Apolipoprotein E polymorphism and C-reactive protein in dyslipidemic middle-aged men.
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Apolipoproteins E↗
Biomedical subjects
V Manninen
Publications and source records attributed to V Manninen.
Joint effects of C-reactive protein and other risk factors on acute coronary events.
BACKGROUND: Elevated serum C-reactive protein (CRP) is a predictor of coronary heart disease in population samples. We studied the contribution of the simultaneous presence (joint effects) of elevated CRP and the classic as well as some new risk factors on acute coronary events. METHODS: With a nested case-control design and logistic regression analyses, we measured baseline and pre-event CRP levels in patients who had myocardial infarction or coronary death (cases) during an 8.5-year follow-up in the Helsinki Heart Study, a coronary primary prevention trial in dyslipidemic middle-aged men. The control patients were participants remaining free of coronary events. RESULTS: Baseline and pre-event CRP levels were higher in cases than in control patients (4.4 vs 2.0 mg/L, P <.001 and 6.0 vs 3.6 mg/L, P <.001). The relative risk attributed to elevated CRP was 40% higher with chronic elevation (odds ratio [OR], 3.34) compared with high baseline (OR, 2.24) or pre-event (OR, 2.26) level only. Hypertension, low high-density lipoprotein cholesterol, and high leukocyte count increased the risk only marginally without simultaneous occurrence of high CRP, whereas the joint effects of CRP and these classic risk factors suggested additive effects on coronary risk. In contrast, high levels of immunoglobulin G-class antibodies to oxidized low-density lipoprotein and antiprothrombin antibodies as well as high total immunoglobulin G level increased the risk irrespective of CRP. CONCLUSIONS: Elevated CRP enhances the risks attributed to classic coronary risk factors.
Adult↗
Infections, inflammation, and the risk of coronary heart disease.
BACKGROUND: The role of infections and inflammation in the pathophysiology of coronary heart disease is emerging. We studied the independent and joint effects of these 2 components on coronary risk. METHODS AND RESULTS: We measured baseline levels of C-reactive protein (CRP) and antibodies to adenovirus, enterovirus, cytomegalovirus, and herpes simplex virus as well as to Chlamydia pneumoniae (Cpn) and Helicobacter pylori in 241 subjects who suffered either myocardial infarction or coronary death during the 8.5-year trial in the Helsinki Heart Study, a coronary primary prevention trial. The 241 controls in this nested case-control study were subjects who completed the study without coronary events. Antibody levels to herpes simplex type I (HSV-1) and to Cpn were higher in cases than in controls, whereas the distributions of antibodies to other infectious agents were similar. Mean CRP was higher in cases (4.4 versus 2.0 mg/L; P<0.001), and high CRP increased the risks associated with smoking and with high antimicrobial antibody levels. The odds ratios in subjects with high antibody and high CRP levels were 25.4 (95% CI 2.9-220.3) for HSV-1 and 5.4 (95% CI 2.4-12.4) for Cpn compared with subjects with low antibody levels and low CRP. High antibody levels to either HSV-1 or to Cpn increased the risk independently of the other, and their joint effect was close to additive. CONCLUSIONS: Two chronic infections, HSV-1 and Cpn, increase the risk of coronary heart disease. The effect is emphasized in subjects with ongoing inflammation, denoted by increased CRP levels.
Adult↗
Joint effects of an aldosterone synthase (CYP11B2) gene polymorphism and classic risk factors on risk of myocardial infarction.
BACKGROUND: The -344C allele of a 2-allele (C or T) polymorphism in the promoter of the gene encoding aldosterone synthase (CYP11B2) is associated with increased left ventricular size and mass and with decreased baroreflex sensitivity, known risk factors for morbidity and mortality associated with myocardial infarction (MI). We hypothesized that this polymorphism was a risk factor for MI. METHODS AND RESULTS: We used a nested case-control design to investigate the relationships between this polymorphism and the risk of nonfatal MI in 141 cases and 270 matched controls from the Helsinki Heart Study, a coronary primary prevention trial in dyslipidemic, middle-aged men. There was a nonsignificant trend of increasing risk of MI with number of copies of the -344C allele. However, this allele was associated in a gene dosage-dependent manner with markedly increased MI risk conferred by classic risk factors. Whereas smoking conferred a relative risk of MI of 2.50 (P=0.0001) compared with nonsmokers in the entire study population, the relative risk increased to 4.67 in -344CC homozygous smokers (relative to nonsmokers with the same genotype, P=0.003) and decreased to 1.09 in -344TT homozygotes relative to nonsmokers with this genotype. Similar joint effects were noted with genotype and decreased HDL cholesterol level as combined risk factors. CONCLUSIONS: Smoking and dyslipidemia are more potent risk factors for nonfatal MI in males who have the -344C allele of CYP11B2.
Adult↗
Prediction of myocardial infarction in dyslipidemic men by elevated levels of immunoglobulin classes A, E, and G, but not M.
BACKGROUND: Immune mechanisms have been suggested to play an important role in the development of coronary atherosclerosis and its thrombotic complications. We evaluated the predictive value of the levels of various serum immunoglobulin classes in middle-aged men at increased risk of myocardial infarction. METHODS: Using nested case-control design and logistic regression analysis, we estimated the association between serum immunoglobulins and the risk of coronary end points (nonfatal or fatal myocardial infarction or sudden cardiac death) in dyslipidemic men (levels of non-high-density lipoprotein cholesterol >5.2 mmol/L [>201 mg/dL]) participating in the Helsinki Heart Study. The cases consisted of 135 subjects in whom a coronary end point occurred during the 5-year observation period of the study, and the controls were 135 subjects who did not suffer coronary end points during this period. Levels of IgA, IgE, IgG, and IgM were determined in serum samples collected at study entry. RESULTS: Levels of IgA, IgE, and IgG, but not IgM, were significantly higher in cases than in controls. After adjustment for other risk factors, such as age, smoking, and blood pressure, the risk of coronary disease showed a significant relation to the levels of IgA, IgE, and IgG. The risk in the highest quartile of each distribution as compared with the lowest quartile was 2.2-fold for IgA (95% confidence interval, 1.0-4.5), 2.8-fold for IgE (1.3-5.9), and 2.8-fold for IgG (1.3-5.9). Hypertriglyceridemia and a low level of high-density lipoprotein cholesterol were associated with increased risk of a coronary end point only if the levels of IgA, IgE, or IgG were also elevated. CONCLUSION: Elevated levels of IgA, IgE, and IgG are associated with myocardial infarction and cardiac death in men with dyslipidemia. The present data suggest that, for dyslipidemia to cause coronary atherothrombosis, an immune response reflected by elevated levels of these immunoglobulin classes is an important determinant.
Adult↗
Antibodies to prothrombin crossreact with plasminogen in patients developing myocardial infarction.
In a prospective study on healthy middle-aged men, high level of antibodies to prothrombin implied a risk of myocardial infarction. The possible mechanism(s) of these antibodies in coronary thrombosis are not known. Because prothrombin belongs to the kringle proteins and shares structural homology with a fibrinolytic kringle protein plasminogen, we studied whether antibodies to prothrombin crossreact with plasminogen. Sera from 17 healthy middle-aged men who later developed myocardial infarction were studied. Binding of antibodies to immobilized prothrombin (EIA) was inhibited by using soluble prothrombin, plasminogen and synthetic peptides of 20 amino acids from plasminogen kringle 5 (P304, P305) and from prothrombin kringle 2 (P302) as inhibitors. The peptides contained the conserved pentapeptide CRNPD of the kringle proteins. Soluble prothrombin inhibited up to 50% the binding of antibodies to immobilized prothrombin in all sera. Plasminogen inhibited binding in 9/17 (53%) sera (a decrease of at least 20%). P305 inhibited binding to prothrombin in 8/17 (47%), P304 in 4/17 (23%) and P302 in 6/17 (35%) sera. In structural analysis, presentation of the pentapeptide was conformationally different between the peptides. We conclude that crossreactive antibodies binding to prothrombin and plasminogen occur in sera of patients later developing myocardial infarction. The crossreactive epitope seems to be conformational and include the conserved pentapeptide of the kringle proteins. These antibodies may interfere with the fibrinolytic function of plasminogen and contribute to the development of myocardial infarction.
Antibodies↗
A study to determine the response of coronary atherosclerosis to raising low high density lipoprotein cholesterol with a fibric-acid derivative in men after coronary bypass surgery. The rationale, design, and baseline characteristics of the LOCAT Study. Lopid Coronary Angiography Trial.
Several clinical trials have shown that reducing serum cholesterol levels retards the progression of coronary atherosclerosis assessed by serial angiography. By contrast, as yet no studies have addressed the impact of increasing high density lipoprotein (HDL) cholesterol levels on progression of coronary artery disease (CAD). As HDL cholesterol is inversely related to the risk of CAD, we hypothesize that an intervention that raises low HDL cholesterol concentrations may have a beneficial effect on the course of CAD. Lopid Coronary Angiography Trial (LOCAT) was designed to test this hypothesis. Three hundred and ninety-five men, aged < or = 70 years, all of whom had previously undergone coronary bypass surgery, were randomly assigned to receive either slow-release gemfibrozil, 1200 mg once daily, or a matching placebo for on average 2 1/2 years. The lipid inclusion criteria were HDL cholesterol concentration < or = 1.1 mmol/L, low density lipoprotein (LDL) cholesterol < or = 4.5 mmol/L, and serum triglyceride < or = 4.0 mmol/L. Subjects were not accepted if they had manifest diabetes, body mass index > 30 kg/m2, uncontrolled hypertension, or if they were regular smokers. All randomized subjects underwent baseline coronary angiography, which will be repeated at the end of the study. The angiograms will be analyzed using the Cardiovascular Measurement System, a validated computer-assisted image-analysis and quantitation package. The primary endpoints are the changes in the per-patient mean of 1) the average diameter of evaluable native coronary segments, and 2) the minimal luminal diameter of evaluable stenoses, and 3) the appearance of new lesions. Extensive lipoprotein and other metabolic studies and analyses of genetic polymorphisms are carried out to study the determinants of CAD progression. At baseline, the study subjects were 59.1 +/- 6.8 (mean +/- standard deviation) years old, had a body mass index 26.4 +/- 2.2 kg/m2, and serum triglyceride, serum cholesterol, HDL cholesterol, and LDL cholesterol concentrations 1.64 +/- 0.64, 5.17 +/- 0.64, 0.82 +/- 0.14, and 3.61 +/- 0.53 mmol/L, respectively.
Cholesterol, HDL↗
Alcohol and coronary heart disease: the roles of HDL-cholesterol and smoking.
OBJECTIVES: To study the role of HDL-cholesterol (HDLc) in the causal pathway mediating the effect of alcohol on coronary heart disease (CHD). DESIGN: Cox proportional hazard models were used to compare the relative CHD risks in various HDLc-smoking categories. SETTING: A prospective, multicentre, placebo-controlled, double-blind CHD primary prevention trial with gemfibrozil in primary (occupational) health care units, the Helsinki Heart Study. SUBJECTS: Dyslipidaemic middle-aged men with available alcohol consumption data (1924 of 2035) in the placebo arm of the 5-year study. MAIN OUTCOME MEASURES: Seventy-seven (of 84) cases of nonfatal myocardial infarction or cardiac death. RESULTS: A U-shaped association was detected between alcohol consumption and CHD. The protection was found both in subjects with low (mean 0.94 mmol L-1) and normal (mean 1.25 mmol L-1) HDLc with corresponding reductions of 23% and 36% in relative risks. In contrast to previous data, alcohol offered virtually no protection against CHD in non-smokers. In subjects consuming more than 800 g pure ethanol annually, the CHD incidence was 6/1000 in subjects with more than three weekly drinking occasions, compared to 11/1000 in 'weekend' drinkers. CONCLUSIONS: Our results confirm the protective effect of alcohol against CHD. However, in contrast to previous data the effect in our population is restricted to smokers and the role of HDLc in mediating the effect is less central than suggested previously.
Adult↗
QT dispersion as a risk factor for sudden cardiac death and fatal myocardial infarction in a coronary risk population.
OBJECTIVE: To test in a prospective study the hypothesis that increased QT dispersion in resting 12-lead ECG is a predictor of sudden cardiac death. DESIGN: A nested case-control study during a mean (SD) follow up time of 6.5 (2.8) years. SETTING: A prospective, placebo controlled, coronary prevention trial with gemfibrozil among dyslipidaemic middle aged men in primary (occupational) health care units: the Helsinki heart study. PATIENTS: 24 victims of fatal myocardial infarction, 48 victims of sudden cardiac death without acute myocardial infarction, and their matched controls. MAIN OUTCOME MEASURES: QT dispersion in baseline and pre-event electrocardiograms. RESULTS: At study baseline, QT dispersion was similar in all victims and controls. When estimated from the pre-event ECG on average 14 months before death, the risk of sudden cardiac death in the highest QTPEAK (up to the peak of the T wave) dispersion tertile (> or = 50 ms) was 6.2-fold (95% confidence interval 1.7 to 23.5) compared with the risk in the lowest tertile (< or = 30 ms), and 4.9-fold (1.2 to 19.5) after adjustment for the presence of left ventricular hypertrophy, while QTPEAK dispersion could not predict fatal myocardial infarction. QTEND dispersion (up to the end of the T wave) in pre-event ECGs could not discriminate victims of either sudden cardiac death or fatal myocardial infarction from their matched controls. CONCLUSIONS: In middle aged men with a normal conventional QT interval in 12-lead resting ECG, increased QTPEAK dispersion is an independent risk factor for sudden cardiac death, but not for fatal myocardial infarction.
Adult↗
How to define coronary heart disease in register-based follow-up studies: experience from the Helsinki Heart Study.
Information on coronary heart disease (CHD) obtained from the Finnish Hospital Discharge and Cause-of-Death Registers was compared with that collected in the Helsinki Heart Study (HHS) during an 8.5-year follow-up. The purpose of the comparison was two-fold, firstly, to study the accuracy of registration of CHD and secondly, to find out what diagnostic codes to use for CHD in register-based follow-up studies. The HHS cases were used as the 'golden standard' and the CHD deaths and definite nonfatal acute myocardial infarctions (AMIs) (all diagnoses) were taken from the registers to establish the sensitivity of the Hospital Discharge and Cause-of-Death Registers combined. The sensitivity was 0.84 during the period 1980-86 and 0.87 during 1987-90, with the positive predictive values 0.94 and 0.92 respectively. The treatment effects seen in the HHS were compared with the effects that would have emerged, if register-based information only had been used with different definitions of CHD. Of the register-based calculations, the one with the definition 'all CHD deaths and hospitalizations with the ICD-8 code 410' came closest to the HHS result, with a 32% reduction (P=0.028 one-sided) of CHD incidence, while the original HHS result was a 34% reduction (P=0.008 one sided). However, when comparing Kaplan-Meier plots of cumulative hazards of CHD, the plot with a wider definition of CHD (ICD-8 and ICD-9 codes 410-414) came closest to the HHS experience, especially if revascularizations were included in the latter. Definite AMI as a single definition of CHD might thus not be sufficient when studying CHD risk, instead, at least two parallel definitions of CHD should be used.
Coronary Disease↗
Antibodies to prothrombin imply a risk of myocardial infarction in middle-aged men.
Antiphospholipid antibodies in patients with "antiphospholipid syndrome" may be directed at least in part against plasma phospholipid-binding proteins, such as beta 2-glycoprotein I or prothrombin, which are involved in the control of thrombosis and haemostasis. IgG-class antibodies against prothrombin and beta 2-glycoprotein I were measured by enzyme-linked immunoassay in initially healthy middle-aged dyslipidaemic men (non-high-density lipoprotein > 5.2 mml/l). Serum samples had been drawn at entry to a 5-year coronary primary-prevention trial with gemfibrozil from 106 subjects who experienced either a non-fatal myocardial infarction or cardiac death during the follow-up and from 106 subjects without coronary episodes, matched for treatment group (gemfibrozil/placebo) and geographical area. The antiprothrombin antibody level, as expressed in optical density units, was significantly higher in patients than in controls (0.26 +/- 0.17 versus 0.22 +/- 0.09; p < 0.02). A high level of antiprothrombin antibodies (highest tertile of distribution) predicted a 2.5-fold increase in the risk (95% confidence interval 1.2-5.3) of myocardial infarction or cardiac death. The distribution of IgG-class antibodies against beta 2-glycoprotein I did not differ significantly between cases and controls. The joint effect of antiprothrombin antibodies and other factors associated with hypercoagulative state: triglyceride level, lipoprotein(a) and smoking, was multiplicative for the risk. Antiprothrombin antibodies are a new immunological predictor of myocardial infarction and the effect of these antibodies may be mediated by hypercoagulative mechanisms.
Apolipoproteins↗
Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil. Experience from the Helsinki Heart Study.
BACKGROUND: Coronary risk factors related to the insulin resistance syndrome tend to cluster in the same individual. Our previous studies have shown that the dyslipidemia characteristic of this syndrome--low HDL cholesterol and high triglyceride (TG) levels--responds well to treatment with gemfibrozil. Most factors related to insulin-resistance syndrome decrease fibrinolytic capacity, whereas a recent study showed that gemfibrozil improves it and thus may attenuate thrombotic events. To discover whether subjects with clustering of factors related to this resistance might in particular benefit from gemfibrozil, we reanalyzed the Helsinki Heart Study data. METHODS AND RESULTS: We used Cox regression models to explore the effects of gemfibrozil among overweight subjects with additional coronary risk factors in this hypercholesterolemic male population of 2046 subjects randomized to gemfibrozil and 2035 to placebo. The effect of gemfibrozil was largely confined to overweight subjects: among those with body mass index (BMI) > 26 kg/m2, the net difference in cardiac end points between gemfibrozil and placebo groups was 21 (25 of 1119 versus 46 of 1081), and in those with BMI < or = 26 kg/m2, it was 7 (31 of 927 versus 38 of 954). The risk reduction with gemfibrozil was 78% (P = .002) among those with BMI > 26 kg/m2 and dyslipidemia (TG > or = 2.3 mmol/L and HDL cholesterol < 1.08 mmol/L). Among those with BMI > 26 kg/m2 and three or four of the following factors present--smoking, sedentary lifestyle, blood pressure > or = 140/90 mm Hg, or blood glucose > 4.4 mmol/L--the risk reduction was 68% (P = .03). CONCLUSIONS: Gemfibrozil reduced the coronary risk mainly in overweight subjects with additional risk factors known to contribute to the insulin-resistance syndrome or predispose to it.
Adult↗
Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men.
BACKGROUND: Data concerning the relation between antiphospholipid (aPL) antibodies and myocardial infarction in subjects without evidence of overt autoimmune disease are conflicting. All published studies have been performed on survivors of myocardial infarction or in patients with established coronary heart disease. The purpose of the present study was to determine whether the presence of aPL antibodies, namely, anti-cardiolipin (aCL) antibodies, carries a risk for myocardial infarction in a prospective cohort. METHODS AND RESULTS: The sera to be studied were drawn at entry from middle-aged dyslipidemic men (non-high-density lipoprotein cholesterol, > or = 5.2 mmol/L) participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil. Samples were tested for IgG-class antibodies to cardiolipin by an ELISA. The risk was estimated with logistic regression analysis using a nested case-control design with 133 patients (myocardial infarction or cardiac death) and 133 control subjects, matched for treatment (gemfibrozil/placebo) and geographical area. The aCL antibody level, as expressed in optical density units, was significantly higher in patients than in control subjects (0.417 versus 0.361; P < .005). Subjects with the antibody level in the highest quartile of distribution had a relative risk for myocardial infarction of 2.0 (95% confidence interval, 1.1 to 3.5) compared with the remainder of the population. This risk was independent of confounding factors, such as age, smoking, systolic blood pressure, low-density lipoprotein (LDL), and high-density lipoprotein. There was a correlation between the levels of aCL antibodies and antibodies to oxidized LDL (r = .40, P < .001), and their joint effect was additive for the risk. CONCLUSIONS: In a prospective cohort of healthy middle-aged men, the presence of a high aCL antibody level is an independent risk factor for myocardial infarction or cardiac death. Antibodies to cardiolipin and oxidized LDL may, at least in part, represent cross-reactive antibody populations.
Antibodies, Anticardiolipin↗
Antihypertensive therapy in dyslipidemic men. Effects on coronary heart disease incidence and total mortality.
To investigate the influence of antihypertensive therapy and the success of blood pressure control on coronary heart disease incidence and total mortality, we studied dyslipidemic middle-aged men participating in the placebo arm of the Helsinki Heart Study, a randomized coronary primary prevention trial with gemfibrozil. Based on blood pressure level and the presence of antihypertensive therapy at study entry, the participants were classified into four categories. Relative risks of coronary heart disease (nonfatal myocardial infarction or cardiac death) and total mortality during the 5-year trial period were calculated using Cox proportional hazards models. With subjects who were not using antihypertensive drugs and who had normal blood pressure (category I) as reference, the relative risks of coronary heart disease during the trial period were 2.1 (95% confidence interval [CI], 1.3 to 3.3) in untreated hypertensive subjects (category II), 0.9 (95% CI, 0.2 to 3.8) in subjects with successful antihypertensive therapy (category III), and 2.0 (95% CI, 1.0 to 4.1) in subjects who remained hypertensive despite drug therapy (category IV). The relative risks of death were 1.9 (95% CI, 0.9 to 3.9) in category II and 1.0 (95% CI, 0.1 to 7.3) in category III; in category IV subjects, those with unsuccessful antihypertensive therapy, the relative risk was 4.4 (95% CI, 2.0 to 9.6). The excess mortality in this category was due to cardiovascular causes and was clustered in subjects with multiple drug therapy for hypertension control. We conclude that successful antihypertensive therapy in dyslipidemic men reduced coronary heart disease incidence despite its adverse effects on high-density lipoprotein cholesterol and triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)
Antihypertensive Agents↗
Effects of hypertension and dyslipidemia on the decline in renal function.
Experimental evidence suggests that in addition to hypertension, serum lipids might also accelerate the decline in renal function. We tested this hypothesis in 2702 dyslipidemic middle-aged men without renal disease participating in the Helsinki Heart Study, a coronary primary prevention trial. The decline in renal function was estimated from linear regression slopes based on reciprocals of 10 serum creatinine determinations over the study period. Renal function deteriorated 3% on average during the 5-year study, and hypertension accelerated this change. Subjects with an elevated ratio of low- to high-density lipoprotein cholesterol ( > 4.4) had a 20% faster decline than those with a ratio less than 3.2. Both the contribution of the lipoprotein ratio and the protective effect of high-density lipoprotein cholesterol alone remained significant in multiple regression analyses. In the study of joint effects the contribution of lipids was confined to subjects with simultaneous elevation of blood pressure and lipids. The results suggest that in addition to hypertension, blood lipids also modify the decline in renal function.
Adult↗
Hypofibrinolysis and increased lipoprotein (a) coincide in stroke.
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Cerebrovascular Disorders↗
Antibody against oxidized low-density lipoprotein predicting myocardial infarction.
BACKGROUND: Oxidation of low-density lipoprotein is believed to be an important step in the pathogenesis of atherosclerosis. The purpose of the present study was to determine whether antibody against oxidized low-density lipoprotein, reported to be associated with the progression of carotid atherosclerosis, is predictive of cardiac death and nonfatal myocardial infarction. METHODS: Serum samples from 135 cases and their controls, drawn at entry from middle-aged dyslipidemic men participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil, were tested for immunoglobulin G class antibodies against oxidized low-density lipoprotein by enzyme-linked immunosorbent assay. RESULTS: The mean antibody level, expressed in optical density units, was significantly higher in cases than in controls (0.412 vs 0.356, P = .002). After adjustment for age, smoking, blood pressure, and high-density lipoprotein cholesterol level, there was a 2.5-fold increased risk (95% confidence interval, 1.3 to 4.9) of a cardiac end point in the highest tertile of antibody level vs the lowest tertile (P = .005 for trend). CONCLUSIONS: Elevated levels of antibodies against oxidized low-density lipoprotein were predictive of myocardial infarction. The effect was independent of low-density lipoprotein cholesterol levels, and the joint effect was additive. Elevated antibody levels modified the effects of classic coronary risk factors.
Adult↗
Adrenal androgens and testosterone as coronary risk factors in the Helsinki Heart Study.
We investigated the role of adrenal androgens, cortisol, testosterone and sex-hormone binding globulin (SHBG) as coronary risk factors using a nested case-control design. The study population consisted of 62 cases with cardiac end-points and 97 controls on placebo during the last 4 years in the Helsinki Heart Study. Serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, androstanediol glucuronide, cortisol, testosterone, and SHBG at the first annual visit of the 5-year study period were determined by radioimmunoassays. The only significant difference was found in DHEAS, with cases having higher levels than controls (P < 0.04). DHEAS levels were positively associated with smoking (P < 0.001), alcohol consumption (P < 0.04) and triglyceride levels (P < 0.002) and with systolic (P < 0.04) and diastolic (P < 0.006) blood pressures, and negatively associated with age (P < 0.01) and HDL-cholesterol (P < 0.03). The association between DHEAS and the CHD risk was studied using logistic regression analyses with the classical risk factors--age, smoking, blood pressure, and lipid levels--as covariates in the models. Studies of the joint effects of age and DHEAS disclosed that the risk associated with elevated DHEAS was confirmed to older men (odds ratio (OR) 7.3, 95%, CI 2.3-23.3). A similar analysis with smoking revealed that the DHEAS-related risk was mainly found in smokers (OR 3.4, 95% CI 1.5-8.2). One possible explanation for these results is that some form of mild steroid biosynthetic defect of the adrenals or functional adrenal hyperplasia associated with high DHEAS levels increases the CHD risk in this population.
Adrenal Glands↗