Genome-wide mapping of susceptibility to coronary artery disease identifies a novel replicated locus on chromosome 17.

Coronary artery disease (CAD) is a leading cause of death world-wide, and most cases have a complex, multifactorial aetiology that includes a substantial heritable component. Identification of new genes involved in CAD may inform pathogenesis and provide new therapeutic targets. The PROCARDIS study recruited 2,658 affected sibling pairs (ASPs) with onset of CAD before age 66 y from four European countries to map susceptibility loci for CAD. ASPs were defined as having CAD phenotype if both had CAD, or myocardial infarction (MI) phenotype if both had a MI. In a first study, involving a genome-wide linkage screen, tentative loci were mapped to Chromosomes 3 and 11 with the CAD phenotype (1,464 ASPs), and to Chromosome 17 with the MI phenotype (739 ASPs). In a second study, these loci were examined with a dense panel of grid-tightening markers in an independent set of families (1,194 CAD and 344 MI ASPs). This replication study showed a significant result on Chromosome 17 (MI phenotype; p = 0.009 after adjustment for three independent replication tests). An exclusion analysis suggests that further genes of effect size lambda(sib) > 1.24 are unlikely to exist in these populations of European ancestry. To our knowledge, this is the first genome-wide linkage analysis to map, and replicate, a CAD locus. The region on Chromosome 17 provides a compelling target within which to identify novel genes underlying CAD. Understanding the genetic aetiology of CAD may lead to novel preventative and/or therapeutic strategies.

Atorvastatin therapy is associated with reduced levels of N-terminal prohormone brain natriuretic peptide and improved cardiac function in patients with heart failure.

BACKGROUND: Statins have been suggested to improve cardiac function, but the evidence underlying beneficial effects of statins in heart failure (HF) is insufficient. We analyzed plasma N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels and cardiac function in patients with HF of various etiologies, and who were treated with or without statins. HYPOTHESIS: Statin treatment is associated with improved cardiac function in HF. METHODS: The study cohort consisted of 139 consecutive male patients receiving atorvastatin (n = 44), simvastatin (n = 29), pravastatin (n = 19), or no statin (n = 47). The NT-proBNP levels were measured using electroluminescence immunoassay. Left ventricular end-diastolic diameter (LVEDD), fractional shortening (FS), and ejection fraction (EF) were determined by echocardiography. RESULTS: Patients receiving atorvastatin presented with reduced NT-proBNP levels (1,552 +/- 3,416 versus 3,771 +/- 6,763 pg/mL; p < 0.01), and improved values of LVEDD (65.2 +/- 8.9 versus 70.7 +/- 10.9 mm; p < 0.05) and EF (33.2 +/- 12.6 versus 28.2 +/- 9.6%; p < 0.05). By contrast, plasma NT-proBNP and cardiac parameters in patients treated with statins other than atorvastatin did not significantly differ from control. Atorvastatin treatment was equally effective in patients with ischemic and nonischemic HF. CONCLUSIONS: Atorvastatin treatment is associated with improved cardiac function in HF, and may represent an additional option for patients with this disease.

Harmonizing the definition of the metabolic syndrome: comparison of the criteria of the Adult Treatment Panel III and the International Diabetes Federation in United States American and European populations.

The 2 most widely used criteria to diagnose the metabolic syndrome (MS) are those developed by the United States Adult Treatment Panel III of the National Cholesterol Education Program (ATP III) and by the International Diabetes Federation (IDF). A major difference between these 2 sets of criteria is that the IDF places more emphasis on waist circumference. We compared the prevalence of MS using the ATP III and the IDF guidelines in 2 American (the Dallas Health Study and National Health and Nutrition Examination Survey) and 1 German (Prospective Cardiovascular Munster study) population samples. When the ATP III criteria were used, the prevalence of MS was higher in the United States than the German samples in both women (37% vs. 18%) and men (30% vs 25%), whereas when the IDF criteria were used, the prevalence of MS was 25% higher in the German than the American sample. Although in the United States both sets of criteria identified mostly the same people (concordance of about 90%), this was less true in Germany (concordance about 80%). To determine which criteria better predicted adverse cardiovascular outcomes, the incidence of coronary events associated with MS, as defined using the ATP III or the IDF criteria, were compared over a 10-year period among the middle-aged men in the German sample (n = 7,152). A total of 3.4% of men without MS developed an event. A much higher percentage of the men with MS defined by the ATP III criteria (10.7%) than the IDF criteria (5.5%) had a cardiovascular event. In conclusion, although the prevalence of MS was higher when the IDF criteria were used in the German sample, the IDF criteria have lower predictive power for coronary events.

Evidence for oxidative stress at elevated plasma thiol levels in chronic exposure to carbon disulfide (CS2) and coronary heart disease.

OBJECTIVES: Oxidative stress in plasma may be promoted by plasma thiols such as homocysteine. However, other thiols such as glutathione may also exert antioxidant effects in vitro and in vivo. To further investigate whether plasma thiols act as prooxidants or antioxidants, we compared plasma oxidative status in patients with coronary heart disease (CHD) and in subjects occupationally exposed to carbon disulfide (CS(2)). METHODS: Fifty-five subjects chronically exposed to CS(2), 53 CHD patients, and 52 healthy controls were examined. To assess plasma oxidative status, concentrations of thiobarbituric reactive substances (TBARS) and total antioxidative capacity (TAC), as well as ferritin and ceruloplasmin were determined. Antioxidative reserve was assessed by the determination of vitamine E, uric acid, superoxide dismutase, catalase, and glutathion peroxidase. In addition, protein and non-protein plasma thiol levels were measured. RESULTS: Patients in both groups had increased levels of plasma thiols as compared to controls: CS(2)-exposed subjects presented with increased levels of thiols associated with plasma proteins, whereas CHD patients presented with elevated total homocysteine and cysteine levels. TBARS were significantly increased and TAC was significantly decreased both in CS(2)-exposed subjects and in CHD patients. In addition decreased activity of glutathione peroxidase, an antioxidative enzyme inhibited by thiol-containing compounds, was noted in both groups. CONCLUSION: These results demonstrate that regardless of their metabolic origin increased thiols are associated with increased oxidative stress in plasma.

Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Münster (PROCAM) study.

BACKGROUND: The absolute risk of an acute coronary event depends on the totality of risk factors exhibited by an individual, the so-called global risk profile. Although several scoring schemes have been suggested to calculate this profile, many omit information on important variables such as family history of coronary heart disease or LDL cholesterol. METHODS AND RESULTS: Based on 325 acute coronary events occurring within 10 years of follow-up among 5389 men 35 to 65 years of age at recruitment into the Prospective Cardiovascular Münster (PROCAM) study, we developed a Cox proportional hazards model using the following 8 independent risk variables, ranked in order of importance: age, LDL cholesterol, smoking, HDL cholesterol, systolic blood pressure, family history of premature myocardial infarction, diabetes mellitus, and triglycerides. We then derived a simple point scoring system based on the beta-coefficients of this model. The accuracy of this point scoring scheme was comparable to coronary event prediction when the continuous variables themselves were used. The scoring system accurately predicted observed coronary events with an area under the receiver-operating characteristics curve of 82.4% compared with 82.9% for the Cox model with continuous variables. CONCLUSIONS: Our scoring system is a simple and accurate way of predicting global risk of myocardial infarction in clinical practice and will therefore allow more accurate targeting of preventive therapy.

The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women.

The recently discovered hormone leptin is primarily secreted by adipose tissue and serves as an internal signal indicating the size of body fat stores. The aim of the present study was to investigate the impact of the dietary fatty acid composition on serum leptin concentrations. Therefore, serum leptin levels were measured by RIA in healthy nonobese men (n = 30) and women (n = 25). First, all participants received a baseline high-fat diet, rich in saturated fat, for 2 wk and were then randomly assigned to one of three high-fat dietary treatments, which contained refined olive oil (rich in monounsaturated fatty acids, n = 19), rapeseed oil [rich in monounsaturated fatty acids and alpha-linolenic acid (18:3n-3), n = 17], or sunflower oil (rich in n-6-polyunsaturated fatty acids, n = 19) as the principal source of fat for 4 wk. On the rapeseed oil diet, serum leptin concentrations increased slightly in men [+0.25 ng/ml, T(9) = -2.778, P = 0.021], but decreased distinctly in women [-4.70 ng/ml, T(6) = 5.083, P = 0.002]. Both the olive oil and the sunflower oil diet did not affect serum leptin concentrations. Thus, it is proposed that serum leptin levels were affected by the high amount of alpha-linolenic acid in rapeseed oil. However, questions remain as to why this diet differently affected serum leptin in men and women.

Cardiovascular risk assessment in metabolic syndrome: view from PROCAM.

The near-epidemic proportions of diabetes mellitus and the metabolic syndrome over the past years are widely ascribed to a changing socioeconomic environment that contributes to excessive nutritional intake and sedentary lifestyle. Paradoxically, this gives room for expectations, because timely lifestyle and dietary intervention could decelerate the progression of diabetes, reduce the rate of development of cardiovascular complications, and reduce costs associated with treatment and rehabilitation. This approach,however, depends on the development of tools that allow precise estimation of risk of cardiovascular complications before the onset of diabetes mellitus and the risk of developing type 2 diabetes itself. This article reviews the progress that has been made toward reaching these goals based on the results of the PROspective Cardiovascular Münster (PROCAM) study.

Prediction of risk of coronary events in middle-aged men in the Prospective Cardiovascular Münster Study (PROCAM) using neural networks.

BACKGROUND: Logistic regression (LR) is commonly used to estimate risk of coronary heart disease. We investigated if neural networks improved on the risk estimate of LR by analysing data from the Prospective Cardiovascular Münster Study (PROCAM), a large prospective epidemiological study of risk factors for coronary heart disease among men and women at work in northern Germany. METHODS: We used a multi-layer perceptron (MLP) and probabilistic neural networks (PNN) to estimate the risk of myocardial infarction or acute coronary death (coronary events) during 10 years' follow-up among 5159 men aged 35-65 years at recruitment into PROCAM. In all, 325 coronary events occurred in this group. We assessed the performance of each procedure by measuring the area under the receiver-operating characteristics curve (AUROC). RESULTS: The AUROC of the MLP was greater than that of the PNN (0.897 versus 0.872), and both exceeded the AUROC for LR of 0.840. If 'high risk' is defined as an event risk >20% in 10 years, LR classified 8.4% of men as high risk, 36.7% of whom suffered an event in 10 years (45.8% of all events). The MLP classified 7.9% as high risk, 64.0% of whom suffered an event (74.5% of all events), while with the PNN, only 3.9% were at high risk, 58.6% of whom suffered an event (33.5% of all events). CONCLUSION: Intervention trials indicate that about one in three coronary events can be prevented by 5 years of lipid-lowering treatment. Our analysis suggests that use of the MLP to identify high-risk individuals as candidates for drug treatment would allow prevention of 25% of coronary events in middle-aged men, compared to 15% and 11% with LR and the PNN, respectively.

Non-LDL-related dyslipidaemia and coronary risk: a case-control study.

To assess the non-LDL-C-related dyslipidaemia risk of MI, 823 men aged 23 to 65 with a first MI were compared with 823 MI-free PROCAM controls matched for sex, age, smoking, DM, BP and LDL-C. Overall, the odds of MI in men with HDL-C < 1.15 mmol/L were 2.6 times those of men with HDL-C >or= 1.15 mmol/L, and the odds of MI in men with triglycerides >or= 1.71 mmol/L were 1.4 times those of men with lower triglycerides. If LDL-C was < 2.58 mmol/L, relative MI odds attributed to HDL-C < 1.15 mmol/L increased to 3.4, while relative odds attributed to triglycerides >or= 1.71 mmol/L increased to 2.6; men in this LDL category with HDL-C < 1.15 mmol/L and/or triglycerides >or= 1.71 mmol/L displayed an MI odds ratio of 5.0. MI risk associated with low HDL-C and/or high triglycerides is substantial, particularly if LDL-C is low.

Atherogenic dyslipidemia as evidenced by the lipid triad: prevalence and associated risk in statin-treated patients in ambulatory care.

OBJECTIVE: The prevalence of atherogenic dyslipidaemia (AD) can be assessed using the lipid triad (low high-density lipoprotein cholesterol [HDL-C] < 35 mg/dl, high triglyceride (TG) levels (≥ 200 mg/dl) and a high total cholesterol HDL-C ratio (TC/HDL-C>5). The aim of the present analysis was (1) to describe the prevalence of the lipid triad, (2) to quantify the associated cardiovascular risk on the basis of the PROCAM score, and (3) to calculate the additional risk reduction that can be obtained by adding nicotinic acid (NA) to a pre-existing statin therapy (model based on the outcomes of a previous randomized controlled study). METHODS: Descriptive post-hoc analysis of the German 4E registry in 24,500 patients receiving statins for primary cardiovascular prevention in ambulatory care. RESULTS: The sample comprised 24,500 patients in primary prevention, who had an overall 10-year risk of 16.2%. The prevalence of patients with lipid triad was 24.0%. The mean estimated risk reduction in the total sample (calculated on the basis of a mean LDL-C decrease by 24.3% and other lipid parameter changes) achieved after 6-week statin treatment was 46.6%, the estimated additional relative risk reduction by NA 45.1% (total effect compared to baseline about 70%). In the lipid triad group, the additional relative risk reduction by NA treatment was 42.9%. Relative treatment effects were consistent, irrespective of age and gender. Limitations of this analysis include the use of the TC/HDL-C ratio instead of the direct small dense LDL-C measurements, and the unknown variations of effect size of NA induced lipid reduction when used in combination with statins. CONCLUSIONS: Our model calculations indicate that the residual risk which persists after statin treatment could be substantially lowered if besides LDL-C also HDL-C and TG would be addressed, e.g. by adding NA to statin therapy. Definitive prospective studies are needed to confirm this hypothesis.

PROCAM Study: risk prediction for myocardial infarction using microfluidic high-density lipoprotein (HDL) subfractionation is independent of HDL cholesterol.

BACKGROUND: High-density lipoprotein (HDL) subfractions are among the new emerging risk factors for atherosclerosis. In particular, HDL 2b has been shown to be linked to cardiovascular risk. This study uses a novel microfluidics-based method to establish HDL 2b clinical utility using samples from the Prospective Cardiovascular Muenster (PROCAM) Study. METHODS: Method performance was established by measuring accuracy, precision, linearity and inter-site precision. Serum samples from 503 individuals collected in the context of the PROCAM study were analyzed by electrophoresis on a microfluidics system. Of these, 251 were male survivors of myocardial infarction (cases), while 252 individuals were matched healthy controls. HDL cholesterol, HDL 2b concentration and HDL 2b percentage were analyzed. RESULTS: This novel method showed satisfactory assay performance with an inter-site coefficient of variance of <10% for HDL 2b percentage. Parallel patient testing on 52 samples between two sites resulted in a correlation coefficient of r=0.95. Significant differences were observed in the HDL 2b subfraction between cases and controls independent of other risk factors. Including HDL 2b percentage in logistic regression reduced the number of false positives from 64 to 39 and the number of false negative cases from 48 to 45, in the context of this study. CONCLUSIONS: The novel method showed satisfactory assay performance in addition to drastically reduced analysis times and improved ease of use as compared to other methods. Clinical utility of HDL 2b was demonstrated supporting the findings of previous studies.

Genes, diet and public health.

Common chronic diseases such as coronary heart disease (CHD), diabetes, cancer, hypertension and obesity are significantly influenced by dietary and other behavioural habits. There is increasing scientific evidence that genetic factors (SNPs), conferring either protection or risk, also contribute importantly to the incidence of these diseases. SNPs are of particular interest because they influence disease in a complex but largely unknown manner by interacting with environmental and lifestyle factors. Because genetic factors also affect a person's response to dietary habits, SNPs likely will be useful in helping to determine and understand why individuals differ in their response to diets. Therefore, the discovery of SNPs will likely revolutionize not only the diagnosis of disease but also the practice of preventative medicine. Other developments, like new biomarkers and noninvasive imaging techniques, might turn out to be highly sensitive and specific in order to identify patients at risk, especially in cases with asymptomatic coronary heart disease. Thus, further knowledge of such new risk factors and their interaction with nutrition, has the potential to provide a more precise and personalized approach to prevent and treat chronic diseases like coronary artery disease, myocardial infarction and stroke.

Relationship between phytosterol levels and components of the metabolic syndrome in the PROCAM study.

BACKGROUND: Components of the metabolic syndrome such as hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol and obesity have been shown to be associated with increased cholesterol synthesis and reduced cholesterol absorption. In the present study, we measured the lathosterol/cholesterol ratio as an index of cholesterol synthesis and the ratios of cholestanol, campesterol and sitosterol to cholesterol as indices of cholesterol absorption, as well as components of the metabolic syndrome, in 324 men and 168 women from the PROCAM study, an epidemiological study in which raised sitosterol was previously associated with increased coronary risk. Our aim was to determine if the indices of cholesterol synthesis and absorption show a graded relationship with severity of metabolic syndrome. RESULTS: No differences were seen between men and women with regard to the relationship of either the lathosterol/cholesterol or the sitosterol/cholesterol ratios and severity of metabolic syndrome. On multiple regression analysis in men and women together, body mass index showed a positive relationship with the lathosterol/cholesterol ratio (r=0.257, P<0.001) and a negative relationship with the sitosterol/cholesterol ratio (r=-0.221, P<0.001). HDL-cholesterol showed a negative relationship with the lathosterol/cholesterol ratio (r=-0.166, P=0.001). Triglycerides showed a negative relationship with the sitosterol/cholesterol ratio (r=0.141, P=0.005). Overall, these relationships were graded across quintiles of HDL cholesterol, body mass index and triglyceride and across an index of metabolic syndrome severity (number of components present). Only the cholestanol/cholesterol ratio showed a graded relationship with estimated overall coronary risk. CONCLUSIONS: The metabolic syndrome is associated with increased cholesterol synthesis and reduced cholesterol absorption in a relationship that is graded across severity of the individual components of the syndrome and across an index of the severity of the metabolic syndrome as a whole.

Type 2 diabetes mellitus and risk of coronary heart disease: results of the 10-year follow-up of the PROCAM study.

BACKGROUND: American and European consensus opinions recommend that diabetes mellitus be regarded as a 'coronary risk equivalent', that is, as conferring the same risk of myocardial infarction as established coronary heart disease. We examined if this holds true for men in the Prospective Cardiovascular Münster Study (PROCAM). DESIGN: We conducted a single-centre, prospective, epidemiological study, calculating risk using the PROCAM calculator, which takes diabetes mellitus into account, in men at work in public authorities and large companies in the region of Münster, Germany. PARTICIPANTS: Five thousand, three hundred and eighty-nine men aged 35-65 years at recruitment participated, 3778 of whom were normoglycaemic, 1205 of whom displayed impaired fasting glycaemia, and 406 of whom suffered from diabetes mellitus. Coronary events (fatal or nonfatal myocardial infarction, sudden coronary death) occurring within 10 years of unbroken follow-up were assessed. RESULTS: Of men with diabetes mellitus 13.3% suffered a coronary event within 10 years, compared with 7.3% of men with impaired fasting glycaemia, and 5.3% of normoglycaemic men. Using the PROCAM risk calculator, only 26.5% of the men with diabetes mellitus were calculated to have a 10-year coronary event risk at or above the threshold of 20% (high risk) regarded as being equivalent to the risk conferred by established coronary heart disease. Eight percent of men with impaired fasting glycaemia and 5.5% of normoglycaemic men were at high risk. The positive predictive value of a high-risk estimate was 35% in men with diabetes, 32% in men with impaired fasting glycaemia, and 31% in normoglycaemic men. CONCLUSION: In PROCAM, less than a third of men with diabetes were classified as being at high risk of coronary events. It is therefore incorrect to regard the presence of diabetes mellitus as a coronary risk equivalent.

Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Münster (PROCAM) study.

BACKGROUND AND AIM: Sitosterolemia, a rare genetic disorder characterized by profoundly elevated plasma sitosterol concentrations, is associated with premature atherosclerosis in some individuals. This study was conducted to evaluate if the modest sitosterol elevations seen in the general population are also associated with the occurrence of coronary events. METHODS AND RESULTS: A nested case-control study using stored samples from male participants in the Prospective Cardiovascular Münster (PROCAM) study was performed. Each of 159 men who suffered a myocardial infarction or sudden coronary death (major coronary event) within 10 years of follow-up in PROCAM was matched with 2 controls (N = 318) by age, smoking status, and date of investigation. Analysis was performed using conditional logistic regression. Plasma sitosterol concentrations were elevated in cases compared with controls (4.94 +/- 3.44 micromol/L versus 4.27 +/- 2.38 micromol/L; P = 0.028). The upper quartile of sitosterol (>5.25 micromol/L) was associated with a 1.8-fold increase in risk (P < 0.05) compared with the lower three quartiles. Among men with an absolute coronary risk > or = 20% in 10 years as calculated using the PROCAM algorithm, high sitosterol concentrations were associated with an additional 3-fold increase in the incidence of coronary events (P = 0.032); a similar, significant relationship was observed between a high sitosterol/cholesterol ratio and coronary risk (P = 0.030). CONCLUSIONS: Elevations in sitosterol concentrations and the sitosterol/cholesterol ratio appear to be associated with an increased occurrence of major coronary events in men at high global risk of coronary heart disease. Further evaluations are warranted to confirm these preliminary findings.

Gap between guidelines and practice: attainment of treatment targets in patients with primary hypercholesterolemia starting statin therapy. Results of the 4E-Registry (Efficacy Calculation and Measurement of Cardiovascular and Cerebrovascular Events Including Physicians' Experience and Evaluation).

BACKGROUND: The aim of this study was to determine the achievement of National Cholesterol Education Program Adult Treatment Panel III goals in patients with primary hypercholesterolemia starting statin therapy in clinical practice. METHODS AND RESULTS: Data were collected by 4401 physicians in private practice on 52 848 patients aged 35-65 years (46.3% women, 53.7% men). 56.1% of patients had no manifested atherosclerosis (primary prevention) among whom 34.9% of men and 0.5% of women had a 10-year coronary heart disease risk over 20% (high-risk) as calculated using the Prospective Cardiovascular Münster study (PROCAM) algorithm. After 6 weeks of statins, only 6.9% of these high-risk men and 4.6% of these high-risk women reached their low-density lipoprotein (LDL) cholesterol target of 2.6 mmol/l or below (100 mg/dl). Even after 9 months, only 8.0% of these men and 6.2% of these women achieved their LDL target. No fewer than 57.3% of treated women had a coronary risk below 10%, and 18.8% of women were already at target before statins were prescribed. Of patients 43.9% had manifest atherosclerosis (secondary prevention). After 6 weeks of therapy, only 12.9% of the women and 16.3% of the men in this secondary prevention group reached LDL target levels of 2.6 mmol/l or below. Even after 9 months, only 21.3% of men and 17.3% of women with manifest atherosclerosis reached target LDL. CONCLUSIONS: Most high-risk patients do not achieve LDL targets. Overtreatment of low-risk groups is also very common.

Interferences in coagulation tests--evaluation of the 570-nm method on the Dade Behring BCS analyser.

The Dade Behring BCS is a coagulation analyser with optical reaction detection (standard 405 nm). The present study was conducted to evaluate measurement at 570 nm for analyses in interfering plasma samples. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer in normal (n=50), lipaemic (n=60), icteric (n=113), and haemolytic (n=58) samples were measured at 405 and 570 nm. As they are unaffected by the optical properties of the sample, the mechanical STAcompact analyser (Roche Diagnostics) and an ELISA technique were defined as the "comparison" methods. The percentage of valid PT results using the 570-nm method varied from 54% (lipaemic samples) to 97% (haemolytic samples). Valid aPTT measurements were found in 67% (lipaemic samples) up to 93% (icteric samples) of samples. Fibrinogen measurement revealed valid results in 58% (lipaemic samples) to 100% (haemolytic samples) of samples. The number of valid D-dimer results varied from 28% (lipaemic material) up to 100% (haemolytic material). Significant inter-method differences were found: aPTT in lipaemic (BCS 405 vs. 570 nm) and icteric samples (STAcompact vs. BCS 405 and 570 nm); fibrinogen in lipaemic (BCS 405 vs. 570 nm), icteric (BCS 405 vs. 570 nm; STAcompact vs. BCS 570 nm) and haemolytic samples (STAcompact vs. BCS 405 and 570 nm). Differences between the BCS 570-nm and the STAcompact methods were in most cases low and less pronounced than between the BCS 570- and 405-nm methods, making the BCS 570-nm method an alternative to measurement at 405 nm. Limitations have to be taken into account regarding lipaemic plasma.

Importance of arterial pulse pressure as a predictor of coronary heart disease risk in PROCAM.

AIMS: To investigate pulse pressure (PP) as an independent predictor of coronary heart disease (CHD) risk. METHODS AND RESULTS: On the basis of a 10-year follow-up of 5389 men aged 35-65 at recruitment into PROCAM, we used a proportional hazards model to calculate the effect of systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP on CHD risk after correcting for age, high-density lipoprotein cholesterol, LDL cholesterol, triglycerides, smoking, diabetes, and family history of premature CHD. Increases of 10 mmHg in DBP, SBP, and PP were associated with an increased CHD hazard ratio (HR) of approximately 10%. When the group was divided into the age groups <50, 50-59, and >59 years, this relationship was seen in the age group 50-59 years for DBP, SBP, and PP and in men aged > or =60 for PP only (25% increase in HR). Overall, CHD risk in men with PP > or =70 mmHg was more three times that of men with PP <50 mmHg. This increased risk was not apparent at age <50 years, was greatest at age >60 years, and was also present in men who were normotensive at recruitment (SBP < or =160 mmHg, DBP < or =95 mmHg). CONCLUSION: In older European men, increased PP is an important independent determinant of coronary risk, even among those initially considered normotensive.

The CAG repeat polymorphism in the androgen receptor gene is associated with HDL-cholesterol but not with coronary atherosclerosis or myocardial infarction.

BACKGROUND: Age-adjusted morbidity and mortality rates from coronary heart disease (CHD) are higher in men than in women. Androgens are suspected to be responsible for the male disadvantage. The genomic effect of androgens is mediated by the androgen receptor (AR), which has a polymorphic CAG repeat in exon 1. The number of repeats is inversely related to the transcriptional activity of the AR on target genes. METHODS: We investigated the association of this CAG repeat polymorphism with CHD and myocardial infarction (MI) in 2 independent case-control studies involving 544 Caucasian men. RESULTS: The number of CAG repeats in the AR gene correlated significantly with HDL-cholesterol (HDL-C) in controls (r = 0.21; P = 0.015). This effect was independent of triglycerides, body mass index, alcohol intake, smoking, and age in a multiple regression model (R(2) = 50%). Despite decreased HDL-C, lower CAG repeat numbers were not associated with increased risk for CHD (odds ratio = 0.82; 95% confidence interval, 0.50-1.36; P = 0.44) or MI in carriers of AR genes with lower CAG repeat numbers (odds ratio = 0.72; 95% confidence interval, 0.37-1.39; P = 0.33). CONCLUSIONS: Shorter, more androgenic AR alleles with fewer CAG repeats are associated with lower HDL-C, but not with an increased risk for CHD or MI, which argues against a detrimental androgen effect on cardiovascular risk under physiologic conditions.