Ambient air pollution and daily mortality among survivors of myocardial infarction.

BACKGROUND: Certain subgroups in the general population, such as persons with existing cardiovascular or respiratory disease, may be more likely to experience adverse health effects from air pollution. METHODS: In this European multicenter study, 25,006 myocardial infarction (MI) survivors in 5 cities were recruited from 1992 to 2002 via registers, and daily mortality was followed for 6 to 12 years in relation to ambient particulate and gaseous air pollution exposure. Daily air pollution levels were obtained from central monitor sites, and particle number concentrations were measured in 2001 and estimated retrospectively based on measured pollutants and meteorology. City-specific effect estimates from time-series analyses with Poisson regression were pooled over all 5 cities. RESULTS: Particle number concentrations and PM10 averaged over 2 days (lag 0-1) were associated with increased total nontrauma mortality for patients of age 35 to 74 (5.6% [95% confidence interval, 2.8%-8.5%] per 10,000/cm and 5.1% [1.6%-9.3%] per 10 microg/m, respectively). For longer averaging times (5 and 15 days), carbon monoxide and nitrogen dioxide were also associated with mortality. There were no clear associations with ozone or sulfur dioxide. CONCLUSION: Exposure to traffic-related air pollution was associated with daily mortality in MI survivors. Point estimates suggest a stronger effect of air pollution in MI survivors than among the general population.

IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies.

Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 -573G>C and type 2 diabetes. The observed association of the IL6 -174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.

Exposure to traffic and the onset of myocardial infarction.

BACKGROUND: An association between exposure to vehicular traffic in urban areas and the exacerbation of cardiovascular disease has been suggested in previous studies. This study was designed to assess whether exposure to traffic can trigger myocardial infarction. METHODS: We conducted a case-crossover study in which cases of myocardial infarction were identified with the use of data from the Cooperative Health Research in the Region of Augsburg Myocardial Infarction Registry in Augsburg, in southern Germany, for the period from February 1999 to July 2001. There were 691 subjects for whom the date and time of the myocardial infarction were known who had survived for at least 24 hours after the event, completed the registry's standardized interview, and provided information on factors that may have triggered the myocardial infarction. Data on subjects' activities during the four days preceding the onset of symptoms were collected with the use of patient diaries. RESULTS: An association was found between exposure to traffic and the onset of a myocardial infarction within one hour afterward (odds ratio, 2.92; 95 percent confidence interval, 2.22 to 3.83; P<0.001). The time the subjects spent in cars, on public transportation, or on motorcycles or bicycles was consistently linked with an increase in the risk of myocardial infarction. Adjusting for the level of exercise on a bicycle or for getting up in the morning changed the estimated effect of exposure to traffic only slightly (odds ratio for myocardial infarction, 2.73; 95 percent confidence interval, 2.06 to 3.61; P<0.001). The subject's use of a car was the most common source of exposure to traffic; nevertheless, there was also an association between time spent on public transportation and the onset of a myocardial infarction one hour later. CONCLUSIONS: Transient exposure to traffic may increase the risk of myocardial infarction in susceptible persons.

Sleep duration and sleep complaints and risk of myocardial infarction in middle-aged men and women from the general population: the MONICA/KORA Augsburg cohort study.

STUDY OBJECTIVES: To examine gender-specific associations between sleep duration and sleep complaints and incident myocardial infarction (MI). DESIGN: Cohort study. SETTING: A representative population sample of middle-aged subjects in Germany. PARTICIPANTS: The study was based on 3508 men and 3388 women (aged 45 to 74 years) who participated in one of the 3 MONICA (Monitoring trends and determinants on cardiovascular diseases) Augsburg surveys between 1984 and 1995, who were free of MI and angina pectoris at baseline and were followed up until 2002. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: A total of 295 cases of incident MI among men and 85 among women occurred during a mean follow-up period of 10.1 years. Compared with women sleeping 8 hours, the multivariable adjusted hazard ratio (HR) of MI among women sleeping < or =5 hours was 2.98 (95% CI, 1.48-6.03), and among women sleeping > or =9 hours 1.40 (95% CI, 0.74-2.64); the corresponding HRs among men were 1.13 (95% CI, 0.66-1.92) and 1.07 (95% CI, 0.75-1.53). In multivariable analysis the relative risk of an incident MI for men and women with difficulties maintaining sleep was 1.12 (95% CI, 0.84-1.48) and 1.53 (95% CI, 0.99-2.37), respectively, and for men and women with difficulties initiating sleep the relative risk was 1.16 (95% CI, 0.82-1.63) and 1.30 (95% CI, 0.81-2.06), respectively. CONCLUSIONS: Modest associations between short sleep duration and difficulties maintaining sleep and incident MI were seen in middle-aged women but not men from the general population.

Head-to-head comparison of BNP and IL-6 as markers of clinical and experimental heart failure: Superiority of BNP.

Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P<0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P<0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P<0.01 vs. CTRL) and LV dysfunction (EF<45%, both P<0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P<0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P<0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P<0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P<0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.

Gene variants of monocyte chemoattractant protein 1 and components of metabolic syndrome in KORA S4, Augsburg.

OBJECTIVE: Monocyte chemoattractant protein 1 (MCP-1) has been suggested to be involved in the development of several components of metabolic syndrome (MetS). The present study investigated the association of nine MCP-1 single nucleotide polymorphisms (SNPs) with MetS, type 2 diabetes mellitus and metabolic risk factors. SUBJECTS AND METHODS: The population-based study sample comprised 1630 subjects aged 55-74 years from KORA S4 (Cooperative Health Research in the Region of Augsburg Survey 4). Genotyping was carried out by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis of allele-dependent primer extension products. RESULTS: The MCP-1 SNP c.-3813C>T exhibited trends for differences between the genotype groups in triglycerides, 2-h glucose and uric acid (P = 0.0084, 0.014, 0.027). Other trends were observed for c.-928G>C associated with height and fasting glucose (P = 0.0024, 0.033), for c.105T>C with height and leukocytes (P = 0.0095, 0.047), for c.*65C>T and c.*3879C>T with MCP-1 levels (both P = 0.012) and for c.-2138A>T with interleukin-6 levels. After correction for multiple testing, none of the analysed SNPs, except c.-928G>C in men showed a significant association with MetS, T2DM or other analysed parameters. Haplotype MCP-1*1 and c.-928G>C in men (P = 0.0002, 0.0004) were significantly associated with an increase in height. CONCLUSIONS: This is the first study to investigate the associations of MCP-1 SNPs with MetS. We found trends for several components of MetS. These parameters were hyperlipidaemia, fasting and 2-h glucose, and uric acid. A new finding is that MCP-1*1 haplotype is associated with height. Further investigation in larger populations is needed to clarify the involvement of MCP-1 in MetS.

Elevated markers of endothelial dysfunction predict type 2 diabetes mellitus in middle-aged men and women from the general population.

OBJECTIVE: Using the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Research in the Region of Augsburg (KORA) database, we investigated prospectively whether increased levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule 1 (sICAM-1), and von Willebrand factor (vWF), all considered to be sensitive markers of endothelial dysfunction, are associated with an increased risk of incident type 2 diabetes mellitus. METHODS AND RESULTS: In a case-cohort study, concentrations of adhesion molecules were measured in stored samples of 532 case subjects and 1712 noncase subjects. VWF was measured in a subsample with available plasma samples (n=191 case and 580 noncase subjects). Men and women with elevated levels of sE-selectin had a significantly increased risk of type 2 diabetes after multivariable adjustment. Hazard ratios (95% CIs) comparing tertile extremes of sE-selectin were 2.63 (1.79 to 3.88) and 1.71 (1.07 to 2.75) for men and women, respectively. Elevated levels of sICAM-1 were also associated with an increased risk of type 2 diabetes; however, the association was not independent of other diabetes risk factors including E-selectin [hazard ratio (95% CI) for tertile 3 versus tertile 1: men, 1.32 (0.89 to 1.96); women, 1.03 (0.64 to 1.67)]. In this study, vWF was not associated with risk of type 2 diabetes. CONCLUSIONS: These data support a role of endothelial dysfunction in the etiology of type 2 diabetes.

Chemokines and incident coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002.

OBJECTIVE: The chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2), interleukin-8 (IL-8/CXCL8), and interferon-gamma-inducible protein-10 (IP-10/CXCL10) have been reported to be involved in the development of atherosclerosis and type 2 diabetes. The aim of this study was to assess whether elevated systemic levels of these chemokines precede coronary events. METHODS AND RESULTS: We investigated MCP-1, IL-8, and IP-10 serum levels in a case-cohort design based on data from 381 individuals (294 men, 87 women) with and 1977 individuals (1006 men, 971 women) without incident coronary heart disease (CHD) from the prospective, population-based MONICA/KORA Augsburg study (1984 to 2002). The mean follow-up time was 11.0 years. Baseline concentrations were significantly higher in cases compared with noncases (P < or = 0.001 for all chemokines). MCP-1 and IL-8 remained associated with CHD risk after adjustment for age, sex, and survey with hazard ratios (95% confidence intervals) comparing extreme tertiles of 1.39 (1.05 to 1.84) for MCP-1 and 1.48 (1.10 to 1.99) for IL-8. However, adjustment for further cardiovascular and immunologic risk factors attenuated the observed associations, and they became nonsignificant. CONCLUSIONS: Elevated systemic levels of the chemokines MCP-1, IL-8, and IP-10 precede CHD but do not represent independent risk factors. Thus, the associations are less pronounced than previously shown for type 2 diabetes.

Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with parameters of left ventricular hypertrophy in men. Results of the MONICA Augsburg echocardiographic substudy.

Angiotensin-converting enzyme (ACE) activity is considered to be of major importance for the conversion of angiotensin (Ang) I to Ang II. Recently, a second ACE, named ACE2, has been identified. Experimental data provide evidence that ACE2 might be involved in modulating cardiac structure and function. In the present explorative study, we assessed whether polymorphisms in the ACE2 gene are related to echocardiographically determined parameters of left ventricular mass, structure or function in the general population. Five intronic single nucleotide polymorphisms (SNPs) were genotyped using the 5'-exonuclease activity (TaqMan) assay in the echocardiographic substudy of the third MONICA Augsburg survey. As ACE2 is located on the X chromosome, women and men were analysed separately. Four SNPs showed high pairwise linkage disequilibrium (rs4646156, rs879922, rs4240157 and rs233575). The minor alleles of these four SNPs were associated with higher left ventricular mass index (LVMI) and higher septal wall thickness (SWT) in men. Likewise, male carriers of a common haplotype (frequency 29.9%) consisting of the minor alleles of these four SNPs displayed higher values for LVMI and SWT than non-carriers (LVMI: TGGC 98.8+/-1.52 vs non-TGGC 94.8+/-0.99 g/m(2), p=0.027; SWT: TGGC 11.5+/-0.14 vs non-TGGC 11.1+/-0.09 mm, p=0.019). Furthermore, this haplotype was associated with an increased odds ratio (OR) for left ventricular hypertrophy (OR 3.10, p=0.006). In women, similar but less pronounced and consistent trends were observed. No association was observed between any of these SNPs and parameters of left ventricular systolic or diastolic function nor with blood pressure levels. This study provides evidence that genetic variants in the ACE2 gene may be associated with left ventricular mass, SWT and left ventricular hypertrophy in hemizygous men.

Living alone is a risk factor for mortality in men but not women from the general population: a prospective cohort study.

BACKGROUND: During the past decades a rising trend of living alone can be observed in the population especially in urban areas. Living alone is considered a psychosocial risk factor. We studied the relationship between living alone, cardiovascular risk factors and mortality. METHODS: We analysed data from the population-based MONICA/KORA cohort study including 3596 men and 3420 women of at least one of three surveys carried out between 1984 and 1995 in the region of Augsburg, Germany. They were between 45 and 74 years old and were followed-up until 31 December 2002. During follow-up 811 men and 388 women died. Cox proportional hazards analysis was used to examine the association between living alone and mortality. RESULTS: Altogether 260 men (7%) and 620 women (18%) were living alone at baseline. Men, who lived alone, were less well educated, had fewer children and friends, and they smoked significantly more than other men. Women, living alone, were also significantly more often current smokers and had less children and friends, but they were more often better educated than cohabitating women. The latter group showed a higher proportion of obese and hypertensive women. Men living alone had a twofold risk to die after multivariable adjustment (hazard ratio = 1.96; p < 0.0001; 95% confidence interval 1.56-2.46). This was not the case for women. CONCLUSION: Living alone is an independent risk factor for mortality in men. It is unclear whether living alone causes an increased mortality or whether predisposition for increased mortality is responsible for men living alone.

Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities.

BACKGROUND: Ambient air pollution has been associated with increases in acute morbidity and mortality. The objective of this study was to evaluate the short-term effects of urban air pollution on cardiac hospital readmissions in survivors of myocardial infarction, a potentially susceptible subpopulation. METHODS AND RESULTS: In this European multicenter cohort study, 22,006 survivors of a first myocardial infarction were recruited in Augsburg, Germany; Barcelona, Spain; Helsinki, Finland; Rome, Italy; and Stockholm, Sweden, from 1992 to 2000. Hospital readmissions were recorded in 1992 to 2001. Ambient nitrogen dioxide, carbon monoxide, ozone, and mass of particles <10 microm (PM10) were measured. Particle number concentrations were estimated as a proxy for ultrafine particles. Short-term effects of air pollution on hospital readmissions for myocardial infarction, angina pectoris, and cardiac causes (myocardial infarction, angina pectoris, dysrhythmia, or heart failure) were studied in city-specific Poisson regression analyses with subsequent pooling. During follow-up, 6655 cardiac readmissions were observed. Cardiac readmissions increased in association with same-day concentrations of PM10 (rate ratio [RR] 1.021, 95% CI 1.004 to 1.039) per 10 microg/m3) and estimated particle number concentrations (RR 1.026 [95% CI 1.005 to 1.048] per 10,000 particles/cm3). Effects of similar strength were observed for carbon monoxide (RR 1.014 [95% CI 1.001 to 1.026] per 200 microg/m3 [0.172 ppm]), nitrogen dioxide (RR 1.032 [95% CI 1.013 to 1.051] per 8 microg/m3 [4.16 ppb]), and ozone (RR 1.026 [95% CI 1.001 to 1.051] per 15 microg/m3 [7.5 ppb]). Pooled effect estimates for angina pectoris and myocardial infarction readmissions were comparable. CONCLUSIONS: The results suggest that ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in 5 European cities.

Body fat distribution and risk of type 2 diabetes in the general population: are there differences between men and women? The MONICA/KORA Augsburg cohort study.

BACKGROUND: It remains controversial whether body mass index (BMI), waist circumference (WC), or waist-hip ratio (WHR) is a better risk predictor of type 2 diabetes. OBJECTIVE: The objective was to examine the sex-specific relevance of WC, WHR, and BMI to the development of type 2 diabetes. DESIGN: The prospective population-based cohort study was based on 3055 men and 2957 women aged 35-74 y who participated in the second (1989-1990) or third (1994-1995) MONICA (Monitoring Trends and Determinants on Cardiovascular Diseases) Augsburg survey. The subjects were free of diabetes at baseline. Hazard ratios (HRs) were estimated from Cox proportional hazards models. RESULTS: During a mean follow-up of 9.2 y, 243 cases of incident type 2 diabetes occurred in men and 158 occurred in women. Multivariable-adjusted HRs across quartiles of BMI were 1.0, 1.37, 2.08, and 4.15 in men and 1.0, 3.77, 4.95, and 10.58 in women; those of WC were 1.0, 1.15, 1.57, and 3.40 in men and 1.0, 3.21, 3.98, and 10.70 in women; those of WHR were 1.0, 1.14, 1.80, and 2.84 in men and 1.0, 0.82, 2.06, and 3.51 in women. In joint analyses, the highest risk was observed in men and women with a high BMI in combination with a high WC and a high WHR. CONCLUSIONS: Both overall and abdominal adiposity were strongly related to the development of type 2 diabetes. Because there was an additive effect of overall and abdominal obesity on risk prediction, WC should be measured in addition to BMI to assess the risk of type 2 diabetes in both sexes.

Regional disparities of hypertension prevalence and management within Germany.

OBJECTIVE: To investigate regional variations in the prevalence and management of hypertension in two communities in the north-east and the south-west of Germany. STUDY SETTING: Two population-based surveys of men and women aged 25-74 years, using a common standardized protocol: the Study of Health in Pomerania (SHIP; 3744 participants) and the Kooperative Gesundheitsforschung in der Region Augsburg (KORA; 4224 participants). MAIN OUTCOME MEASURES: Comparison of SHIP and KORA with regard to mean systolic (SBP) and diastolic blood pressure (DBP), prevalence of hypertension, percentage of awareness, treatment and control of hypertension in the community, by age and sex. RESULTS: The overall age-standardized prevalence of hypertension for men was 60.1% in SHIP and 41.4% in KORA; the corresponding values for women were 38.5 and 28.6%. Mean blood pressure differences were present in each 10-year age group and sex. The overall SBP difference between SHIP and KORA was 8.2 mmHg (95% confidence interval 7.2-9.3) in men and 6.3 mmHg (5.3-7.3) in women, the respective DBP differences were 3.8 mmHg (3.2-4.5) and 3.6 mmHg (3.0-4.2). Nevertheless, the percentage of awareness, treatment and control of hypertension was strikingly similar in the two studies (women, P = 0.858; and men, P = 0.564). CONCLUSIONS: The entire distribution of diastolic and systolic blood pressure values was shifted upwards in the north-eastern as compared to the south-western German population samples and the prevalences of hypertension differed accordingly. Despite such substantial epidemiologic differences, the community management of hypertension was of almost identical quality.

Association of cardiovascular risk factors with markers of endothelial dysfunction in middle-aged men and women. Results from the MONICA/KORA Augsburg Study.

Endothelial dysfunction plays an important role in the pathogenesis of cardiovascular diseases and diabetes mellitus. However, the causes underlying endothelial dysfunction are not fully understood. Therefore, the aim of the present study was to investigate associations of cardiovascular risk factors with soluble adhesion molecules (sE-Selectin, sICAM-1), soluble thrombomodulin (sTM) and von Willebrand factor (vWF) as markers of endothelial dysfunction. The study population consisted of a subcohort of 2,168 men and women aged 35 to 74 years randomly drawn from three cross-sectional population-based MONICA/KORA Augsburg surveys conducted between 1984 and 1995. In multivariable linear regression analysis, current smoking, high (versus moderate) alcohol consumption, ratio of total cholesterol/HDL-cholesterol (TC/HDL-C) and C-reactive protein (CRP) were significantly associated with elevated levels of sE-selectin and sICAM-1. Increased levels of sE-selectin were also found in subjects with actual hypertension, high body mass index and prevalent diabetes mellitus. In addition, low physical activity and no (versus moderate) alcohol consumption were significantly associated with elevated concentrations of sICAM-1. Levels of sTM were higher in subjects with actual hypertension, no or high amounts of alcohol intake and a high ratio of TC/HDL-C, but were lower in subjects with a history of myocardial infarction. VWF was significantly associated with CRP only. In conclusion, sE-selectin and sICAM-1 are more strongly associated with traditional cardiovascular risk factors than sTM and vWF.

Comparison of different methods in analyzing short-term air pollution effects in a cohort study of susceptible individuals.

BACKGROUND: Short-term fluctuations of ambient air pollution have been associated with exacerbation of cardiovascular disease. A multi-city study was designed to assess the probability of recurrent hospitalization in a cohort of incident myocardial infarction survivors in five European cities. The objective of this paper is to discuss the methods for analyzing short-term health effects in a cohort study based on a case-series. METHODS: Three methods were considered for the analyses of the cohort data: Poisson regression approach, case-crossover analyses and extended Cox regression analyses. The major challenge of these analyses is to appropriately consider changes within the cohort over time due to changes in the underlying risk following a myocardial infarction, slow time trends in risk factors within the population, dynamic cohort size and seasonal variation. RESULTS: Poisson regression analyses, case-crossover analyses and Extended Cox regression analyses gave similar results. Application of smoothing methods showed the capability to adequately model the complex time trends. CONCLUSION: From a practical point of view, Poisson regression analyses are less time-consuming, and therefore might be used for confounder selection and most of the analyses. However, replication of the results with Cox models is desirable to assure that the results are independent of the analytical approach used. In addition, extended Cox regression analyses would allow a joint estimation of long-term and short-term health effects of time-varying exposures.

Performance of screening questionnaires and risk scores for undiagnosed diabetes: the KORA Survey 2000.

BACKGROUND: Validation of published screening questionnaires and risk scores for undiagnosed diabetes has typically not been performed in independent population samples. METHODS: Oral glucose tolerance tests were performed in 1353 participants (aged 55-74 years) without known diabetes in the Cooperative Health Research in the Region of Augsburg (KORA) Survey 2000, Augsburg, Germany. Sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) for undiagnosed diabetes were calculated for various screening questionnaires. RESULTS: Four screening tests (Rotterdam Diabetes Study, Cambridge Risk Score, San Antonio Heart Study, and Finnish Diabetes Risk Score) were applied to the KORA data. The AUCs were 61% (95% confidence interval [CI], 56%-66%) for the Rotterdam Diabetes Study, 65% (95% CI, 60%-69%) for the Finnish Diabetes Risk Score (P=.10 vs Rotterdam), and 67% (95% CI, 62%-72%) for the Cambridge Risk Score (P<.001 vs Rotterdam). A predictive model including fasting glucose level (San Antonio Heart Study) yielded an AUC of 90% (P<.01 vs all 3 questionnaires); however, this was not significantly different from fasting glucose level alone (AUC, 89%; P=.46). The sensitivities, specificities, and predictive values of questionnaires were substantially lower than originally described, which was mainly due to population variation of risk factors compared with the KORA sample (age, body mass index, antihypertensive medication, and smoking). CONCLUSIONS: Currently proposed questionnaires yielded low validity when applied to a new population, most likely due to differences in population characteristics. Performance of diabetes risk questionnaires or scores must be assessed in the target population where they will be applied.

[Epidemiology and demographic evolution exemplified for cardiovascular diseases in Germany]. / Epidemiologie und demographische Entwicklung am Beispiel kardiovaskulärer Erkrankungen in Deutschland.

The interplay between demographic and epidemiologic evolutions is presented exemplified for cardiovascular diseases in Germany. The actually 82 million inhabitants of Germany build the frame for disease occurrence; currently, 2.1 million men and 4.4 million women are > or = 75 years old. The ongoing increase of life expectancy to 75.6 years in men and 81.3 years in women was associated with a remarkable decrease of cardiovascular and ischemic heart disease (IHD) mortality and an increasing disease-specific mean age of death. Each third male and each fourth female death from IHD could be prevented, whereas the absolute number of nonfatal acute myocardial infarction (AMI) increased in the younger ages and decreased in the higher age groups. Since 1985, the total number of fatal and nonfatal cases of AMI has decreased by 24% in men and by 22% in women; two thirds of male and one third of female cases occur before the 75th year of age. These positive trends are mainly the result of a more effective acute and long-term therapy after AMI onset. Actually, 35% of all AMI patients do not survive the first day after acute onset and in up to 90% of them classic risk factors (hypertension, dyslipidemia, diabetes, cigarette smoking) were present. Therefore, the theme number 1 for the population must be intensified activities of primary prevention.

C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany.

BACKGROUND: The Framingham Coronary Heart Disease (CHD) prediction score is recommended for global risk assessment in subjects prone to CHD. Recently, C-reactive protein (CRP) has emerged as an independent predictor of CHD. We sought to assess the potential of CRP measurements to enhance risk prediction based on the Framingham Risk Score (FRS) in a large cohort of middle-aged men from the general population. METHODS AND RESULTS: We measured CRP and traditional cardiovascular risk factors at baseline in 3435 white men of German nationality, 45 to 74 years of age. All men were drawn from 3 random samples of the general population in the Augsburg area located in Southern Germany in 1984 to 1985, 1989 to 1990, and 1994 to 1995 (response rate, 80%), and the FRS was calculated in all of them. Outcome was defined as nonfatal and fatal coronary events, including sudden cardiac death. During an average follow-up of 6.6 years, a total of 191 coronary events occurred. Cox regression showed a significant contribution of CRP to coronary event risk prediction independent of the FRS (P=0.0002). In stratified analysis for 5 categories of FRS, CRP significantly added prognostic information to the FRS in subjects in 2 intermediate risk categories (P=0.03 and P=0.02). CONCLUSIONS: Our results suggest that CRP enhances global coronary risk as assessed by the FRS, especially in intermediate risk groups. This might have implications for future risk assessment.

Lipoprotein-associated phospholipase A2 adds to risk prediction of incident coronary events by C-reactive protein in apparently healthy middle-aged men from the general population: results from the 14-year follow-up of a large cohort from southern Germany.

BACKGROUND: Chronic inflammation represents an essential feature of the atherosclerotic process. Lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme mainly produced by monocytes/macrophages, generates potent proinflammatory products. METHODS AND RESULTS: Plasma concentrations of Lp-PLA2 were determined by ELISA in 934 apparently healthy men aged 45 to 64 years sampled from the general population in 1984 and followed up until 1998. During this period, 97 men experienced a coronary event diagnosed according to the MONICA (MONItoring of trends and determinants in CArdiovascular disease) protocol. Baseline levels of Lp-PLA2 were higher in subjects who experienced an event than in event-free subjects (295+/-113 versus 263+/-79 ng/mL, P<0.01). Lp-PLA2 was positively correlated with total cholesterol (R=0.30, P<0.0001) and age (R=0.12, P=0.001), was only slightly correlated with HDL cholesterol (R=0.09, P=0.005) and C-reactive protein R=0.06, P=0.06), but was not correlated with body mass index or blood pressure. In a Cox model, a 1-SD increase in Lp-PLA2 was associated with risk of future coronary events (hazard ratio [HR] 1.37, 95% CI 1.16 to 1.62). After controlling for potential confounders, the HR was attenuated but remained statistically significant (HR 1.23, 95% CI 1.02 to 1.47). Further inclusion of C-reactive protein in the model did not appreciably affect its predictive ability (HR 1.21, 95% CI 1.01 to 1.45). CONCLUSIONS: Elevated levels of Lp-PLA2 appeared to be predictive of future coronary events in apparently healthy middle-aged men with moderately elevated total cholesterol, independent of CRP. This suggests that Lp-PLA2 and CRP may be additive in their ability to predict risk of coronary heart disease.

Association of polymorphisms of the apolipoprotein(a) gene with lipoprotein(a) levels and myocardial infarction.

BACKGROUND: Serum lipoprotein(a) [Lp(a)] concentration is largely determined by variability at the apolipoprotein(a) gene locus. Most prominent effects relate to polymorphisms in the promoter (a pentanucleotide [PN] repeat) and coding regions (a kringle IV [K4] repeat), the latter of which also affects Lp(a) particle size. The impact of these polymorphisms on cardiovascular risk is poorly understood. METHODS AND RESULTS: We studied both polymorphisms and Lp(a) levels in 834 registry-based myocardial infarction (MI) patients (38% women) and 1548 population-based controls. Lp(a) concentrations were inversely related with the numbers of K4 and PN repeats. However, the effect of the PN polymorphism was restricted to subjects producing small Lp(a) particles (8 PN 8.7 mg/dL; P<0.0001). The odds to present with MI were elevated in individuals producing small Lp(a) particles (