Risk Factors Associated With Calcification of the Aortic Valve

The purpose of this study is

• to determine the degree of endothelial dysfunction and inflammation in calcific aortic valve disease associated with coronary artery disease(CAD).
• to determine whether there is relationship between calcium metabolism and calcific aortic valve disease associated with CAD.

Cardiovascular disease, mainly coronary artery disease, causes more than one half of deaths in the developed countries. Only recently, calcific aortic valve disease, was proved to belong to the family of atherosclerosis. It is associated with higher cardiovascular morbidity and mortality, the cause of which is not entirely clear. The link to significant coronary artery disease, probably, is of highest importance.

We compare groups of patients with coronary artery disease and calcific stenotic, sclerotic or intact aortic valve. The aim is to assess and compare their risk profile to verify our hypothesis that, within significant coronary artery disease, calcific aortic valve identifies a subgroup of patients with higher cardiovascular risk, assessed by endothelial dysfunction and the two year follow-up of cardiovascular events on optimally set treatment.

Further, we study the possible association of valvular calcification and calcium metabolism in patients with normal kidney function.

Consecutive patients admitted to hospital for evaluation due to common causes like dyspnea, chest pain, fatigue or syncope, who fulfilled the two inclusion criteria: 1/ angiographically significant CAD, and 2/ AS (mean transvalvular aortic gradient ≥30 mm Hg) or nonobstructive aortic sclerosis (mean gradient ≤10 mmHg) or had normal aortic valve as diagnosed by echocardiography.

• Aortic Stenosis
• Aortic Sclerosis

• 1
  Patients with aortic stenosis (mean transvalvular aortic gradient ≥30 mm Hg) plus angiographically significant coronary artery disease (more than 50% diameter stenosis)
• 2
  Patients with nonobstructive aortic sclerosis (mean gradient ≤10 mmHg) plus angiographically significant coronary artery disease (more than 50% diameter stenosis)
• 3
  Patients with normal aortic valve plus angiographically significant coronary artery disease (more than 50% diameter stenosis)

• Linhartová K, Veselka J, Sterbáková G, Racek J, Topolcan O, Cerbák R. Parathyroid hormone and vitamin D levels are independently associated with calcific aortic stenosis. Circ J. 2008 Feb;72(2):245-50.
• Linhartová K, Filipovský J, Cerbák R, Sterbáková G, Hanisová I, Beránek V. Severe aortic stenosis and its association with hypertension: analysis of clinical and echocardiographic parameters. Blood Press. 2007;16(2):122-8.
• Ferda J, Linhartová K, Kreuzberg B. Comparison of the aortic valve calcium content in the bicuspid and tricuspid stenotic aortic valve using non-enhanced 64-detector-row-computed tomography with prospective ECG-triggering. Eur J Radiol. 2007 Oct 23; [Epub ahead of print]
• Linhartová K, Beránek V, Sefrna F, Hanisová I, Sterbáková G, Pesková M. Aortic stenosis severity is not a risk factor for poststenotic dilatation of the ascending aorta. Circ J. 2007 Jan;71(1):84-8.

Inclusion criteria:

• significant stenosis (more than 50% diameter stenosis) of one or more coronary arteries
• aortic sclerosis (group 1) or stenosis (AVA < 1cm2/m2, or mean gradient ≥ 30 mmHg) (group 2) or normal aortic valve (group 3)

Exclusion criteria:

• Rheumatic heart disease (defined as aortic stenosis with commissural fusion + rheumatic mitral valve disease)
• Status post aortic valve replacement
• Congenital complex heart disease (except bicuspid aortic valve)
• Moderate to severe aortic insufficiency (grade > 2/4)
• Marfan syndrome
• Infective endocarditis
• Hypertrophic obstruction cardiomyopathy
• Acute coronary syndrome within less than three months
• Severe heart failure, NYHA class IV
• Severe locomotion disability
• Renal failure requiring dialysis
• Significant systemic disease or other disease severely limiting the patient prognosis (e.g. known cancer, liver cirrhosis)
• Primary hyperparathyroidism
• Patient non-compliance