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Determinants of Occurrence of Aortic Sclerosis in an Aging Population

Doan T.M. Ngo, BPharm, PhD^_*, Aaron L. Sverdlov, MBBS^_*, Scott R. Willoughby, PhD^_*, Angus K. Nightingale, MD^_*, Yuliy Y. Chirkov, PhD^_*, John J. McNeil, MBBS, PhD, John D. Horowitz, MBBS, PhD^_*,_*

^_* University of Adelaide, South Australia, Australia
Monash University, Victoria, Australia

^_* Reprint requests and correspondence: Dr. John D. Horowitz, Cardiology Unit, The Queen Elizabeth Hospital, University of Adelaide, 28 Woodville Road, Woodville South, South Australia, 5011 (Email: john.horowitz{at}adelaide.edu.au).

Objectives: We sought to identify clinical, physiological, and biochemical correlates, including markers of endothelial dysfunction and of tissue nitric oxide (NO) responsiveness, of the presence of aortic sclerosis (ASc) in an aging population.

Background: Aortic sclerosis has been regarded predominantly as a precursor of hemodynamically significant aortic stenosis. However, ASc also represents an independent correlate of increased risk of cardiovascular morbidity and mortality; the basis of this association is incompletely understood. The assumption that the pathogenesis of aortic valve disease is similar to that of atherosclerosis has not been supported by recent studies; rather there has been increasing evidence of a pathogenetic role of inflammation and endothelial dysfunction. Furthermore, we have recently developed methodology for echocardiographic quantitation of early aortic valve disease.

Methods: Randomly selected subjects (n = 253) ages 51 to 77 years underwent transthoracic echocardiography; aortic valve ultrasonic backscatter score (AV_BS) was used to quantitate echogenicity of the aortic valve. Conventional coronary risk factors were identified. Integrity of NO generation/response was assessed via: 1) plasma asymmetric dimethylarginine concentrations, as a marker of endothelial dysfunction; 2) inhibition of platelet aggregation by the NO donor sodium nitroprusside, as a measure of tissue NO responsiveness and also a coronary prognostic marker; and 3) aortic augmentation index, as a measure of arterial stiffness/wave reflection. All putative correlations with AV_BS were examined by univariate and multiple linear regression analyses.

Results: On the basis of AV_BS scores, ASc was present in 19.4% of subjects. The AV_BS directly correlated with patients' age but inversely correlated with high-sensitivity C-reactive protein, creatinine clearance, and platelet NO responsiveness. On multiple linear regression, ASc was associated with impaired platelet NO responsiveness (β = –0.16, p = 0.02), advancing age (β = 0.21, p = 0.003), and low body mass index (β = –0.23, p = 0.001).

Conclusions: Aortic sclerosis is associated with platelet NO resistance rather than conventional coronary risk factors: this might explain the increased thrombotic risk in ASc.

Key Words: aging • aortic valve sclerosis • endothelial function • nitric oxide • platelets

Abbreviations and Acronyms   2D = 2-dimensional   ACEI = angiotensin-converting enzyme inhibitor   ADMA = asymmetric dimethylarginine   AIIRB = angiotensin II receptor blocker   AIx = augmentation index   AS = aortic stenosis   ASc = aortic sclerosis   AVBS = aortic valve ultrasonic backscatter score   BMI = body mass index   BSA = body surface area   CrCl = creatinine clearance   CRP = C-reactive protein   hs-CRP = high-sensitivity C-reactive protein   LDL = low-density lipoprotein (cholesterol)   LV = left ventricular   NO = nitric oxide   SNP = sodium nitroprusside

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