Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Cardiac & Cardiovascular Systems, Cardiovascular System & Cardiology, 1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, Cardiovascular System & Hematology, 3201 Cardiovascular medicine and haematology, 3202 Clinical sciences

Abstract:

Background: Carotid-femoral pulse wave velocity (PWV) is a well validated marker of arterial stiffness and of subsequent cardiovascular outcome measures. It is unknown whether genetic variants on the 9p21 locus, which confer a major risk for atherosclerotic cardiovascular morbidity and mortality, are related to arterial stiffness in the general population. Methods: The prospective Asklepios study is a random sample (n=2524 apparently healthy volunteers) from the Belgian general population, free from overt cardiovascular disease. The subjects were extensively screened, including genotyping of the rs1333049 variation on 9p21 and screening for subclinical atherosclerotic lesions in the carotid and femoral arteries. PWV was measured using Doppler echography in the femoral and carotid arteries. Results: In a multivariable analysis, adjusting for age, smoking, systolic blood pressure, heart rate, total and HDL-cholesterol, obesity, glycemia, high-sensitive c-reactive protein, physical activity, fruit and vegetable intake, educational achievement and drug therapies (lipid-lowering, antihypertensive), the rs1333049 at-risk C-allele was significantly and independently associated with PWV (F=4.6; p=0.032). Per C-allelle, PWV increased by 0.074 (95%CI: 0.007 – 0.142) m/s. In post-hoc analyses, the association between rs1333049 and PWV was restricted to subjects with detectable atherosclerosis (intima-media thickening and/or plaque). In subjects with atherosclerosis PWV increases by 0.126 – 0.226 m/s per copy of the at-risk C-allele of rs13333049. Interpretation: These are the first results linking the 9p21 locus to arterial stiffness in a random population sample. 9p21 impacts arterial stiffness through shared pathways with atherosclerosis.