Biomedical subjects
Publications and source records attributed to Jaap W Deckers.
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AIMS: Evidence is accumulating that inflammation plays a role in the pathophysiology of heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has pro-inflammatory properties. We investigated whether Lp-PLA2 activity is associated with heart failure. METHODS AND RESULTS: Lp-PLA2 activity was determined in a random sample of 1820 subjects from the Rotterdam Study, a population-based cohort study among persons aged 55 years and over. During a mean follow-up of 6.7 years, 94 heart failure cases occurred. We excluded participants with heart failure or coronary heart disease at baseline and we accounted for incident coronary heart disease during follow-up. We used Cox proportional hazard models to compute hazard ratios adjusted for age, sex, non-HDL cholesterol, HDL cholesterol, body mass index, systolic blood pressure, diastolic blood pressure, hypertension, diabetes mellitus, smoking, and C-reactive protein. The hazard ratio per unit increase of Lp-PLA2 activity was 1.03 [95% confidence interval (95% CI 1.01-1.05]; P for trend was 0.011. Hazard ratios for the second, third, and fourth quartiles were 1.06 (95% CI 0.55-2.04), 1.43 (95% CI 0.73-2.81), and 2.33 (95% CI 1.21-4.49), respectively, using the lowest quartile of Lp-PLA2 activity as the reference category. CONCLUSION: This study suggests that Lp-PLA2 activity is independently associated with incident heart failure.
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AIMS: Patients with stable coronary artery disease (CAD) are at increased risk. Estimation of individual risk is difficult. We developed a cardiovascular risk model based on the EUROPA study population and investigated whether benefit of long-term administration of the angiotensin-converting enzyme (ACE)-inhibitor perindopril was modified by risk level. METHODS AND RESULTS: A total of 12 218 patients with stable CAD were treated with 8 mg perindopril or placebo. Baseline patient characteristics were assessed for association with 1091 cardiovascular deaths or non-fatal myocardial infarction (MI). Risk factors were age over 65 years, male gender [hazard ratio (HR) 1.2], previous MI (HR 1.5), previous stroke and/or peripheral vascular disease (HR 1.7), diabetes, smoking, angina (all HR 1.5), and high serum cholesterol and systolic blood pressure. Treatment benefit by perindopril was consistent among high, intermediate, and low risk patients (HRs 0.88, 0.68, and 0.83, respectively). Risk reduction was thus not modified by absolute risk level. CONCLUSION: Risk factors such as age, male gender, smoking, total cholesterol, and blood pressure continue to play an important role once clinical sequellae of coronary heart disease have developed. Patients at moderate-to-high risk because of uncontrolled risk factors and those with other indications for ACE-inhibitors have the most to gain from ACE-inhibition.
AIMS: Contemporary data on the incidence of unrecognized myocardial infarction (MI) among subjects aged 55 and older are limited. METHODS AND RESULTS: We studied the incidence of recognized and unrecognized MI in the Rotterdam Study, a population-based cohort of men and women aged 55 and older. The baseline examination was performed during 1990-93, with follow-up examinations during 1994-95, and 1997-2000. Baseline and follow-up 12-lead ECGs were analysed by the Modular ECG Analysis System. The 5148 participants who had no evidence of prevalent infarction were the subjects for analysis. Incident recognized infarction was defined as the occurrence of a fatal or non-fatal event coded as I21 according to the International Classification of Diseases, 10th edition. A repeat ECG was available in 4187 subjects. An unrecognized infarction was considered to have occurred if there was electrocardiographic evidence in the absence of a clinically recognized event. During a median follow-up of 6.4 years, 141 incident recognized infarctions occurred and the incidence rate of this event was 5.0 per 1000 person years. The incidence was higher in men (8.4) than in women (3.1). The incidence rate of unrecognized infarction was 3.8 per 1000 person years. Men (4.2) and women (3.6) had approximately similar incidence. Hence, the proportion of unrecognized infarction was lower in men (33%) than in women (54%). This difference in proportion of unrecognized infarctions was independent of age. CONCLUSION: A high proportion of incident MIs remains clinically unrecognized. As a history of MI is associated with an increased risk of repeat cardiovascular complications, our data suggest a need for periodical electrocardiographic screening to recognize (prevalent) infarctions and to install effective preventive treatment in those aged 55 and older.
OBJECTIVES: This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. BACKGROUND: In developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death. METHODS: This study was conducted as part of the Rotterdam Study, a prospective population-based cohort study that comprises 3,105 men and 4,878 women aged 55 years and older. The QTc interval on the electrocardiogram was determined during the baseline visit (1990 to 1993) and the first follow-up examination (1993 to 1995). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis. RESULTS: During an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men, >470 ms in women) was associated with a three-fold increased risk of sudden cardiac death (hazard ratio, 2.5; 95% confidence interval, 1.3 to 4.7), after adjustment for age, gender, body mass index, hypertension, cholesterol/high-density lipoprotein ratio, diabetes mellitus, myocardial infarction, heart failure, and heart rate. In patients with an age below the median of 68 years, the corresponding relative risk was 8.0 (95% confidence interval 2.1 to 31.3). CONCLUSIONS: Abnormal QTc prolongation on the electrocardiogram should be viewed as an independent risk factor for sudden cardiac death.
BACKGROUND: Experimental studies have shown that the known biologic effects of proinflammatory cytokines could explain many aspects of the syndrome of heart failure. The inflammatory marker that presently seems most suitable to assess inflammation is C-reactive protein (CRP). This study was designed to investigate the association between serum CRP levels, as determined by high-sensitivity assay, and the occurrence of heart failure. METHODS: Serum CRP levels were available from 6437 men and women without heart failure, aged > or = 55 years, from the prospective population-based Rotterdam Study. Cox proportional hazards analysis was used to determine risk of heart failure for sex-specific quartiles of CRP. RESULTS: C-reactive protein levels in the highest versus the lowest quartile showed increased hazard ratios of incident heart failure. The age- and sex-adjusted hazard ratio was 2.64 (95% CI 2.04-3.43) for all participants. For men, the age adjusted hazard ratio was 4.37 (2.87-6.66), and for women, 1.86 (1.32-2.62). The interaction term of CRP with sex was highly significant. After additional adjustment for established cardiovascular risk factors, the association attenuated slightly in men and substantially in women, becoming 3.73 (2.40-5.78) and 1.42 (0.99-2.03), respectively. Excluding participants with prevalent coronary heart disease and accounting for incident coronary heart disease resulted in a further attenuation of the hazard ratios, which was proportionately larger in men than in women. CONCLUSIONS: C-reactive protein is strongly and independently associated with occurrence of heart failure in men. In women, the association is weaker and does not persist after accounting for established cardiovascular risk factors.
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AIMS: Treatment guidelines for patients with established coronary disease emphasize the importance of smoking cessation. We aimed to study smoking behaviour in European patients, as well as trends in this behaviour over time. We further aimed to evaluate the relation between selected patient characteristics and smoking cessation. METHODS AND RESULTS: We studied patients who were enrolled in the second European Action on Secondary Prevention through Intervention to Reduce Events (EUROASPIRE) survey, which was undertaken in 15 European countries during 1999-2000. Consecutive patients, < or =70 years were identified after coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, admission for myocardial infarction, or admission for myocardial ischaemia. Patients were then interviewed, at a median of 1.5 years after the index event. During the interview, data were collected on a broad range of clinical characteristics, including smoking status, which was validated by breath carbon monoxide levels. The prevalence of smoking was compared with data from the first EUROASPIRE survey, which had a similar design, and was conducted during 1995-96. In EUROASPIRE II, 5551 patients attended the interview and 1172 (21%) were (persistent) smokers. No decrease in smoking prevalence was observed similar to the first survey (19%). The proportion of smokers was 39% in patients aged <50, 26% in patients aged 50-60, and 14% in patients aged > or =60. Men and women had similar prevalence. A verbal advice to give up smoking by a medical professional was given to 99% of the 2244 pre-event smokers, and 48% actually stopped. This proportion was relatively high in elderly patients > or =60 years (53%), patients with a university level of education (56%), and patients with a myocardial infarction as the index event (52%). The proportion of stopped smokers was low in patients <50 years (41%) and in patients with myocardial ischaemia as the index event (38%). CONCLUSION: The prevalence of smoking in European patients with established coronary disease is too high: one out of each five patients smokes, despite a personal advice to stop. Thus, still there is a need for the development of effective smoking cessation programmes.
OBJECTIVE: We examined the independent prognostic value of the four subscales of the Heart Patients Psychological Questionnaire (HPPQ) on mortality in acute myocardial infarction (AMI) survivors up to 8 years after the event. METHODS: The HPPQ, which measures well-being, feelings of being disabled, despondency and social inhibition, was administered to 567 AMI patients during hospitalisation and at 3 months follow-up. The patients were followed for 8 years. RESULTS: During follow-up, 157 patients (28%) died. Forty-one percent of the patients had a score indicating at least mild to moderate feelings of being disabled. Patients with feelings of being disabled were at increased risk of mortality compared with those having a low score, adjusted for other cardiac risk factors [hazard ratio (HR)=1.8, 95% confidence interval (CI)=1.3-2.5]. There was no interaction between feelings of being disabled and gender. None of the other HPPQ subscales were related to mortality or recurrent myocardial infarction (MI). When the study population was stratified by low and high clinical risk (43% vs. 57%, respectively), feelings of being disabled was the most prominent predictor of mortality in the low-risk group (HR=3.5, 95% CI=1.4-8.8). CONCLUSION: Feelings of being disabled measured at baseline and at 3 months was the most prominent predictor of mortality in low-risk patients 8 years post-MI. This finding adds to the existing knowledge that psychosocial variables influence morbidity and mortality in cardiac patients.
BACKGROUND: The response to angiotensin-I converting enzyme (ACE)-inhibitor therapy is highly variable. Residual ACE activity during treatment, potentially modified by the ACE insertion/deletion (I/D) polymorphism, may explain part of this variability. We studied the possible interaction between ACE-inhibitor therapy in patients with hypertension and the ACE I/D polymorphism in incident heart failure and death. METHODS: We studied 3365 hypertensive participants of the population-based Rotterdam Study, without heart failure at baseline for whom ACE-genotyping was successful. Incident heart failure was defined according to established criteria. In addition, total and cardiovascular mortality were studied as endpoints. A Cox regression model with use of ACE-inhibitors defined as time-dependent covariates was used for data-analysis. Interaction was tested in this model assuming an allele-effect relationship. RESULTS: Although we could not demonstrate a beneficial effect of ACE-inhibitors, there was significant interaction between the ACE I/D polymorphism (II-ID-DD) and ACE-inhibitor use in the prediction of total and cardiovascular mortality. Mortality risk associated with treatment increased with the number of D alleles present; e.g. for total mortality in the II genotype group: RR=0.95 (95% CI 0.63-1.45), in the ID genotype group: RR=1.08 (95% CI 0.84-1.38) and in the DD genotype group: RR=1.61 (95% CI 1.18-2.18). No statistically significant interaction was found for incident heart failure. CONCLUSION: The results of our study suggest a relative resistance to ACE-inhibitor therapy in subjects with hypertension and the DD genotype compared to the II genotype, with the ID genotype in an intermediate position.
We studied 4,963 participants of the population-based Rotterdam Study and found that a genetically determined chronic exposure to low insulin-like growth factor-I (IGF-I) levels is associated with an increased risk for heart failure in elderly patients.
PURPOSE: The Rose questionnaire is a standardized method of measuring angina pectoris in general populations. Electron-beam computed tomography (CT) is a non-invasive technique to quantify the amount of coronary calcification. In a population-based study, we investigated the association between Rose questionnaire angina pectoris and coronary calcification. METHODS: The Rotterdam Coronary Calcification Study is embedded in the Rotterdam Study, a population-based study in subjects aged > or = 55 years. Participants of the Rotterdam Coronary Calcification Study underwent an electron-beam CT scan between 1997 and 2000. Coronary calcification was quantified in a calcium score according to Agatston's method. Rose questionnaire angina pectoris was assessed during a home interview. The first 2013 participants were included in the present analyses. RESULTS: In men, the presence of Rose questionnaire angina pectoris was associated with a 12.9-fold (95% confidence interval: 3.8-43.7) increased risk of a calcium score >1000 (reference: calcium score 0-100). The corresponding relative risk in women was 4.8 (2.0-11.3). Similar results were found when we computed sex-specific quartiles of the calcium score. CONCLUSIONS: Rose questionnaire angina pectoris is strongly associated with the amount of coronary calcification. Rose questionnaire angina pectoris corresponds better with the amount of coronary calcification in men than in women.