ABSTRACT
Cardiovascular disease remains the major cause of worldwide morbidity and mortality. Its pathophysiology is complex and multifactorial. Because the phenotype of cardiovascular disease often shows a marked heritable pattern, it is likely that genetic factors play an important role. In recent years, large genome-wide association studies have been conducted to decipher the molecular mechanisms underlying this heritable and prevalent phenotype. The emphasis of this review is on the recently identified 17 susceptibility loci for coronary artery disease. Implications of their discovery for biology and clinical medicine are discussed. A description of the landscape of human genetics in the near future in the context of next-generation sequence technologies is provided at the conclusion of this review.
Subject(s)
Base Sequence , Coronary Artery Disease/genetics , Genetic Loci , Genetic Predisposition to Disease , Coronary Artery Disease/metabolism , Gene Expression , Genome-Wide Association Study , Homeostasis/genetics , Humans , Lipid Metabolism/genetics , Phenotype , Polymorphism, Single NucleotideABSTRACT
OBJECTIVE: We investigated the effectiveness of statins in daily practice in reducing the arterial wall thicknesses by comparing the carotid intima-media thickness (cIMT) between statin-treated familial hypercholesterolemia (FH) patients and their unaffected spouses. METHODS: FH subjects treated with LDL-c lowering medication for at least 5 years and their unaffected spouses were included in this observational study. Clinical data and carotid intima-media thickness (cIMT) as surrogate marker for atherosclerosis were acquired. RESULTS: In total 40 FH patients, age 48.4±4.2 years, and their 40 unaffected spouses, age 47.4±3.9 years, were included. Pre-treatment total cholesterol levels of FH patients were on average 9.3±2.0 mmol/L. Treated FH patients and unaffected spouses exhibited similar LDL-c (3.8±1.5 vs. 3.5±1.1 mmol/L; p=0.25) and total cholesterol levels (5.8±1.6 vs. 5.6±1.1 mmol/L; p=0.56). Also, in a multivariate model cIMT adjusted for age and sex did not differ between affected and spouses (95% CI: -0.032 to 0.092 mm; p=0.34). CONCLUSION: Long-term statin treatment normalizes cIMT in severe FH patients and therefore it is likely that the extreme risk of cardiovascular disease in FH patients is significantly reduced by this therapy.
