Oestrogen receptor alpha gene polymorphism is related to aortic valve sclerosis in postmenopausal women.

OBJECTIVES: Aortic valvular sclerosis (AS) is an inflammatory process and not a result of normal ageing. The sclerotic process is accelerated by risk factors such as smoking and high cholesterol levels. The genetic factors for the development of AS are however unknown. Therefore the purpose of the present study was to investigate whether polymorphisms in the oestrogen receptor alpha (ORalpha) gene and in the transforming growth factor beta (TGF-beta1) gene were related to the presence of AS in postmenopausal women. DESIGN: Case-control study. SUBJECTS AND METHODS: Relationships were tested between polymorphisms in the ORalpha gene defined by the restriction enzymes PvuII and XbaI, and in the TGF-beta1 gene defined by AocI, and AS, lipid levels, and lipoprotein(a) [Lp(a)] in 41 postmenopausal female patients and 41 age- and sex-matched controls. These polymorphisms were also tested in relation to lipid levels and Lp(a), in 99 healthy Caucasian girls, aged 16.9 +/- 1.2 years. RESULTS: In the postmenopausal patients and age-matched controls, the PvuII polymorphism was independently associated with an increased risk of AS [odds ratio (OR) = 3.38; 95% confidence interval (CI) 1.13-10.09). A genotype defined by at least one restriction site in the PvuII polymorphism and two restriction sites in the TGF-beta1 polymorphism was related to a highly significantly increased risk of AS (OR = 4.58; 95% CI 1.68-12.51). In the adolescent female cohort, presence of two restriction sites in the PvuII polymorphism was associated with higher levels of total cholesterol (TC) (P = 0.02), and low-density lipoprotein cholesterol (LDL) (P = 0.04). CONCLUSIONS: We have demonstrated that the PvuII polymorphism in the ORalpha gene is related to both the presence of AS in postmenopausal women and to lipid levels in adolescent females, suggesting that this polymorphism may influence the risk of AS partly by affecting lipid levels.

Is lipoprotein(a) a predictor for survival in patients with established coronary artery disease? Results from a prospective patient cohort study in northern Sweden.

OBJECTIVES: Lipoprotein(a) [Lp(a)] is a known risk factor for the development of atherosclerosis. The aim of the present study was to test the importance of Lp(a) as a predictor for the further prognosis in patients with established coronary artery disease. DESIGN: A prospective patient cohort study was carried out. SETTING AND SUBJECTS: The cohort consists of 1216 patients who were examined with coronary angiography at the University Hospital in Umeå, Sweden, because of stable effort angina. MAIN OUTCOME MEASURES: Lipids, Lp(a), fibrinogen, antithrombin III (AT III), sedimentation rate and clinical data were registered at angiography. After a mean follow-up time of 6.7 years information on survival was collected from the municipal census lists and death certificates were examined. Total mortality and mortality because of cardiovascular disease were both used as outcome variables in the survival analyses. RESULTS. The total mortality in the patient cohort was 16.4%. An Lp(a) level of 300 mg L-1 or more was found in 30% of the study population and was found to be an independent predictor for death. A high fibrinogen, a low AT III level, a depressed left ventricular function and a high coronary obstruction score were other significant independent predictors of death. Total cholesterol, HDL- and LDL-cholesterol were not related to survival in this study, but a substantial proportion of the population probably received lipid-lowering agents during the study period. CONCLUSIONS: An Lp(a) level exceeding 300 mg L-1 indicates a poor further prognosis and may help to identify patients who probably need powerful secondary prevention programmes to improve their prognosis.