19 research outputs found
1082-184 Gender differrences in the risk factors contributing to carotid intima-media thickness: The Johns Hopkins sibling study
Prevalence of atherogenic LDL pattern B in asymptomatic middle aged African Americans with a family history of premature coronary heart diseases
Elevated C-reactive protein in high-risk asymptomatic individuals is strongly associated with the metabolic syndrome
LDL particle concentration and insulin level predict carotid atheroeclerosis in high risk patients
Prevalence of atherogenic LDL pattern B in asymptomatic middle aged African Americans with a family history of premature coronary heart diseases
Native Platelet Aggregation and Response to Aspirin in Persons With the Metabolic Syndrome and Its Components
Moderate coronary calcification is common in women with a family history of premature coronary disease but a low global risk score
Moderate coronary calcification is common in women with a family history of premature coronary disease but a low global risk score
KLOTHO Allele Status and the Risk of Early-Onset Occult Coronary Artery Disease
We previously identified a functional variant of KLOTHO (termed “KL-VS”), which harbors two amino acid substitutions in complete linkage disequilibrium and is associated with reduced human longevity when in homozygosity. Klotho-deficient mice display extensive arteriosclerosis when fed a normal diet, suggesting a potent genetic predisposition. To determine whether klotho influences atherosclerotic risk in humans, we performed cross-sectional studies to assess the association between the KL-VS allele and occult coronary artery disease (CAD) in two independent samples of apparently healthy siblings of individuals with early-onset (age <60 years) CAD (SIBS-I [N=520] and SIBS-II [N=436]). Occult CAD was defined as the occurrence of a reversible perfusion defect during exercise thallium scintigraphy and/or as an abnormal result of an exercise electrocardiogram (SIBS-I, n=97; SIBS-II, n=56). In SIBS-I, the KL-VS allele conferred a relative odds of 1.90 (95% confidence interval 1.21–2.98) for occult CAD, after adjusting for familial intraclass correlations (P<.005). Logistic regression modeling, incorporating known CAD risk factors, demonstrated that the KL-VS allele is an independent risk factor (P<.019) and that the imposed risk of KL-VS allele status is influenced by modifiable risk factors. Hypertension (P<.022) and increasing high-density lipoprotein cholesterol (HDL-C) levels (P<.022) mask or reduce the risk conferred by the KL-VS allele, respectively, whereas current smoking (P<.004) increases the risk. Remarkably concordant effects of the KL-VS allele and modifying factors on the risk of occult CAD were seen in SIBS-II. These results demonstrate that the KL-VS allele is an independent risk factor for occult CAD in two independent high-risk samples. Modifiable risk factors, including hypertension, smoking status, and HDL-C level, appear to influence the risk imposed by this allele