Lipoprotein(a) [Lp(a)] is an important risk factor for cardiovascular disease. Alcohol is one of the few nongenetic factors that lower Lp(a) levels, but the metabolic mechanisms of this action are unknown. Alcohol inhibits the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. Alcohol might also affect IGF-binding protein-1 (IGFBP-1), which is an acute inhibitor of IGF-I. We studied how alcohol withdrawal affects Lp(a) levels and the GH/IGF-I/IGFBP-1 axis. Male alcohol abusers (n=27; 20 to 64 years old) were monitored immediately after alcohol withdrawal for 4 days. Twenty-six healthy men, mainly moderate drinkers, served as control subjects. Fasting blood samples were drawn to determine Lp(a), IGF-I, and IGFBP-1 (by ELISA, RIA, and immunoenzymometric assay, respectively). Nocturnal (12 hours) urine collection was performed in 9 alcoholics and 11 control subjects for GH analyses (RIA). The groups were similar in age and body mass index. Lp(a), GH, and IGF-I tended to be lower and IGFBP-1 higher in the alcoholics immediately after alcohol withdrawal than in the control subjects. During the 4-day observation in alcoholics, Lp(a) levels increased by 64% and IGF-I levels by 41%, whereas IGFBP-1 levels decreased by 59% (P
OBJECTIVE: To investigate the relation between Helicobacter pylori infection and coronary heart disease (CHD). DESIGN: A case-control study. SETTING: Northern Finland (about 650,000 inhabitants). PATIENTS: 116 patients with angiographically documented CHD and 116 controls matched for age and gender randomly recruited from the register of the Finnish Social Insurance Institute. MAIN OUTCOME MEASURES: The odds ratio (OR) estimates for the association of H pylori infection with CHD. RESULTS: 64% of the CHD patients and 53% of the controls were seropositive for H pylori; the OR adjusted for age and gender was 1.5 (95% confidence interval (CI) 0.9 to 2.5). An additional adjustment for the common risk factors of CHD, including lipid concentrations, in a logistic regression analysis produced an OR estimate of 1.1 (95% CI 0.6 to 2.1). Among the controls, those who were H pylori positive had significantly (P = 0.03) higher concentrations of serum triglycerides than those who were H pylori negative: the trend among the cases was similar, but non-significant. The concentrations of HDL cholesterol tended to be lower in those who were H pylori positive than in those who were H pylori negative, among both the cases and the controls. CONCLUSIONS: The impact of H pylori infection as an independent risk factor for CHD seems to be minor. On the other hand the results are consistent with the hypothesis that H pylori infection might modify the serum lipid concentrations in a way that could increase the risk of CHD.
We studied the effect of variation at the lipoprotein lipase (LPL) gene locus on the susceptibility of individuals with Type 2 diabetes mellitus to atherosclerotic vascular disease in a population of 126 male and 114 female patients. The prevalence of any evidence of coronary heart disease (CHD) (presence of ischaemic ECG changes or definite myocardial infarction) was low in the patients who were homozygous for the presence of the PvuII restriction site (genotype 2-2) (40.9%) compared with those who were heterozygous (genotype 1-2) (57.9%; P = 0.05) or homozygous for the absence of it (genotype 1-1) (61.9%; P
OBJECTIVE: To analyse the associations between serum gamma-glutamyl transpeptidase activity (GTP) and the components of the metabolic syndrome. DESIGN: Cross-sectional, observational study of hypertensive patients and controls. SETTING: The participating subjects visited the research laboratory of the Department of Internal Medicine, University of Oulu, Oulu, Finland. SUBJECTS: A total of 1045 Caucasians, 40-59 years of age, consisting of 261 drug-treated hypertensive men, 258 drug-treated hypertensive women and 526 age- and sex-matched controls. MAIN OUTCOME MEASURES: The associations between GTP and the cardiovascular risk factors were analysed through multiple regression and logistic methods and by GTP tertiles. The independent effect of GTP on different insulin measures, calculated from the values of 2 h of oral glucose tolerance test, was estimated after concurrent adjustment for age, obesity and alcohol consumption. RESULTS: GTP correlated highly significantly with the components of the metabolic syndrome. The correlation coefficient were 0.33 between GTP and body mass index, 0. 25 between GTP and systolic blood pressure in control men (P = 0. 0001), 0.39 between GTP and triglycerides, and 0.32 between GTP and fasting insulin in hypertensive women (P = 0.0001). The association between GTP and blood pressure remained significant only at upright measurements in controls. All insulin measures had a significant positive association with increasing GTP tertiles in all the study groups (e.g. fasting insulin 8.1 mU L-1 in the lowest and 11.0 mU L-1in the highest tertile in control women, P = 0.0001), with the exception of fasting insulin in control men. In a pooled logistic analysis after adjustment for age, body mass index, alcohol consumption and gender, the independent predictors of the metabolic syndrome were body mass index, uric acid, total cholesterol and GTP (for log-transformed GTP odds ratio 4.0, 95% CI: 2.80-5.69). CONCLUSIONS: There are significant associations between GTP and the components of the metabolic syndrome. Elevated levels of GTP may not always indicate increased alcohol consumption, but may also suggest the existence of the metabolic syndrome with its subsequent deleterious consequences.
OBJECTIVE: To analyze the relationships between carotid atherosclerosis measured as intima-media thickness (IMT) and different measures of insulin in a population-based case-control study of men and women. RESEARCH DESIGN AND METHODS: Carotid ultrasonographic measurements and 2-h oral glucose tolerance tests were performed in a random sample of 513 hypertensive subjects, aged 40-59 years, and in 518 age- and sex-matched control subjects. The associations between IMT and the different measures of insulin were analyzed through multiple regression and by insulin quintiles. The independent effect of insulin was estimated after concurrent adjustment for age, obesity, LDL cholesterol, and systolic blood pressure. RESULTS: The most powerful correlates with IMT were LDL cholesterol, age, systolic blood pressure, pack-years of smoking, and of the different insulin parameters, 2-h post-load insulin. In stepwise regression analysis, the independent predictors of the mean IMT were LDL cholesterol, systolic blood pressure, pack-years of smoking, and age (P
We compared the risk of acute coronary events in diabetic and non-diabetic persons with and without prior myocardial infarction (MI), stratified by age and sex.
A Finnish MI-register study known as FINAMI recorded incident MIs and coronary deaths (n=6988) among people aged 45 to 74 years in four areas of Finland between 1993 and 2002. The population-based FINRISK surveys were used to estimate the numbers of persons with prior diabetes and prior MI in the population.
Persons with diabetes but no prior MI and persons with prior MI but no diabetes had a markedly greater risk of a coronary event than persons without diabetes and without prior MI. The rate of recurrent MI among non-diabetic men with prior MI was higher than the incidence of first MI among diabetic men aged 45 to 54 years. The rate ratio was 2.14 (95% CI 1.40-3.27) among men aged 50. Among elderly men, diabetes conferred a higher risk than prior MI. Diabetic women had a similar risk of suffering a first MI as non-diabetic women with a prior MI had for suffering a recurrent MI.
Both persons with diabetes but no prior MI, and persons with a prior MI but no diabetes are high-risk individuals. Among men, a prior MI conferred a higher risk of a coronary event than diabetes in the 45-54 year age group, but the situation was reversed in the elderly. Among diabetic women, the risk of suffering a first MI was similar to the risk that non-diabetic women with prior MI had of suffering a recurrent MI.
AIMS/HYPOTHESIS: Ghrelin is a natural growth hormone-releasing peptide thought to be involved in the regulation of energy metabolism. The recent studies concerning the association between ghrelin and insulin-like growth factor-I (IGF-I) concentrations have shown either negative correlation or no correlation at all. The aims of this study were to clarify the association between ghrelin and IGF-I concentrations in a large cohort and to characterize whether obesity, insulin resistance and type 2 diabetes affect this association. METHODS: We analysed fasting plasma ghrelin and IGF-I concentrations of 1,004 middle-aged subjects of the population-based OPERA study. Insulin resistance was estimated using QUICKI. RESULTS: IGF-I concentrations were negatively associated with ghrelin concentrations in the analysis of all subjects before (beta=-0.32, p
Association between high density lipoprotein (HDL) cholesterol concentration and restriction fragment length polymorphisms at the cholesteryl ester transfer protein (CETP) gene locus was studied in a random population-based cohort of 526 Caucasian subjects (259 men, mean age 50.9 years, and 267 women, mean age 51.8 years). HDL cholesterol concentration was adjusted for age, body mass index, alcohol consumption, smoking and plasma triglyceride and low density lipoprotein cholesterol levels. In females, the HDL cholesterol levels were associated with TaqIB polymorphism (1.46 mmol/l in the B1B1 genotype, 1.56 mmol/l in B1B2 and 1.72 mmol/l in B2B2, P = 0.0001 for the trend). In contrast, this was not observed in men (1.24, 1.20, 1.27 mmol/l, NS). The association was seen even in women who were current smokers (1.41, 1.56, 1.75 mmol/l, n = 72, P = 0.007), but not in male smokers (1.26, 1.19, 1.14 mmol/l, n = 102, NS). In male non-smokers the association was weak (1.22, 1.20, 1.32 mmol/l, n = 157, P = 0.05). In postmenopausal women not receiving hormone replacement therapy (n = 108), the association continued to be present, although weaker (1.50, 1.58, 1.70 mmol/l, P = 0.06). CETP activity (n = 101) tended to be lower in subjects with the B2B2 genotype. In conclusion, a clear-cut sex difference was observed in the genotype effect on plasma HDL cholesterol levels. The slight attenuation of the gene dosage effect after menopause suggests that the gender difference may be, at least in part, due to sex hormones. A genetic subgroup (men with the B2B2 genotype) particularly susceptible to the HDL cholesterol decreasing effect of smoking could be demonstrated.