Genotype combinations of plasminogen activator inhibitor-1 and angiotensin-converting enzyme genes and risk for early onset of coronary heart disease.

BACKGROUND: Both angiotensin-converting enzyme genotype and plasminogen activator inhibitor type 1 genotype have an effect on fibrinolytic components and hence, may increase risk or advance occurrence of coronary heart disease. We examined the association of the angiotensin-converting enzyme and the plasminogen activator inhibitor type 1 genotypes, and their combinations, with early onset of coronary heart disease in a cohort of 907 patients with coronary heart disease. DESIGN AND METHODS: All patients with a coronary heart disease (International Classification of Diseases, 9th Rev. pos. 410-414), aged 30-70 years and participating in an inpatient rehabilitation program between January 1999 and May 2000 in two clinical centres in Germany were enrolled. The plasminogen activator inhibitor type 1 and the angiotensin-converting enzyme genotypes were determined by polymerase chain reaction, and the distribution was compared between patients with early (< or =55 years) and late (>55 years) onset of coronary heart disease. A multivariate analysis was employed to adjust for potentially confounding factors. RESULTS: Of the 907 included patients, 408 (45.0%) developed coronary heart disease before the age of 55 years. For the 4G/4G genotype of plasminogen activator inhibitor type 1 the odds ratio for early onset of coronary heart disease was 1.68 [95% confidence interval (CI) 1.01-2.57] and for the D/D genotype of angiotensin-converting enzyme the odds ratio was 1.22 (95% CI 0.84-1.76) after adjustment for covariates. In multivariate analysis an odds ratio of 3.10 (95% CI 1.51-6.36) was found for the association between the combined homozygosity for both polymorphisms (plasminogen activator inhibitor type 1 genotype 4G/4G and angiotensin-converting enzyme genotype D/D) and onset of coronary heart disease before the age of 55 years after controlling for sex, age, smoking, diabetes, hypertension, hyperlipidemia and school education. CONCLUSION: The co-existence of the 4G/5G polymorphism of the plasminogen activator inhibitor type 1 gene and the I/D polymorphism of the angiotensin-converting enzyme gene increases the risk for early onset of coronary heart disease in this population.

The diagnosis of a smoking-related disease is a prominent trigger for smoking cessation in a retrospective cohort study.

OBJECTIVE: We evaluated the impact of demographic factors, smoking patterns, and the occurrence of smoking-related diseases on smoking cessation, with a particular emphasis on the temporal relationship between diagnosis of smoking-related diseases and cessation. STUDY DESIGN AND SETTING: A cohort was assembled of participants of a general health screening examination aged 50-74 years. Lifetime smoking habits and medical history were obtained by a self-administered questionnaire. In a retrospective cohort study approach, predictors of cessation among ever-smokers (n = 4,575) were identified using the extended proportional hazards model. RESULTS: Male gender, late onset of smoking, and higher educational level were predictive of cessation. However, the by far strongest predictors of cessation were diagnoses of smoking-related diseases: relative cessation rates in the year of disease occurrence were 11.2 for myocardial infarction (95% confidence interval CI = 8.9-14.0), 7.2 for stroke (95% CI = 5.1-11.6), 2.5 for diabetes mellitus (95% CI = 1.6-4.0) and 4.8 for cancer (95% CI = 3.1-7.4) relative to years before diagnosis of the respective diseases. CONCLUSION: Our results underline the key role of perceived detrimental effects of smoking for cessation. When smokers personally experience the health consequences of smoking, many permanently quit.

The impact of body weight on smoking cessation in German adults.

OBJECTIVE: To assess the relevance of pre-existing body weight for successful smoking cessation among women and men. METHODS: We carried out a retrospective cohort analysis among 4270 ever smoking participants of a general health screening examination in Germany recruited from July 2000 to June 2002 aged 50 to 74, who provided lifetime histories of both body weight and smoking. RESULTS: In the extended Cox model, the relative cessation rate (RCR) increased significantly with increasing body mass index (BMI) among both genders (test for trend: P < 0.01 for women and P < 0.0001 for men). In women, this effect was mainly due to a lower cessation rate in low-weight (BMI <20) smokers (adjusted RCR = 0.76, 95% confidence interval (CI) 0.62-0.95), whereas in men, the effect was mainly due to a higher cessation rate among overweight and obese smokers (adjusted RCR = 1.26, 95% CI 1.11-1.35, and 1.38, 95% CI 1.17-1.63, respectively) compared to normal-weight smokers. CONCLUSIONS: While in men, overweight and obesity are associated with increased smoking cessation, possibly related to increased health concerns, in women, low weight is associated with decreased smoking cessation, possibly related to increased fear of weight gain.

Smoking, apolipoprotein E genotype, and early onset of coronary heart disease.

BACKGROUND: We examined the association between smoking, apolipoprotein E (ApoE) genotype, and early onset of coronary heart disease (CHD). DESIGN AND METHODS: Smoking behaviour and ApoE genotype of 904 patients with CHD aged 30-70 years were assessed with respect to age at onset of CHD. RESULTS: The adjusted odds ratio for early onset of CHD (< or =55 years) was 1.86 (95% confidence interval, 1.31-2.62) for smokers compared to non-smokers. The ApoE genotype had no significant influence and there was no significant interaction between ApoE genotype and smoking. CONCLUSION: We found smoking but not ApoE genotype to be an independent risk factor for early onset of CHD.

Genotype and plasma concentration of cystatin C in patients with coronary heart disease and risk for secondary cardiovascular events.

OBJECTIVE: Cysteine proteases and their inhibitors such as cystatin C are assumed to play an important role in the pathogenesis of atherosclerosis and coronary heart disease (CHD). The aim of the study was to investigate the impact of cystatin C polymorphisms on cystatin C plasma levels and on prognosis of patients with CHD. METHODS AND RESULTS: Four polymorphisms in the promoter and exon 1 of the cystatin C gene (-82GC, -5GA, +4AC, and +148AG) and cystatin C plasma levels were determined in a cohort of 1013 patients with manifest CHD and aged 30 to 70 years participating in an in-hospital rehabilitation program. Patients were followed-up for a mean of 33.5 months and a combined end point (fatal and nonfatal cardiovascular disease [CVD] events) was used as the outcome variable. The major haplotype -82G/-5G/+4A was associated with cystatin C plasma levels with persons homozygous for the major haplotype having the highest levels (P=0.01). However, the haplotype was not associated with fatal and nonfatal cardiovascular events during the 3-year follow-up. CONCLUSIONS: The major haplotype -82G/-5G/+4A of the cystatin C gene determines plasma levels of cystatin C with homozygous persons having the highest plasma levels, but there was no association with secondary CVD events in this study.

Drug interactions in primary care: impact of a new algorithm on risk determination.

BACKGROUND: If managed adequately, many drug interactions do not result in clinical manifestations. Earlier studies may have overestimated the risk arising from drug interactions because they usually reported interaction frequencies and the severity of potential outcomes irrespective of their manageability. OBJECTIVE: Our objective was to estimate the risk associated with drug interactions in a large population when not only the severity of possible clinical events but also measures of their prevention (manageability, modulating factors) are considered. METHODS: We evaluated all drug pairs concurrently prescribed to 9481 adults aged 50 to 75 years who participated in a health-screening examination. Drug interactions were evaluated by use of an algorithm with 4 decision layers (severity, manageability, risk/benefit assessment, and patient-related risk factors), and this risk evaluation was compared with the conventional evaluation solely on the basis of severity. RESULTS: More than 52% of the patients received combination therapy. Interaction information was available in a standard source (DRUGDEX; Thomson MICROMEDEX, Greenwood Village, Colo) for only 1029 of all 13,672 individual prescribed drug pairs. Of the drug pairs, 881 (6.4%) were identified as interacting. Of these 881 interactions, 132 (15.0%) were of major severity but 101 of 132 (76.5%) were considered manageable. Only 31 (23.5%) of 132 major interactions (ie, 31/881 [3.5% of all interacting pairs]) offered no management options and should thus be avoided. CONCLUSION: For many commonly prescribed drug pairs, explicit drug interaction information is currently not available in DRUGDEX. For major interactions with published evidence, the overwhelming majority were manageable, and therefore risk estimates only based on the severity of potential outcomes will grossly overestimate the risk associated with such combinations.

Relation among alcohol dehydrogenase 2 polymorphism, alcohol consumption, and levels of gamma-glutamyltransferase.

In human beings, alcohol is metabolized primarily by alcohol dehydrogenase 2 (ADH2) and acetaldehyde dehydrogenase 2 (ALDH2). Whereas polymorphisms of the ALDH2 are common in Asian persons, polymorphisms of the ADH2 seem to be more important in Caucasian individuals. The aim of this study was to assess the relation among ADH2 polymorphism, alcohol consumption, and levels of gamma-glutamyltransferase (GGT). The question was examined among 1,663 subjects (736 men and 927 women) participating in a national representative health and nutrition survey (VERA substudy of the German National Nutrition Survey). Alcohol consumption was assessed through responses to a semiquantitative food frequency questionnaire (FFQ), and the ADH2 restriction fragment length polymorphism (RFLP) Mae III and GGT levels were analyzed from frozen serum samples. The relations between the polymorphism and alcohol consumption and between alcohol consumption and GGT levels according to the polymorphism were assessed with the use of descriptive statistics and contingency table analysis. Of the subjects studied, 2.8% were homozygous or heterozygous for the ADH2*2 allele, and high levels of alcohol consumption (>20 g/day) were less common among these subjects (8.5%) than among subjects with the ADH2*1 allele (19.9%). Median levels of GGT increased with increasing levels of alcohol consumption. This increase tended to be stronger among subjects with the ADH2*2 allele than among other subjects, although differences were not statistically significant (P value for interaction=.1) given the small number of subjects with the polymorphism. These results are consistent with the hypothesis that subjects with the ADH2*2 allele, on the one hand, might tend to drink less alcohol but, on the other hand, might be at increased risk of alcohol-related effects on the liver with consumption of larger amounts of alcohol. However, this hypothesis needs to be evaluated among larger population samples.