The aim of this study was to examine whether the well-established effect of the common TaqIB polymorphism in intron 1 of the gene for cholesterol ester transfer protein (CETP) on high density lipoprotein cholesterol (HDL-C) concentration and increased risk of myocardial infarction (MI), could be explained by the recently identified -629C>A functional polymorphism in the promoter. Non-fatal MI cases (388 male) and a control group of 794 healthy men were recruited from the 30 year long prospective Reykjavik Study. In the healthy men the frequency of the TaqIB B2 allele was 0.47 (95% CI: 0.44-0.50) and there was a strong allelic association with the -629A allele (D=-0.21, P
The promoter sequence variant -480T in the hepatic lipase gene (LIPC) has been shown to be significantly associated with low post-heparin hepatic lipase activity. Some studies have also found that the -480T variant is associated with elevation in plasma HDL cholesterol. We tested for associations of LIPC -480T with plasma lipoprotein traits in samples taken from three distinct Canadian populations: 657 Alberta Hutterites, 328 Ontario Oji-Cree and 210 Keewatin Inuit. Plasma HL activity was not available for analyses. The LIPC -480T allele frequencies in these three groups, respectively, were 0.219, 0.527 and 0.383, and the prevalence of LIPC -480T/T homozygotes was, respectively, 0.042, 0.274 and 0.167. No significant association was found between LIPC -480T and plasma HDL cholesterol or apolipoprotein AI concentration, after adjusting for covariates including gender and body mass index. There was no consistent relationship between the population mean plasma HDL cholesterol concentration and the population LIPC -480T frequency. Our findings are consistent with the idea that the common promoter variation in LIPC, which has been reported to be associated with variation in post heparin HL activity and HDL triglyceride concentration, is not always associated with variation in plasma HDL cholesterol concentration, possibly due to yet unspecified environmental or genetic factors.
Fibrinogen (FBG) and total coagulation factor VII (FVIIc) concentrations are higher in those patients with coronary artery disease who are at increased future risk of acute ischemic events. The relationship between activated factor VII (FVIIa) and cardiovascular events, however, has not been intensively studied. Data were collected from 401 consecutive patients who underwent coronary angiography because of suspected coronary artery disease. Conventional risk factors FVIIc, FVIIa and FBG were assessed in relation to the severity of coronary artery disease, left ventricular ejection fraction, and previous clinical events. A strong positive correlation was found between FVIIa and FVIIc (p
OBJECTIVES: To investigate the interplay between use of alcohol, concentration of low density lipoprotein cholesterol, and risk of ischaemic heart disease. DESIGN: Prospective study with controlling for several relevant confounders, including concentrations of other lipid fractions. SETTING: Copenhagen male study, Denmark. SUBJECTS: 2826 men aged 53-74 years without overt ischaemic heart disease. MAIN OUTCOME MEASURE: Incidence of ischaemic heart disease during a six year follow up period. RESULTS: 172 men (6.1%) had a first ischaemic heart disease event. There was an overall inverse association between alcohol intake and risk of ischaemic heart disease. The association was highly dependent on concentration of low density lipoprotein cholesterol. In men with a high concentration (> or = 5.25 mmol/l) cumulative incidence rates of ischaemic heart disease were 16.4% for abstainers, 8.7% for those who drank 1-21 beverages a week, and 4.4% for those who drank 22 or more beverages a week. With abstainers as reference and after adjustment for confounders, corresponding relative risks (95% confidence interval) were 0.4 (0.2 to 1.0; P or = 3.63 mmol/l who abstained from drinking alcohol was 43% (10% to 64%). CONCLUSIONS: In middle aged and elderly men the inverse association between alcohol consumption and risk of ischaemic heart disease is highly dependent on the concentration of low density lipoprotein cholesterol. These results support the suggestion that use of alcohol may in part explain the French paradox.
Comment In: ACP J Club. 1996 Sep-Oct;125(2):51
Comment In: BMJ. 1996 Aug 10;313(7053):365-68760765
The effects on blood lipids and blood pressure of a diet corresponding to present Nordic Nutrition Recommendations, i.e. less than 30% of energy from fat and with a fibre content exceeding 3 g/MJ, were studied in 18 men and 12 women (mean age, 24 years) under strict dietary control over 8 months. Blood sampling, blood pressure and body weight measurement were performed at four occasions on their habitual diet and once a month during the intervention period. An age-matched control group (17 men, 8 women) was followed with monthly measurements parallel to the intervention group. The habitual diets, assessed by 7-day records, showed an average fat content corresponding to 36% of energy. Initial levels of total cholesterol and HDL cholesterol (X +/- SD) were 4.21 +/- 0.61 and 1.23 +/- 0.23 mmol/l for the men in the intervention group; 4.35 +/- 0.79 and 1.21 +/- 0.26 mmol/l for the male controls; 4.61 +/- 0.59 and 1.46 +/- 0.31 mmol/l for the women in the intervention group and 4.48 +/- 0.64 and 1.48 +/- 0.29 mmol/l for the female controls. Significantly decreased levels of total cholesterol and HDL cholesterol throughout the experimental period were seen for both sexes in the intervention group. Total cholesterol fell 0.49 mmol/l (95% CI: 0.41-0.56) in the male subjects and 0.49 mmol/l (95% CI: 0.39-0.59) in the female subjects. The fall in HDL cholesterol was 0.16 mmol/l (95% C: 0.13-0.18) and 0.18 mmol/l (95% CI: 0.12-0.23), respectively. Total cholesterol changes were independent of initial values. All subjects were normotensive at the start of the study with an average blood pressure of 122/68 mmHg for men and 112/68 mmHg for the women. Systolic blood pressure dropped gradually and significantly in the male subjects of the intervention group. A minimum of 6 mmHg below initial values was noted after six months of dietary intervention. No significant changes in dietary intake and blood lipids were observed in the control group. Thus, changes of present dietary habits of young healthy Danish subjects to an intake in accordance with the Nordic Nutrition Recommendations 1989 will favourably affect suggested risk factors for disease.
AIMS: to examine the incidence rate of progression to Type 2 diabetes and baseline prognostic risk factors, focusing on hypertension and antihypertensive medication, in a cohort (n=207) with impaired glucose tolerance (IGT). METHODS: after 2 and 4.6 (1. 9-6.4) years new cases of diabetes were diagnosed by the oral glucose tolerance test (OGTT). Hypertension (BP 160/95 or antihypertensive medication) was included in multiple regression analyses to assess the effect of risk factors on the development of diabetes. RESULTS: diabetes developed in 32 subjects (19%), an incidence of 41/1000 (95% CI 28-57/1000) person-years. In univariate analyses, progression to diabetes was associated with a high (>9.0 mmol/l) 2-h OGTT value (P=0.008), a high fasting insulin (>12.0 mU/l) level (P=0.000), a high triglyceride (>/=1.3 mmol/l) level (P=0.028), a high BMI (>/=28.0 kg/m(2)) (P=0.013) and hypertension (P=0.003). The risk for the development of diabetes was not increased in hypertensive subjects without antihypertensive medication compared with normotensive subjects (OR 0.8, 95% CI 0.3-2. 6). However, it was increased in subjects with on medication, especially diuretics alone or in combination with other drugs. Hypertensive subjects on diuretics had higher levels of fasting insulin and triglycerides and higher BMIs at baseline than normotensive subjects. After adjustment for 2-h OGTT, fasting insulin, triglycerides and BMI, the OR for diabetes was 7.7 (95% CI 2.1-28.2) in hypertensive subjects using diuretics alone or in combination with other drugs and 2.6 (95% CI 1.0-6.7) in those using other drugs compared with normotensive subjects. The OR of diabetes corresponding to a one-unit increase in the 2-h OGTT concentration was 2.5 (95% CI 1.6-4.0) in the whole cohort. CONCLUSIONS: the rate of progression from IGT to Type 2 diabetes in this population was similar to that seen in other studies among Caucasian populations. The use of antihypertensive medication, especially diuretics, and a high 2-h OGTT level were significant predictors of subsequent deterioration to diabetes.
Apolipoprotein A-IV (apoA-IV) is a glycoprotein constituent of triglyceride-rich and high-density lipoproteins (HDL) and may thus play an important role in lipid metabolism. In Finland two common isoforms (A-IV-1 and A-IV-2) of apoA-IV have been found. The isoforms are the result of the G to T substitution in the third base of the codon 360 in the apoA-IV-2 allele of the apoA-IV gene. The purpose of the study was to determine the apoA-IV allele frequencies in the Saami and the Finns, and to relate the apoA-IV phenotypes to serum lipids. The sample was drawn in connection with a Reindeer Herders' Health Survey performed in northern Finland in 1989. The study group included 248 men with known ethnic origin, Saami and Finns, who lived in the area of the nine northernmost municipalities of Finland. ApoA-IV phenotypes from 71 Saami (both parents Saami) and 177 Finns (both parents Finns) were determined by isoelectric focusing and Western blotting. Serum lipids were determined enzymatically. ApoA-IV allele frequencies in the Saami and the Finns were for A-IV-1 0.894 vs 0.944 and for A-IV-2 0.106 vs 0.056, respectively (chi2-test, P
Automated methods for the determination of apolipoprotein B and apolipoprotein A-I were developed, tested, and applied in screening programs of large populations to improve information about the composition and degree of hyperlipoproteinemia. Apolipoproteins B and A-I, total cholesterol, and triglyceride levels were measured in 25,659 males and 18,144 females between 20 and 79 years of age, the majority subjectively healthy. The immunoturbidimetric methods used for apolipoproteins B and A-I were shown to be stable over time, and the errors of the methods were below 7%. Apolipoprotein B correlated with total cholesterol (r = 0.86, P less than 0.001) for each age decile group and for both sexes (r = 0.82-0.87, P less than 0.001). For a subsample comparable to the large population, apolipoprotein B correlated with cholesterol in low density (i.e., the atherogenic particle), r = 0.89, P less than 0.001. The mean values for apolipoprotein B increased with age for both sexes, with much higher levels in males than in females under 50 years of age. Apolipoprotein A-I was lower in males than in females in all age-groups. At all cholesterol levels males had higher apolipoprotein B, and at the same triglyceride level, also lower apolipoprotein A-I and hence a higher B/A-I ratio than females. Using apolipoprotein B and A-I (high-density lipoprotein cholesterol) particles and adopting Swedish consensus criteria for the diagnosis of risk of ischemic heart disease, examples are given showing that many individuals, especially females, with high or borderline total serum cholesterol can be excluded from further investigation/treatment for hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS)
In a previous report, a large regional variation was reported in total mortality and mortality rate from ischaemic heart disease (IHD) in mid-Sweden. In this report, IHD prevalence and risk factor data are presented. A postal questionnaire was sent out to a random sample of men aged 45-64 years in each of 40 communities. 14,675 men (88%) responded. Based on a validity study, IHD cases were defined as those with a history of myocardial infarction and/or angina pectoris. Age, smoking habits, antihypertensive treatment, body mass index, food habits, stress and physical activity during leisure time were used as risk factors. IHD prevalence showed the same geographical variation as IHD mortality, with a low prevalence in the east and a high prevalence in the west. There was a moderate variation in risk factor levels over the 40 communities. When this variation was taken into account the geographical IHD variation was somewhat smaller but still substantial. Other factors may involve socio-economics, drinking water qualities, mineral soil content or other environmental factors. Which of these cause the largest IHD variation is at present unknown, but is subject to systematic examination in this project.
BACKGROUND. High blood pressure has been associated with elevated atherogenic blood lipid fractions, but epidemiological surveys often give inconsistent results across population subgroups. A better understanding of the relation between blood pressure and blood lipids may provide insight into the mechanism(s) whereby hypertension is associated with increased risk of coronary heart disease. METHODS AND RESULTS. We assessed the cross-sectional relations of serum total cholesterol, high density lipoprotein (HDL) cholesterol, non-HDL cholesterol (total minus HDL cholesterol), and triglyceride levels with blood pressure in a population of 8,081 men 20-54 years old and 7,663 women 20-49 years old. Stratified analyses and multivariable methods were used to control for potential confounding anthropometric and lifestyle variables. Total and non-HDL cholesterol levels increased significantly with increasing systolic or diastolic blood pressure in both sexes. Men 20-29 years old had steeper regression slopes for blood pressure by total cholesterol level than did women of similar age. In men, the association between blood pressure and total cholesterol level decreased with age, whereas in women, it increased with age. Body mass index modified the relation, whereas smoking, physical activity, and alcohol consumption had little influence on the association. Triglyceride levels increased with blood pressure, but this relation was weak in lean subjects. HDL cholesterol level correlated positively with blood pressure in population subgroups having a high alcohol consumption. CONCLUSION. These results support the hypothesis that there are biological interrelations between blood pressure and blood lipids that may influence the mechanisms whereby blood pressure is associated with risk of coronary heart disease.