is used to diagnose the presence and severity of AS. Once symptoms develop, aortic valve replacement (AVR) should be performed in patients with severe or moderate AS. Warfarin should be administered indefinitely after AVR in patients with a mechanical aortic valve and in patients with a bioprosthetic aortic valve who have either atrial fibrillation, prior thromboembolism, left ventricular systolic dysfunction, or a hypercoagulable condition. Patients with a bioprosthetic aortic valve without any of these four risk factors should be treated with aspirin 75-100 mg daily.
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Affiliation(s)
- Wilbert S Aronow
- Depatment of Medicine, Divisions of Cardiology, Geriatrics, and Pulmonary/Critical Care, New York Medical College, Macy Pavilion, Room 138, Valhalla, NY 10595, USA.
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