European Journal of Preventive Cardiology

Background Chronic Helicobacter pylori infection has been implicated as a risk factor for stroke and other cardiovascular disease. It has been suggested that it acts by promoting atherogenesis. A particular strain of H. pylori, the cytotoxin gene A strain (CagA strain), which has been associated with increased inflammation, has been reported to account for much of this relationship. An early estimate of atherosclerosis can be obtained by ultrasonic imaging of the carotid artery to determine intima-media thickness (IMT). We determined whether H. pylori infection, and particularly the CagA strain, is associated with increased IMT.

Methods In 983 normal population individuals we measured common carotid artery (CCA) IMT. From serum samples we determined H. pylori and CagA status.

Results There was no significant association between H. pylori seropositivity and CCA IMT after controlling for age and gender. There were significant relationships between H. pylori seropositivity and a number of conventional cardiovascular risk factors (age, systolic and diastolic blood pressure, body mass index, smoking) and after controlling for these the magnitude of the regression coefficient was reduced by a further half. Amongst H. pylori seropositives the CagA strain was associated with increased IMT after controlling for age and gender (B=0.0256, 95% CI 0.001–0.050, P=0.038). The relationship was no longer significant after controlling for other cardiovascular risk factors. (B=0.0194, 95% CI −0.004–0.042, P=0.098).

Conclusions H. pylori and the CagA strain are not major risk factors for early arteriosclerosis as assessed by carotid artery intima-media thickness.

The ATHEROMA study is a prospective, multicentre, randomized controlled study in Japan to assess the changes of coronary atherosclerosis of patients with pre-existing coronary artery disease (CAD) by cholesterol-lowering therapy (CLT) using pravastatin 10–20mg per day for 3 years. The primary objective is to evaluate the changes in coronary minimum lumen diameters by quantitative coronary arteriography, and the secondary outcome is to observe morphological changes of plaques and clinical events including mortality, recurrence of CAD and the requirement of any coronary intervention. The primary objective will test the hypothesis that CLT results in a beneficial effect on coronary vessels in patients with coronary atherosclerosis in Japan, where the incidence of CAD is the lowest among industrialized countries. A total of 373 eligible patients were recruited from 799 patients and allocated to a dietary (n=187) and pravastatin regimen (n=186) by the minimization method. Clinical characteristics in the two groups were well matched and there were no differences in serum lipids and coronary status between them. The average ± SD (range) of total, LDL and HDL cholesterol were 225.6 ± 17.3 mg/dl, 141.9 ± 21.2 mg/dl and 49.4 ± 12.0 mg/dl, respectively. Three years of follow-up were completed in late 2000, and cine angiograms blinded through the study coordinating centre were interpreted at the angiographic core laboratory. The final results, which are due to be published in 2002, will reveal whether or not specifically designed prophylactic strategy based on different cultural background is required.

Background Coronary heart disease (CHD) is the leading cause of death in Malaysia, despite its status as a developing country. The rural population is thought to be at low risk.

Objective To investigate the prevalence of risk factors and global risk profile among rural Malays in Malaysia.

Methods We studied 609 rural Malay subjects (346 females, 263 males; age range 30–65 years). Blood pressure (BP), body mass index (BMI), waist–hip ratio (WHR), smoking habits and family history of premature CHD were documented. Fasting blood samples were analysed for serum lipids, lipoprotein (a), plasma glucose and fibrinogen. Oral glucose tolerance tests were performed using 75 g anhydrous glucose.

Results The prevalence of hypercholesterolemia for total cholesterol concentrations of ≥ 5.2, ≥6.5 and ≥7.8 mmol/l were 67.3, 30.5 and 11.8% respectively. There was a high prevalence of low serum high-density lipoprotein cholesterol (13.1%), hypertension (30.3%), smokers (24.4%), diabetes (6.4%), impaired fasting glucose or glucose tolerance (13.9%), overweight or obesity (44.7%) and increased WHR (48.5%). Global risk assessment showed that 67.3% of the study population were at risk, with 15.9, 18.9 and 32.5% in the mild, moderate and high risk categories respectively.

Conclusion Prevalence of risk factors was high in the rural population. Global risk assessment showed a high-risk profile with two-thirds being at risk, and one-third being categorized into the high-risk group. Although rural communities were considered at low risk of developing CHD, this is changing fast, possibly due to the rapid socio-economic development, in addition to underlying genetic predisposition.

Background While genetic variation accounts for a large proportion of interindividual differences in coronary artery disease (CAD) development, environmental factors such as cigarette smoking may genotype-dependently initiate or accelerate the risk. Glutathione S-transferase mu1 (GSTM1) is one of the GST isoenzymes and contributes to the detoxification process of organic compounds produced by cigarette smoking. In the present study we explored the hypothesis that GSTM1 deficiency, caused by GSTM1 null allele, may predispose subjects to cigarette smoking related CAD risk.

Design Cross-sectional.

Methods We genotyped the GSTM1 null allele in 868 angiographically characterized CAD patients who were consecutively recruited in the present study.

Results The frequency of the null genotype in this high-risk patient population was 57.1% (55.4% for males and 61.0% for females). While 75.7% male and 50.7% female null GSTM1 patients had significant CAD as defined by one or more significantly stenosed coronary arteries, 79.3% male and 48.3% female patients with positive GSTM1 also had the significant CAD (P > 0.05). However, although 54.3% male and 55.2% female GSTM1 null patients had triple vessel disease, only 45.7% male and 44.5% female GSTM1 positive patients had the severe disease. Controlling for cigarette smoking did not change the relationship. The occurrences of MI were 37.9% in male and 31.4% in female with the null genotype whereas they were 42.8% in male 37.6% in female with positive GSTM1 (P > 0.05). Using logistic regression analyses, we found no interactions between GSTM1 genotype and cigarette smoking in relation to CAD or MI.

Conclusions While our data may be consistent with that the GSTM1 null genotype predisposes subjects to cigarette smoking related severe CAD, interactive effect on CAD risk is minor and insignificant. GSTM1 deficiency alone is not sufficient to cause CAD.

Background Statin–fibrate combinations are very effective in the treatment of familial combined hyperlipidaemia (FCHL). Nonetheless, they have not been extensively used because of the fear of side effects. Thus, a therapeutic alternative is required for this lipid disorder.

Objective To compare the long-term (one-year) efficacy of atorvastatin monotherapy with those of four statin–fibrate combinations in 675 FCHL patients.

Methods Patients were randomly assigned to atorvastatin monotherapy (A 20 mg/day) n=134, or pravastatin (P 20 mg/day)+gemfibrozil (G 1200 mg/day) n=135, simvastatin (S 20 mg/day)+G (1200 mg/day) n=137, P (20 mg/day)+ciciprofibrate (C 100 mg/day) n=135, and S (20 mg/day)+C (100 mg/day) n=134.

Results Twelve patients on statin–fibrate combinations were withdrawn from the study because of side effects: Three because of CK elevation, two because of myalgia and seven due to increase in serum transaminase levels. One patient on A was withdrawn because of persistent epigastric discomfort. Atorvastatin reduced low density lipoprotein cholesterol and apoprotein B more than all four combinations (−45% vs. maximum −40% of S+C, and −39% vs. maximum −32% of the same combination, respectively, P < 0.001 for both), but had a lesser effect on triglycerides (−38% vs. maximum −53% of S+C, P=0.0002) and high density lipoprotein cholesterol (6% vs. maximum 21% of S+G, P=0.0003). The effect of A on plasma fibrinogen was analogous to that of G combinations (−8% vs. −9% of P+G and −11% of S+G, P=NS vs. baseline and among each other) and inferior to that of the ciprofibrate combinations (−8% vs. −24% of P+C, P=0.0002 and −26% S+C, P=0.0001). A had a lower treatment cost and better patient compliance, P=0.04 vs. C combinations and P=0.02 vs. G combinations.

Conclusions The data suggest that statin–fibrate combinations have a beneficial effect on all lipid parameters. Atorvastatin monotherapy has a better effect on LDL-C and apoprotein B than statin–fibrate combinations, but a lesser effect on HDL-C, TG and in the case of ciprofibrate combinations, fibrinogen. The clinical significance of these findings should be tested in a large, long-term survival study.

The present study uses early diagnosis of ischaemic coronary heart disease (ICHD) as a proxy for disease malignancy in testing the statistical strength of association, and uniqueness/confounding, of several psychometric scales that have previously been found to prospectively predict death in cardiac samples (Beck Depression Inventory, Crown–Crisp Phobic Anxiety Scale, Type D Scale & Ketterer Stress Symptom Frequency Checklist). Eighty-three patients (no. of females=35) with documented ICHD were assessed for traditional and psychometric risk factors. The psychometric risk factors were moderately to strongly intercorrelated, and strongly confounded in their relationship to age at initial diagnosis. In a stepwise multiple regression, only the AIAI (aggravation, irritation, anger and impatience) scale of the Ketterer Stress Symptom Frequency Checklist (KSSFC) survived as a predictor of age at initial diagnosis (P=0.016). In a subgroup of the sample for whom the Spouse/Friend Version of the KSSFC was received (n=58, or 70%), spouse/friend reported AIAI survived as the only predictor (P=0.010). While present results need replication in a prospective study of diagnosed ICHD patients for all important clinical outcomes, only one psychometric screening instrument may be necessary to identify patients in need of treatment.

Background The present study was carried out to investigate risk factors for developing coronary artery disease in wives of patients with acute myocardial infarction.

Subjects and methods Risk factors for developing coronary artery disease were investigated in 50 wives of patients who developed an acute myocardial infarction (group A) and were compared with those of 50 wives of normal healthy men (group B). The average age was 50.20 ± 1.56 years (mean ± SD) and 50.20 ± 1.53 years for group A and group B respectively. The parameters assessed were: Plasma cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), systolic and diastolic blood pressure, smoking habits and body mass index (BMI).

Results The levels of LDL-C in the wives of patients with myocardial infarction were higher than those of the wives of normal healthy men (167.8 ± 5.84 mg/dl and 148.4 ± 4.85 mg/dl, respectively, P < 0.01). Moreover, HDL-C concentrations were lower in the wives of the patients (51.34 ± 0.92 mg/dl) than in the wives of the healthy men (58.14 ± 1.39 mg/dl), (P < 0.001). Finally, TG levels were higher in the wives of the patients (132.2 ± 7.9 mg/dl) than in the wives of the normal healthy men (96.9 ± 5.94 mg/dl) (P < 0.01).

Conclusions Although plasma lipid levels themselves were not excessively high, the wives of patients with an acute myocardial infarction are at a higher risk of developing coronary artery disease than the wives of normal healthy men, in the long term, due to higher levels of LDL-C and TG as well as lower levels of HDL-C.

Objectives To investigate whether endothelial-dependent vasodilation is altered in healthy subjects with a family history of myocardial infarction.

Setting Tertiary University Hospital

Subjects and design Fifty apparently healthy subjects selected from the general population were subjected to an evaluation of endothelial-dependent vasodilation (EDV) and endothelial-independent vasodilation (EIDV) by means of local infusion of methacholine (MCh, 2 and 4 μg/min) and sodium nitroprusside (SNP, 5 and 10 μg/min) with measurements of forearm blood flow with venous occlusion plethysmography. The occurrence of plaque and the intima-media thickness of the carotid arteries were determined by ultrasonography.

Results Subjects reporting at least one parent suffering from myocardial infarction (n=11) showed a significantly lower EDV than subjects without such a family history (21 ± 3.7 vs. 26 ± 6.7 ml/min/100 ml tissue at MCh 4 μg/min, P<0.05). EIDV was not significantly different between the groups (21 ± 6.8 vs. 18 ± 5.4 ml/min/100 ml tissue at SNP 10 μg/min). Age, sex distribution, body mass index, waist to hip ratio, blood pressure, lipids, fasting blood glucose, smoking habits and status of the carotid arteries were not significantly different between the groups.

Conclusion A family history of myocardial infarction was found to be associated with an impaired endothelial-dependent vasodilation in the forearm of apparently healthy subjects. The risk factor profile was not different from the control group, suggesting that genetic factors are responsible for the impaired endothelial-dependent vasodilation.

Background Recently, we localized the Human Poliovirus Receptor Related 2 Gene (PRR2) 17kb centromeric to the gene for apolipoprotein E (APOE). Common polymorphisms in the latter have been found, in some studies, to be related to coronary heart disease (CHD) but the PRR2 gene has not been studied in this context. Here, we examined relationships between a PRR2 Sau96I (A/G) polymorphism, the ∊2, 3 and 4 alleles of APOE and CHD.

Design and methods Consecutive Caucasian patients (n=640) < 50 years with angiographically documented coronary obstructive disease and/or with unequivocal myocardial infarction were compared with 624 control subjects, aged 30–50 years, randomly selected from the community and without a history of CHD.

Results An excess of PRR2-A homozygotes was observed in cases (20% vs. 15%; OR 1.4, CI 1.04–1.86, P=0.026) particularly in those with single vessel disease (OR 1.7, CI 1.2–2.4, P<0.01).

The A allele was in linkage disequilibrium with the ∊4 allele and the G allele with the ∊2. Overrepresentation of the A allele and underrepresentation of the G allele in the CHD group did not reach significance (P=0.054). While the ∊2 allele was under-represented in the CHD group (OR 0.64, CI 0.46–0.89, P=0.009), the ∊4 allele was not significantly overrepresented.

Conclusion The relationship between the PRR2 Sau96I (A/G) polymorphism and early onset coronary artery disease may be due to linkage disequilibrium with the APOE gene and underrepresentation, or a protective effect, of the ∊2 allele. Alternatively, since A allele homozygosity is particularly overrepresented, the relationship could be more direct, perhaps through a viral association.