Relative risk for cardiovascular atherosclerotic events after smoking cessation: 6-9 years excess risk in individuals with familial hypercholesterolemia.

Background: Smoking history is often di- or trichotomized into for example "never, ever or current smoking". However, smoking must be treated as a time-dependent covariate when lifetime data is available. In particular, individuals do not smoke at birth, there is usually a wide variation with respect to smoking history, and smoking cessation must also be considered.

Diagnosing familial hypercholesterolaemia: the relevance of genetic testing.

Aims: We assembled a cohort of patients with familial hypercholesterolaemia (FH) for both basic and clinical research. We used a set of established diagnostic criteria to define FH. Some put forward that a definite diagnosis of FH is made when a mutation in the LDL-receptor (LDLR) gene is identified.

Genetic determinants of plasma HDL-cholesterol levels in familial hypercholesterolemia.

The objective of this study was to determine the extent to which common genetic variants can explain the variation of high-density lipoprotein cholesterol (HDL-C) plasma levels in familial hypercholesterolemia (FH). FH is characterized by elevated low-density lipoprotein cholesterol levels and premature cardiovascular disease (CVD). Although low HDL-C levels have been shown to affect the severity of the clinical phenotype, little is known about the factors that determine HDL-C levels in these patients.

Genetic determinants of cardiovascular disease risk in familial hypercholesterolemia.

Objective: To investigate the contribution of polymorphisms in multiple candidate genes to cardiovascular disease (CVD) risk in a large cohort of patients with heterozygous familial hypercholesterolemia (FH).

Methods And Results: We genotyped 1940 FH patients for 65 polymorphisms in 36 candidate genes. During 91.

Guidelines were developed for data collection from medical records for use in retrospective analyses.

Objective: To construct a set of guidelines for data collection from medical records.

Study Design And Setting: Retrospective analysis of clinical data is often performed by physician-scientists. In such research, the source of clinical data is the patient's medical record; however, medical records are intended for patient care and the data are not systematically recorded for research purposes.

Variation at the paraoxonase gene locus contributes to carotid arterial wall thickness in subjects with familial hypercholesterolemia.

Objectives: Paraoxonase (PON1) is a potent enzyme, physically associated with the high-density lipoprotein particle. PON1 may protect against cardiovascular disease (CVD), since it is capable of hydrolyzing oxidized LDL-cholesterol, thereby negating the detrimental effects of this lipoprotein on the arterial wall.

Design And Methods: In 187 patients with familial hypercholesterolemia, we studied the seven most common single nucleotide polymorphisms (SNPs) in both the coding and promoter sequences of PON1 (L55M, Q192R, T-107C, C-126G, G-162A, G-824A, and C-907G) in terms of PON1 activity and intima media thickness (IMT) of the carotid arterial wall, a validated surrogate marker for CVD.

Clinical, diagnostic, and therapeutic aspects of familial hypercholesterolemia.

Heterozygous familial hypercholesterolemia (FH) is a common inherited disorder of lipoprotein metabolism. FH is characterized by elevated levels of low-density lipoprotein cholesterol, the presence of tendon xanthomas, and premature cardiovascular disease. The underlying molecular defect of FH consists of mutations in the gene coding for the low-density-lipoprotein-receptor protein, detection of which provides the only unequivocal diagnosis.

Phenotypic variability in familial hypercholesterolaemia: an update.

Heterozygous familial hypercholesterolaemia is among the most common inherited dominant disorders, and is characterized by severely elevated LDL-cholesterol levels and premature cardiovascular disease. Although the cause of familial hypercholesterolaemia is monogenic, there is a substantial variation in the onset and severity of atherosclerotic disease symptoms. Additional atherogenic risk factors of environmental, metabolic and genetic origin, in conjunction with the LDL receptor defect, are presumed to influence the clinical phenotype in familial hypercholesterolaemia.