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BACKGROUND: Of the numerous emerging biomarkers for coronary heart disease (CHD), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an enzyme involved in lipid metabolism and inflammatory pathways, seems to be a promising candidate. Implementation of Lp-PLA(2) measurement into clinical practice, however, requires data on the reliability of such measurements. METHODS: We measured Lp-PLA(2) concentrations by ELISA in blood samples drawn from 200 post-myocardial infarction patients (39-76 years) at 6 monthly intervals between May 2003 and February 2004, for a total of 1143 samples. We estimated analytical, within-individual, and between-individual variation, the critical difference, and the intraclass correlation coefficient of reliability (ICC) to assess the reliability of serial Lp-PLA(2) measurements. RESULTS: The mean (SD) plasma Lp-PLA(2) concentration for the study participants was 188.7 (41.8) microg/L, with no significant difference between men and women. The analytical CV for Lp-PLA(2) was 4.4%, the within-individual biological CV was 15%, and the between-individual CV was 22%. The ICC was 0.66. An important part of the total variation in plasma Lp-PLA(2) concentration was explained by the between-individual variation (as a percentage of the total variance, 66.1%), whereas the within-individual variance was 31.3%. The analytical variance was as low as 2.6%. CONCLUSIONS: Between-individual variation in Lp-PLA(2) concentration was substantially greater than within-individual variation. In general, our data demonstrate considerable stability and good reproducibility of serial Lp-PLA(2) measurements, results that compared favorably with those for the more commonly measured lipid markers.

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Ischaemic heart disease (IHD) has changed from a disease of middle-aged men in the late 1970s to a disease of elderly women in the 2000s. Most clinical studies during the past three decades have been conducted with men. Cardiac rehabilitation programmes were also developed with special regard to improving the rate of return to work in middle-aged men. The rehabilitation needs of older patients and women in particular have been largely neglected. The aim of this review is briefly to outline our present knowledge on gender issues in cardiac rehabilitation, and to specify barriers with regard to physical activities especially in (older) women. Coping with a cardiac event, women tend to minimize or play down the impact of their health situation and avoid burdening their social contacts. After a first cardiac event, women report greater psychological distress and lower self-efficacy and self-esteem. In addition, older age, lower exercise levels and reduced functional capacity or co-morbid conditions such as osteoporosis and urinary incontinence are barriers to physical activities in women with IHD. Recent studies on psychosocial intervention revealed less favourable results in women compared with men. These findings have not yet been well explained. This emphasizes our current lack of knowledge about the processes and determinants of successful psychosocial interventions in men and women with IHD. A large (European) trial on gender-specific coping styles, needs, and preferences of older women, and the effects of psychosocial intervention is proposed.

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INTRODUCTION: Patients with diabetes mellitus (DM) have an unfavorable prognosis after myocardial infarction (MI), partially due to a higher risk of sudden cardiac death (SCD). QT dynamicity is an independent predictor of SCD in post-MI patients. However, the effects of diabetes on QT dynamicity in patients with MI have not been described. METHODS: We studied 468 survivors of MI (67 with DM) from the population-based MONICA registry (KORA Family Heart Study), Augsburg, Germany, by standardized questionnaire, anthropometry, electrocardiogram (ECG), 30-minute-Holter-ECG-recordings and echocardiography. In addition, 422 siblings without prior MI (22 with DM) were studied by the same protocol. RESULTS: Among post-MI patients, the QT/RR slope was significantly steeper in diabetics than in nondiabetics (0.096 +/- 0.057 vs 0.077 +/- 0.045; P = 0.002). Likewise, among siblings without MI, the QT/RR slope was steeper in diabetics than in nondiabetics (0.104 +/- 0.053 vs 0.080 +/- 0.042; P = 0.008). The association of DM with steeper QT/RR slope remained significant in multivariate models in post-MI patients (beta: -0.14; P = 0.004) as well as in individuals without MI (beta: -0.10; P = 0.047). CONCLUSIONS: In a large population of survivors of MI and unaffected siblings, patients and siblings presenting with DM exhibited an abnormal QT rate-dependence, compared with individuals without DM in both groups. Thus, diabetes itself may be a major determinant of ventricular arrhythmias, independently of a previous MI. These observations might in part explain the higher incidence of sudden cardiac death and ventricular arrhythmias in patients with DM.

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OBJECTIVE: Survivors of myocardial infarction (MI) are known to have a high prevalence of arterial hypertension which, at the same time, imposes a major risk to such patients. Genetic variants of the arachidonic acid monooxygenase CYP4A11 may result in decreased synthesis of 20-hydroxyeicostatetraenoic acid (20-HETE), experimental hypertension and elevated blood pressure levels in humans. The present study aimed to investigate the impact of the functionally relevant T8590C polymorphism of this gene on blood pressure and the prevalence of hypertension in MI patients. METHODS: Survivors of MI from the MONICA Augsburg MI registry (n = 560) were studied after a mean of 5.6 years after the acute event. Participants were examined by standardized anthropometric and echocardiographic measurements, as well as genotyping for CYP4A11 T8590C allele status. RESULTS: Genotype frequencies in MI patients (TT = 71.8%, CT = 26.2%, CC = 2.0%) did not differ from those in population-based controls (n = 1363; TT = 75.4%, CT = 22.5% and CC = 2.1%, P = 0.22). MI survivors with the CC genotype displayed higher systolic blood pressure levels (CC: 143.4 +/- 4.9 mmHg versus CT: 134.5 +/- 1.3 mmHg and TT: 131.1 +/- 0.8 mmHg; P = 0.02) and a non-significant trend towards higher diastolic blood pressure levels (CC: 88.4 +/- 3.0 mmHg versus CT: 84.9 +/- 0.8 mmHg and TT: 83.9 +/- 0.5 mmHg; P = 0.17) in multivariate models. Accordingly, the C allele was related to elevated odds ratios for hypertension in a recessive [4.14; 95% confidence interval (CI) = 1.07-15.96, P = 0.04] and in a dominant model (1.50; 95% CI = 1.03-2.20, P = 0.04), respectively. No blood pressure-independent association of the T8590C polymorphism with echocardiographic parameters of left ventricular function and/or geometry was found. CONCLUSION: The data obtained in the present study strengthen the evidence of an association of the CYP4A11 T8590C polymorphism with blood pressure levels and hypertension prevalence. Particularly, the risk of arterial hypertension is substantially higher in MI patients homozygous for the CC allele. By contrast, no evidence was obtained for an association between this genotype and MI.

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OBJECTIVE: We performed a prospective case-cohort study in initially healthy, middle-aged men and women from the MONICA/KORA Augsburg studies conducted between 1984 and 2002 to assess the role of IL-18 in comparison with IL-6 and CRP in the prediction of incident coronary heart disease (CHD). METHODS AND RESULTS: Concentrations of IL-18 were measured in 382 case subjects with incident CHD and 1980 noncases. Mean follow-up was 11 years. Baseline concentrations of IL-18 were slightly higher in cases than in noncases (172.4 [1.0] versus 161.3 [1.0] pg/mL, respectively; P=0.114), but were clearly elevated for C-reactive protein (CRP) and IL-6 in cases compared with noncases. In multivariable analyses, accounting for classical cardiovascular risk factors and inflammatory markers, no statistically significant association was seen between increased concentrations of IL-18 and incident CHD both in men (hazard ratio [HR] and 95% confidence intervals [CIs] comparing extreme tertiles, 1.20; 95% CI, 0.85 to 1.69), and in women (HR, 1.25; 95% CI, 0.67 to 2.34). However, in this population increased concentrations of CRP and IL-6 were found to be independent predictors of future CHD events, even after multivariable adjustment. CONCLUSIONS: Elevated concentrations of CRP and IL-6, but not IL-18, were independently associated with risk of CHD in subjects from an area with moderate absolute risk.

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BACKGROUND: Even mild renal dysfunction is a predictor of cardiovascular morbidity. We investigated whether sub-threshold microalbuminuria or mildly decreased estimated glomerular filtration rate (eGFR) are related to left ventricular hypertrophy (LVH) in the general population. METHODS: Urinary albumin-to-creatinine ratio (UACR) served to determine albuminuria, eGFR was estimated using modification of diet in renal disease (MDRD) formula, and LV geometry was assessed echocardiographically in the third MONItoring of trends and determinants in CArdiovascular disease/Cooperative Health Research in the Augsburg Area (MONICA/KORA) Augsburg survey (n = 1187). RESULTS: The prevalence of LVH increased in parallel with UACR. Compared with the first tertile of this normal population, the age, systolic blood pressure (SBP), body mass index, gender and diabetes adjusted odds ratio (OR) for LVH was elevated already in the second (4.32-8.75 mg/g in men; 4.60-9.48 mg/g in women; OR: 2.10, P = 0.001) as well as in the third UACR-tertile (> or =8.76 mg/g in men; > or =9.49 mg/g in women; OR: 1.63, P = 0.035). Likewise, adjusted SBP increased with UACR-tertiles [129 vs 132 (P = 0.036) and 137 mmHg (P < 0.001) in the first, second and third tertile, respectively], whereas diastolic blood pressure was significantly elevated only in the third UACR-tertile [79 vs 80 and 81 mmHg (P = 0.002) in the tertiles, respectively]. In contrast, tertiles of eGFR or mildly impaired eGFR (<90 ml/min/1.73 m(2)) were not associated with the prevalence of LVH in multivariate models. CONCLUSIONS: At the general population level, even low-grade albuminuria is associated with LVH. Thus, the conventional UACR-threshold of microalbuminuria (30 mg/g) may be too conservative given that end organ damage such as LVH is observed with increased frequency at much lower levels.

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Genetic variants of the arachidonic acid monooxygenase CYP4A11 result in decreased synthesis of 20-hydroxyeicostatetraenoic acid and experimental hypertension. Moreover, in humans, the T8590C polymorphism of CYP4A11 displayed association with arterial hypertension. The aim of the present study was to further investigate this association in a large population-based sample. Therefore, the participants of the echocardiographic substudy of the third MONICA (MONitoring trends and determinants In CArdiovascular disease) survey (n=1397) were studied by standardized anthropometric, echocardiographic, and biochemical measurements as well as genotyping for CYP4A11 T8590C allele status. Individuals with the CC genotype have higher systolic (CC 141.4+/-3.17 mm Hg versus CT 134.2+/-0.97 mm Hg and TT 134.3+/-0.53 mm Hg; P=0.03) and diastolic blood pressure levels (CC 85.4+/-2.06 mm Hg versus CT 80.3+/-0.63 mm Hg and TT 80.7+/-0.34 mm Hg; P=0.02). Accordingly, the odds ratio (adjusted for age, body mass index, and gender) of the CC genotype versus the CT and TT genotypes for hypertension was 3.31 (95% confidence interval [CI]), 1.38 to 7.96; P=0.016) in the entire study population, with similar trends in men (4.30 [95% CI, 1.08 to 17.15]) and women (2.93 [95% CI, 0.88 to 9.84]). Consistent with the renal effects of the gene, no blood pressure-independent association between the T8590C polymorphism and echocardiographic parameters of left ventricular function and geometry was found. In conclusion, our data strengthen the association between the T8590C polymorphism of CYP4A11 and hypertension and suggest a recessive mode of inheritance. In contrast, we found no blood pressure-independent modulatory effect of CYP4A11 T8590C on cardiac size, structure, and function.

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BACKGROUND: Oxidized LDL (oxLDL) is thought to play a key role in the inflammatory response in the arterial vessel wall. METHODS AND RESULTS: In a prospective, nested, case-control study, the association between plasma oxLDL and risk of an acute coronary heart disease (CHD) event was investigated in men without prevalent CHD or diabetes mellitus at baseline. Subjects came from 2 population-based MONICA/KORA Augsburg surveys conducted in the years 1989-1990 and 1994-1995 with follow-up in 1998 (mean+/-SD follow-up time, 5.6+/-2.6 years). OxLDL was determined by ELISA in 88 men with incident CHD and in 258 age- and survey-matched controls. Hazard ratios (HRs) were estimated from conditional logistic-regression models with matching for age and survey. Baseline mean plasma oxLDL concentrations were significantly higher in subjects who subsequently experienced an event compared with controls (mean+/-SD, 110+/-32 versus 93+/-28 U/L; P< or =0.001). After adjustment for smoking, hypertension, obesity, physical activity, education, and alcohol consumption, the HR for a future CHD event in a comparison of the upper tertile of the oxLDL distribution with the lower tertile was 4.25 (95% confidence interval, 2.09 to 8.63; P<0.001). Plasma oxLDL was the strongest predictor of CHD events compared with a conventional lipoprotein profile and other traditional risk factors for CHD. When both oxLDL and C-reactive protein were simultaneously assessed in the same model, they still predicted future CHD events even after multivariable adjustment. CONCLUSIONS: Elevated concentrations of oxLDL are predictive of future CHD events in apparently healthy men. Thus, oxLDL may represent a promising risk marker for clinical CHD complications and should be evaluated in further studies.

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AIMS: To investigate the association between apolipoprotein B (apoB), A-I (apoA-I), the apoB/apoA-I ratio, and the incidence of coronary events. METHODS AND RESULTS: Analysis included 1414 men and 1436 women aged 35-64 years without a prior coronary event who participated in the population-based MONICA Augsburg survey 1984-85 (median followed-up period 13 years). Incidence of fatal and non-fatal myocardial infarction, and sudden cardiac death was assessed using data of the MONICA/KORA Augsburg coronary event registry. During follow-up, 114 incident coronary events occurred in men and 31 in women. In multivariable analysis, an increase of 1 standard deviation in the serum concentration of apoB was associated with an increased risk of coronary events in men [hazard ratio (HR)=1.49; 95% confidence interval (CI); 1.25-1.78] and in women (HR=1.73; 95% CI; 1.32-2.27). By contrast, elevated concentrations of apoA-I were not associated with a significantly decreased risk of coronary events in either sex (HR=0.91). Furthermore, the predictive power of the apoB/apoA-I ratio was similar to that of the total cholesterol/HDL cholesterol ratio in men and women. CONCLUSION: ApoB and the apoB/apoA-I ratio were strong predictors of coronary events in middle-aged men and women, whereas apoA-I did not add significantly to the estimation of future coronary risk.

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BACKGROUND: Recently, a polymorphism at position -174 (G>C) of the interleukin-6 (IL-6) promoter was found to be associated with an increased prevalence of myocardial infarction (MI). The aim of the present study was to further investigate the association of the IL-6 -174 G/C allele status with specific end organ damage, i.e. myocardial infarction in large population-based samples. METHODS: Individuals from two Bavarian samples of MI patients (total n=1322) and the population-based Augsburg MONICA survey (1023 unselected controls) were studied by questionnaire, physical examination, echocardiographical assessment and biochemical analyses. The -174 G/C polymorphism was genotyped using a newly established PCR-RFLP. IL-6 levels were measured in a subset of 574 MI patients. RESULTS: In the population-based sample, the IL-6 genotype was neither associated with traditional cardiovascular risk factors (systolic and diastolic blood pressure, total cholesterol, HDL and LDL cholesterol, body mass index, diabetes mellitus) nor with cardiac structural or functional parameters (left ventricular mass index, ejection fraction, diastolic inflow pattern). Moreover, the genotype distribution of the -174 G/C polymorphism was not different in MI patients (GG: 34.1%; GC: 47.4%; CC: 18.5%) and population-based controls (GG: 32.4%; GC: 48.8%; CC: 18.9%) (p=0.67). IL-6 levels were neither related to the -174 G/C polymorphism (p=0.29) nor to ACE-inhibitor treatment (2.16 with vs. 2.09 pg/ml without ACE-inhibitor, p=0.27). However, patients receiving statins displayed significantly lower IL-6 levels (1.83 vs. 2.32 pg/ml in the group without statins, p<0.0001). CONCLUSIONS: This extensive investigation failed to obtain evidence that the IL-6 -174 G/C promoter polymorphism affects traditional cardiovascular risk factors or the prevalence of myocardial infarction in a Caucasian sample.

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OBJECTIVE: To investigate the relationship between body weight and the use of health care services among women from southern Germany. RESEARCH METHODS AND PROCEDURES: Data were drawn from the 1994 to 1995 Monitoring of Trends and Determinants in Cardiovascular Disease Augsburg survey, covering a population-representative sample of women 25 to 74 years old (n = 2301). Logistic regression models were used to calculate odds ratios (ORs) for the use of medical services by women with overweight (BMI 25.0 to 29.9 kg/m(2)) or obesity (BMI >or= 30 kg/m(2)) in comparison with normal-weight women (BMI < 25.0 kg/m(2)). RESULTS: In multivariable analysis, obese women 50 to 74 years old were more likely than normal-weight women to delay cancer screening procedures, such as manual breast examination and Papanicolaou smear (OR 0.52, 95% confidence interval 0.37 to 0.74) in the previous 12 months. However, the relationship between obesity and cancer screening was not found to be significant in 25- to 49-year-old women (OR 0.92, 95% confidence interval 0.62 to 1.36). Neither in the 25- to 49-year-old age group nor in the 50- to 74-year-old age group were independent relationships between higher body weight and total physician visits, hospitalizations, or medication use observed. DISCUSSION: Obese women tended to use medical services with greater frequency due to obesity-related diseases. However, postmenopausal women with a BMI >or= 30 kg/m(2) were more likely to delay routine cancer screening, putting them at a greater risk for death from breast, cervical, and endometrial cancer. Thus, obese postmenopausal women should be targeted for increased screening.

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