Glycated apolipoprotein B and myocardial infarction

AimsTo evaluate the association of serum concentrations of glycated apolipoprotein B (ApoBg) with the incidence of myocardial infarction (MI) in subjects with and without diabetes.MethodsThe design is a nested case-control study. The cohort included 5632 subjects over 50 years of age attending the clinical laboratories of a small geographic area in southern Italy. After five years, 4563 subjects were traced and 103 had developed MI. We sampled from the cohort two controls for each incident case of MI, frequency matched for sex and diabetes. ApoBg was measured using a monoclonal antibody. Logistic regression was used for statistical analysis of the data.ResultsApoBg at baseline was higher in subjects who developed myocardial infarction than in controls in both non-diabetic and diabetic subjects (t test, P = 0.009 and P = 0.05 respectively). MI odds ratio in the third tertile of ApoBg was 2.01 (95 % CI 0.93–4.33) in non-diabetic and 2.88 (0.85–9.68) in diabetic subjects (chi-square test for trend; non-diabetics P = 0.03, diabetics P = 0.06). Serum triglycerides, cholesterol, HDL and LDL cholesterol, glucose and insulin were not associated with MI (P > 0.10).ConclusionApoBg at baseline is directly associated with the development of MI in the following five years in both diabetic and non-diabetic individuals.     

Association of sports activities in leisure time and incident myocardial infarction in middle-aged men and women from the general population: the MONICA/KORA Augsburg cohort study.

BACKGROUND: To examine sex-specific associations between sports activities in leisure time and incident myocardial infarction (MI) in a representative population sample in Germany. DESIGN: Cohort study. METHODS: The study was based on 3501 men and 3475 women (aged 45-74 years) who participated in one of the three MONICA Augsburg surveys between 1984 and 1995 and were followed up until 2002. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. RESULTS: A total of 295 cases of incident MIs among men and 91 among women were registered during a median follow-up period of 8.6 years. In both sexes, moderate and high level of sports activities in leisure time were associated with a reduced risk of incident MI after age and survey adjustment; the HRs of MIs associated with a moderate and high level of sports activities in leisure time were 0.68 (0.49-0.96), and 0.71 (0.50-0.99) for men and 0.42 (0.21-0.84), and 0.18 (0.04-0.74) for women. Further adjustment for other major coronary heart disease risk factors attenuated the HRs: in moderately and highly active men, the HRs were not significant anymore (HRs 0.78 and 0.84, respectively), but the HRs remained significantly reduced in moderately and highly active women (HR 0.49; 95% CI, 0.24-1.00 and HR 0.21; 95% CI, 0.05-0.87, respectively). CONCLUSION: Moderate or high levels of sports activities in leisure time are associated with a significantly reduced risk of MI in women, but not men from the general population.     

Macrophage migration inhibitory factor (MIF) and risk for coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002

Objective

Macrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity, has been reported to contribute to the development of cardiovascular disease. MIF is expressed in atherosclerotic lesions in humans, and gene deletion and antibody inhibition studies in animal models indicated that MIF may be cause rather than consequence of atherosclerosis. We sought to assess the triangular association between MIF genotypes, circulating MIF levels and risk for incident coronary heart disease (CHD) in the large, prospective, population-based MONICA/KORA case-cohort study (Augsburg, Southern Germany).

Methods

MIF genotypes, haplotypes and serum concentrations were determined in 363 individuals with incident CHD and 1908 individuals without CHD during follow-up (mean follow-up time 10.3 years).

Results

Circulating MIF concentrations were not associated with the risk for CHD. In women, carriers of the minor alleles rs755622C and rs2070766G had a higher risk for incident CHD, and a haplotype that contained these two minor alleles was significantly associated with increased risk for CHD (HR 2.44, 95%CI 1.30–4.59).

Conclusion

The lack of association between serum levels and incident CHD indicates that MIF may not be a novel biomarker for CHD risk. However, the association of a haplotype containing the rs755622C allele, which has been reported before to increase the susceptibility for various other proinflammatory conditions, with CHD points towards a role for MIF in local vascular inflammation and atherogenesis.     

Framingham risk function overestimates risk of coronary heart disease in men and women from Germany--results from the MONICA Augsburg and the PROCAM cohorts.

BACKGROUND: The prediction of the absolute risk of coronary heart disease (CHD) is commonly based on risk prediction equations that originate from the Framingham Heart Study. However, differences in population risk levels compromise the external validity of these risk functions. SETTING AND STUDY POPULATION: Participants aged 35-64 years from the MONICA Augsburg (2861 men and 2925 women) and the PROCAM (5527 men and 3155 women) cohorts were followed-up with regard to incident non-fatal myocardial infarction (MI) and fatal coronary events. For each participant, the predicted absolute risk of fatal plus non-fatal events was derived using Framingham risk equations. Predicted and actually observed risks were compared. RESULTS: The two cohorts were similar in their baseline characteristics. Coronary risk predicted by the Framingham risk function substantially exceeded the risk actually observed in the German cohorts, irrespective of gender. The difference between predicted and observed absolute CHD risk increased with age while the ratio of predicted over observed risk remained constant at about a value of 2. Taking potentials for underascertainment in the German cohorts due to unrecognised MI and sudden deaths into account, the residual magnitude of risk overestimation by the Framingham risk function is probably at least 50%. CONCLUSIONS: Local guidelines for the management of patients with risk factors need to correct for this overestimation to avoid inadequate initiation of treatment and inflation of costs in primary prevention. Similar studies should be conducted in other populations with the aim of defining appropriate factors that calibrate absolute risk predictions to local population levels of CHD risk.     

Myeloperoxidase is associated with incident coronary heart disease independently of traditional risk factors: results from the MONICA/KORA Augsburg study

Abstract. Karakas M, Koenig W, Zierer A, Herder C, Rottbauer W, Baumert J, Meisinger C, Thorand B (University of Ulm Medical Center, Ulm; German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg; and Institute for Clinical Diabetology, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany). Myeloperoxidase is associated with incident coronary heart disease independently of traditional risk factors: results from the MONICA/KORA Augsburg study. J Intern Med 2012; 271 : 43–50. Aims. Oxidative stress plays a critical role in the initiation and progression of atherosclerosis. Myeloperoxidase (MPO) is a marker of oxidative stress. We prospectively investigated whether an increased serum concentration of MPO is associated with an increased risk of incident coronary heart disease (CHD). Methods. We conducted a population‐based case‐cohort study in middle‐aged, healthy men and women within the MONICA/KORA Augsburg studies. Serum levels of MPO were measured in 333 subjects with (cases) and 1727 without (noncases) incident CHD. Mean follow‐up time was 10.8 ± 4.6 years. Results. Baseline concentrations of MPO were higher in cases compared with noncases (P ≤ 0.001 in men; P = 0.131 in women). After adjustment for major cardiovascular risk factors, the hazard ratio (HR) with 95% confidence interval (CI) comparing the top with the two lower tertiles was 1.70 (95% CI, 1.25–2.30). After additional adjustment for markers of inflammation and endothelial dysfunction, the association was attenuated (HR 1.50; 95% CI, 1.08–2.09). There were no significant interactions of MPO with sex or increased weight on CHD risk. Conclusions. Elevated concentrations of the oxidative stress marker MPO were independently associated with increased risk of incident CHD. This finding deserves detailed evaluation in further studies.     

C-reactive protein in the prediction of cardiovascular and overall mortality in middle-aged men: a population-based cohort study

Aims Cut-offs for C-reactive protein concentrations have beenrecommended for risk stratification, but little is known abouthow these cut-offs predict cardiovascular risk in population-basedcohorts. We therefore assessed the association of C-reactiveprotein levels with cardiovascular mortality in a population-basedcohort of 2321 middle-aged men stratified by the presence ofcardiovascular disease (CVD) at baseline. Methods and results C-reactive protein concentrations were categorizedaccording to current recommendations (1 and 3 mg/L). Duringthe 15 year follow-up, 77 men without CVD and 121 men with CVDat baseline died of CVD. In men without CVD at baseline (n=1476),age-adjusted cardiovascular mortality was 4.1-fold higher (95%CI 2.1–8.2) for C-reactive protein levels between 3.0and 9.9 mg/L at baseline than for C-reactive protein levels<1.0 mg/L. In men with CVD at baseline (n=845), thecorresponding age-adjusted cardiovascular mortality was 3.3-foldhigher (95% CI 2.0–5.3). Adjustment for conventional CVDrisk factors attenuated the risk somewhat. Further adjustmentfor dietary and lifestyle factors and factors related to insulinresistance did not affect the association. Classification ofC-reactive protein by tertiles gave qualitatively similar results,but identified twice as many men at high risk. C-reactive proteinlevels also predicted overall mortality. Conclusion Currently, recommended cut-offs for C-reactive proteinlevels identify men at risk for cardiovascular and overall deathindependently of conventional and other risk factors in a population-basedsample of middle-aged men with and without CVD at baseline.Lower cut-offs may better identify men at high risk for cardiovasculardeath, but improvement of current recommendations will requirestandardization of C-reactive protein assays.     

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: The MONICA/KORA Augsburg cohort study

Background and Aim

It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function.

Methods and Results

We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n = 833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n = 36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n = 21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models.Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. −4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively).

Conclusions

Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes.     

Chronic kidney disease and risk of incident myocardial infarction and all-cause and cardiovascular disease mortality in middle-aged men and women from the general population.

AIMS: Chronic kidney disease (CKD) was found to be an independent risk factor for all-cause mortality as well as adverse cardiovascular disease (CVD) events in high-risk populations. Findings from population-based studies are scarce and inconsistent. We investigated the gender-specific association of CKD with all-cause mortality, cardiovascular mortality, and incident myocardial infarction (MI) in a population-based cohort. METHODS AND RESULTS: The study was based on 3860 men and 3674 women (aged 45-74 years) who participated in one of the three MONICA Augsburg surveys between 1984 and 1995. CKD was defined by an estimated glomerular filtration rate between 15 and 59 mL/min/1.73 m(2). Hazard ratios (HRs) were estimated from Cox proportional hazard models. In this study, 890 total deaths, 400 CVD deaths, and 321 incident MIs occurred in men up to 31 December 2002; the corresponding numbers in women were 442, 187, and 102. In multivariable analyses, the HR for women with CKD compared to women with preserved renal function was significant for incident MI [HR 1.67; 95% confidence interval (CI) 1.07-2.61] and CVD mortality (HR 1.60; 95% CI 1.17-2.18). In men, CKD was also significantly associated with incident MI (HR 1.51; 95% CI 1.09-2.10) and CVD mortality (HR 1.48; 95% CI 1.15-1.92) after adjustment for common CVD risk factors. In contrast, men and women with CKD had no significant increased risk of all-cause mortality. CONCLUSION: CKD was strongly associated with an increased risk of incident MI and CVD mortality independent from common cardiovascular risk factors in men and women from the general population.     

C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg cohort study, 1984-1998

BACKGROUND: Previous studies have suggested that low-grade systemic inflammation is involved in the pathogenesis of type 2 diabetes mellitus. OBJECTIVE: To investigate the association between C-reactive protein (CRP), the classic acute-phase protein, and incident type 2 diabetes mellitus among middle-aged men. METHODS: A total of 2052 initially nondiabetic men aged 45 to 74 years who participated in 1 of the 3 MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg surveys between 1984 and 1995 were followed up for an average of 7.2 years. Incidence of diabetes was assessed by questionnaire mailed to participants in 1998. High-sensitive CRP was measured by an immunoradiometric assay. RESULTS: A total of 101 cases of incident diabetes occurred during the follow-up period. The age-standardized incidence rate was 6.9 per 1000 person-years. Men with CRP levels in the highest quartile (CRP > or = 2.91 mg/L) had a 2.7 times higher risk of developing diabetes (95% confidence interval, 1.4-5.2) compared with men in the lowest quartile (CRP < or = 0.67 mg/L) in a Cox proportional hazards model adjusted for age and survey. After further adjustment for body mass index, smoking, and systolic blood pressure, the observed association was significantly reduced and became nonsignificant. CONCLUSIONS: Low-grade systemic inflammation is associated with an increased risk of type 2 diabetes mellitus in middle-aged men. Inflammation could be one mechanism by which known risk factors for diabetes mellitus, such as obesity, smoking, and hypertension, promote the development of diabetes mellitus.     

Selected nutrient intakes of middle-aged men in southern Germany: results from the WHO MONICA Augsburg Dietary Survey of 1984/85.

In the WHO MONICA Augsburg survey of 1984/85 dietary intake was assessed in an age-stratified cluster sample of 899 men aged 45-64 years by 7-day records. The mean energy intake was 2,609 kcal (10.9 MJ), 15.9% of which came from protein, 38.1% from fat, and 36.6% from carbohydrate. A remarkably high proportion of 9.4% was derived from alcohol. Saturated fatty acids accounted for 14.6% of total energy, monounsaturated fatty acids for 13.2% and polyunsaturated fatty acids for 5.2%. The results showed that current dietary habits do not conform with the national nutritional guidelines.     

Characteristics and outcome of patients with acute myocardial infarction according to presenting electrocardiogram (from the MONICA/KORA Augsburg Myocardial Infarction--Registry)

Acute myocardial infarctions (AMIs) are categorized according to presenting electrocardiography into ST-elevation (STE), non-STE, and bundle branch block AMIs. Data on the characteristics and risks of these categories originate mainly from voluntary registries or clinical trials and may be hampered by selection and information bias. This study evaluated these different categories, with the additional differentiation of non-STE AMIs into ST-depression (STD) AMIs and those with nonspecific electrocardiographic signs (no-ST) in an unselected cohort. From 1985 to 2004, all consecutive patients aged 25 to 74 years who were hospitalized with AMI at the study region's major clinic were registered prospectively. A total of 6,748 patients were identified, of whom 45.8% had STE, 14.0% STD, 32.4% no-ST, and 7.8% bundle branch block AMIs, respectively. There were substantial differences in medical history, presentation, and therapy among the AMI types. Even after adjusting for the latter factors, the odds ratios of 28-day case fatality compared with no-ST were 1.26 (95% confidence interval 1.01 to 1.59) for STE, 1.84 (95% confidence interval 1.39 to 2.44) for STD, and 3.18 (95% confidence interval 2.37 to 4.27) for bundle branch block. In conclusion, after considering in-hospital therapy, the difference between STE and no-ST was nonsignificant, whereas the case-fatality difference between no-ST and STD persisted, suggesting some other unknown underlying factors associated with STD.     

Association of coronary heart disease with serum lipid and apolipoprotein concentrations in long-term diabetes. Results of the erfurt study

Summary The Erfurt study is concerned with the follow-up of all the 208 long-term diabetics out of the closed area of the Erfurt district with an at least 20 years’ diabetes survival in 1970. In 1980 risk factors for coronary heart disease (CHD) were assessed in 71 (85% type I diabetes) out of 76 patients still alive. Progression of CHD within the subsequent five years (death due to CHD in 8 cases and progression of the ECG findings according to the Minnesota code in 3 cases) was associated with older age, lower body mass index, higher triglycerides, and a higher total cholesterol/HDL cholesterol ratio in comparison with the surviving patients without progression (n=41). No significant differences could be found with regard to sex distribution, age at diabetes onset, duration of diabetes, percentage of type I diabetes, systolic and diastolic blood pressure, smoking behavior, prevalence of nephropathy, glycemic control, and serum levels of total cholesterol, LDL cholesterol, and HDL cholesterol. The subsequent reinvestigation in 1985 also included the determination of apolipoproteins. Since type II diabetes was not equally distributed, only type I diabetics were considered for the comparison of patients with ECG findings suggestive of CHD (n=5) with the remaining subjects (n=35). In addition to the above mentioned differences, CHD in long-term type I diabetes was also accompanied by lower HDL cholesterol, lower apolipoprotein A-I, and a higher apolipoprotein B/apolipoprotein A-I ratio. Substantially similar differences could be observed when type II diabetics were not excluded (10 patients with and 37 patients without CHD). It is concluded that the lipoprotein pattern is important for the survival in long-term diabetes.     

Myeloperoxidase, but not oxidized LDL, is associated with leisure-time physical activity: results from the MONICA/KORA Augsburg Studies 1984-1995

Objective

Oxidative stress-induced cell damage contributes to several chronic conditions such as cardiovascular disease, but only very few population-based studies have examined the influence of regular physical activity (PA) on oxidative stress.

Methods

1820 men and women aged 35–74 years were randomly drawn from three population-based MONICA/KORA Augsburg Studies conducted between 1984 and 1995. Geometric means of the oxidative stress markers myeloperoxidase (MPO) and oxidized LDL (ox-LDL) were calculated and multiple linear regression was performed to assess their associations with three self-reported PA domains, namely work, leisure-time or walking.

Results

Mean MPO concentrations were lower for participants engaged in high leisure-time PA (124.2 μg/ml; 95%-CI, 116.8–132.0) compared to the inactive reference group (133.5 μg/ml; 95%-CI, 127.6–139.6) (P_trend across PA levels: 0.007). No significant association between ox-LDL and PA domains was observed (P_trend between 0.162 and 0.803).

Conclusion

These data indicate that regular leisure-time PA may reduce MPO concentrations.     

Food intake and nutrient sources in the diet of middle-aged men in southern Germany: results from the WHO MONICA Augsburg Dietary Survey 1984/85.

Diet records of the WHO MONICA Augsburg dietary survey 1984/85 sample of 899 men aged 45-64 were used to derive quantitative data about food intake and the contribution of food groups to energy intake and the intake of those nutrients relevant to the discussion about nutrition and cardiovascular disease: protein, fat, saturated, mono- and polyunsaturated fatty acids, cholesterol, carbohydrate, polysaccharides and total fiber. The present lists of nutrient sources should be helpful for the development of acceptable dietary advises, which make allowance for actual eating patterns as well as for developing improved instruments of dietary assessment.     

Prognostic value of extensive coronary calcium quantities in symptomatic males--a 5-year follow-up study.

AIMS: Coronary calcium scores (CSs) have been shown to predict future events in patients presenting for first-time evaluation of CAD. Long-term outcome data on symptomatic subjects with advanced CAD are limited. In this study, we evaluated the prognostic value of very high coronary CSs in symptomatic males undergoing angiography and analyzed the impact of event definitions on identification of risk predictor's. METHODS AND RESULTS: Fifty consecutive symptomatic males with electron beam computed tomography (EBT)-based CSs >1000 were matched 1:2 by age with symptomatic males with scores between 400-1000 and 100-400. All 150 patients underwent coronary angiography. CAD risk factors were ascertained. Events were analyzed after 5 years for: (1) hard coronary events (coronary death and myocardial infarction); (2) overall hard events (adding stroke and non-coronary deaths); and (3) all events (including long-term revascularizations). During follow-up, 17 deaths, two infarctions and three strokes occurred in 21 patients; 38 patients underwent 43 revascularizations. Events occurred earlier and more frequently in patients with scores >1000. Left main disease was the only independent predictor of hard coronary events (hazard ratio, 4.5; 95% confidence interval, 1.1-17.8). Left main disease (4.3; 1.4-13.0) and CSs (1.7; 1.1-2.5) independently predicted overall hard events. Only CSs>90th percentile independently predicted all events (2.5; 1.3-4.8). CONCLUSIONS: Symptomatic males with extensive CSs carry an even higher risk for future events than other symptomatic males with advanced CAD. In these patients, EBT-based calcified plaque burden and angiographic indices of disease severity may have a complementary role in predicting future cardiovascular events.     

Implications of persistent prehypertension for ageing-related changes in left ventricular geometry and function: the MONICA/KORA Augsburg study

BACKGROUND: It is unclear whether persistent prehypertension causes structural or functional alterations of the heart. METHODS: We examined echocardiographic data of 1005 adults from a population-based survey at baseline in 1994/1995 and at follow-up in 2004/2005. We compared individuals who had either persistently normal (<120 mmHg systolic and <80 mmHg diastolic, n = 142) or prehypertensive blood pressure (120-139 mmHg or 80-89 mmHg, n = 119) at both examinations using multivariate regression modeling. RESULTS: Over 10 years, left ventricular end-diastolic diameters were stable and did not differ between the two groups. However, the prehypertensive blood pressure group displayed more pronounced ageing-related increases of left ventricular wall thickness (+4.7 versus +11.9%, P < 0.001) and left ventricular mass (+8.6 versus +15.7%, P = 0.006). Prehypertension was associated with a raised incidence of left ventricular concentric remodeling (adjusted odds ratio 10.7, 95% confidence interval 2.82-40.4) and left ventricular hypertrophy (adjusted odds ratio 5.33, 1.58-17.9). The ratio of early and late diastolic peak transmitral flow velocities (E/A) decreased by 7.7% in the normal blood pressure versus 15.7% in the prehypertensive blood pressure group (P = 0.003) and at follow-up the ratio of early diastolic peak transmitral flow and early diastolic peak myocardial relaxation velocities (E/EM) was higher (9.1 versus 8.5, P = 0.031) and left atrial size was larger (36.5 versus 35.3 mm, P = 0.024) in the prehypertensive blood pressure group. Finally, the adjusted odds ratio for incident diastolic dysfunction was 2.52 (1.01-6.31) for the prehypertensive blood pressure group. CONCLUSIONS: Persistent prehypertension accelerates the development of hypertrophy and diastolic dysfunction of the heart.