Lars Pieper

The Predictive Value of Different Measures of Obesity for Incident Cardiovascular Events and Mortality

CONTEXT To date, it is unclear which measure of obesity is the most appropriate for risk stratification. OBJECTIVE The aim of the study was to compare the associations of various measures of obesity with incident cardiovascular events and mortality. DESIGN AND SETTING We analyzed two German cohort studies, the DETECT study and SHIP, including primary care and general population. PARTICIPANTS A total of 6355 (mean follow-up, 3.3 yr) and 4297 (mean follow-up, 8.5 yr) individuals participated in DETECT and SHIP, respectively. INTERVENTIONS We measured body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) and assessed cardiovascular and all-cause mortality and the composite endpoint of incident stroke, myocardial infarction, or cardiovascular death. RESULTS In both studies, we found a positive association of the composite endpoint with WHtR but not with BMI. There was no heterogeneity among studies. The relative risks in the highest versus the lowest sex- and age-specific quartile of WHtR, WC, WHR, and BMI after adjustment for multiple confounders were as follows in the pooled data: cardiovascular mortality, 2.75 (95% confidence interval, 1.31-5.77), 1.74 (0.84-3.6), 1.71 (0.91-3.22), and 0.74 (0.35-1.57), respectively; all-cause mortality, 1.86 (1.25-2.76), 1.62 (1.22-2.38), 1.36 (0.93-1.69), and 0.77 (0.53-1.13), respectively; and composite endpoint, 2.16 (1.39-3.35), 1.59 (1.04-2.44), 1.49 (1.07-2.07), and 0.57 (0.37-0.89), respectively. Separate analyses of sex and age groups yielded comparable results. Receiver operating characteristics analysis yielded the highest areas under the curve for WHtR for predicting these endpoints. CONCLUSIONS WHtR represents the best predictor of cardiovascular risk and mortality, followed by WC and WHR. Our results discourage the use of the BMI.

Type 2 diabetes mellitus and medications for type 2 diabetes mellitus are associated with risk for and mortality from cancer in a German primary care cohort.

There is growing evidence that patients with type 2 diabetes mellitus have increased cancer risk. We examined the association between diabetes, cancer, and cancer-related mortality and hypothesized that insulin sensitizers lower cancer-related mortality. Participants in the Diabetes Cardiovascular Risk and Evaluation: Targets and Essential Data for Commitment of Treatment study, a nationwide cross-sectional and prospective epidemiological study, were recruited from German primary care practices. In the cross-sectional study, subjects with type 2 diabetes mellitus had a higher prevalence of malignancies (66/1308, 5.1%) compared to nondiabetic subjects (185/6211, 3.0%) (odds ratio, 1.64; 95% confidence interval, 1.12-2.41) before and after adjustment for age, sex, hemoglobin A(1c), smoking status, and body mass index. Patients on metformin had a lower prevalence of malignancies, comparable with that among nondiabetic patients, whereas those on any other oral combination treatment had a 2-fold higher risk for malignancies even after adjusting for possible confounders; inclusion of metformin in these regimens decreased the prevalence of malignancies. In the prospective analyses, diabetic patients in general and diabetic patients treated with insulin (either as monotherapy or in combination with other treatments) had a 2- and 4-fold, respectively, higher mortality rate than nondiabetic patients, even after adjustment for potential confounders (incidence of cancer deaths in patients with type 2 diabetes mellitus [2.6%] vs the incidence of cancer deaths in patients without type 2 diabetes mellitus [1.2%]). Our results suggest that diabetes and medications for diabetes, with the exception of the insulin sensitizer metformin, increase cancer risk and mortality.

Diabetes in Primary Care: Prospective Associations between Depression, Nonadherence and Glycemic Control

Background: Findings are inconsistent regarding the degree to which depression may exert a negative impact on glycemic control in patients with type 2 diabetes. We therefore aimed to examine the longitudinal relationship between depression, behavioral factors, and glycemic control. Methods: In a prospective component of a nationally representative sample, 866 patients with type 2 diabetes aged ≧18 years completed a standardized assessment including a laboratory screening, questionnaires, and diagnostic measures. Subsequent to baseline (t₀), patients were tracked over a period of 12 months (t1). Depression was assessed according to DSM-IV and ICD-10 criteria. Glycemic control was determined by levels of glycosylated hemoglobin (HbA1c); a level of ≧7% was judged as unsatisfactory. Regression analyses were performed to analyze the prospective relationship between depression, medication adherence, diabetes-related health behavior, and HbA1c. Results: Patients with depression at t₀ revealed increased rates of medication nonadherence (adjusted OR: 2.67; CI: 1.38–5.15) at t1. Depression (adjusted regression coefficient: β = 0.96; p = 0.001) and subthreshold depression (β = 1.01; p < 0.001) at t₀ also predicted increased problems with diabetes-related health behavior at t1. Adjusted ORs for poor glycemic control (HbA1c ≧7%) at t1 were also increased for patients with baseline depression (2.01; CI: 1.10–3.69). However, problems with medication adherence as well as problems with diabetes-related health behavior at t₀ did not predict poor glycemic control at t1. Conclusions: In a prospective representative study of patients with type 2 diabetes, baseline depression predicted problems with medication adherence, problems with health-related behaviors, and unsatisfactory glycemic control at follow-up.

General Practitioners Recognizing Alcohol Dependence: A Large Cross-Sectional Study in 6 European Countries

PURPOSE Although alcohol dependence causes marked mortality and disease burden in Europe, the treatment rate is low. Primary care could play a key role in reducing alcohol-attributable harm by screening, brief interventions, and initiating or referral to treatment. This study investigates identification of alcohol dependence in European primary care settings. METHODS Assessments from 13,003 general practitioners, and 9,098 interviews (8,476 joint number of interviewed patients with a physician’s assessment) were collected in 6 European countries. Alcohol dependence, comorbidities, and health service utilization were assessed by the general practitioner and independently using the Composite International Diagnostic Interview (CIDI) and other structured interviews. Weighted regression analyses were used to compare the impact of influencing variables on both types of diagnoses. RESULTS The rate of patients being identified as alcohol dependent by the CIDI or a general practitioner was about equally high, but there was not a lot of overlap between cases identified. Alcohol-dependent patients identified by a physician were older, had higher rates of physicial comorbidity (liver disease, hypertension), and were socially more marginalized, whereas average consumption of alcohol and mental comorbidity were equally high in both groups. CONCLUSION General practitioners were able to identify alcohol dependence, but the cases they identified differed from cases identified using the CIDI. The role of the CIDI as the reference standard should be reexamined, as older alcohol-dependent patients with severe comorbidities seemed to be missed in this assessment.

Low testosterone levels predict all-cause mortality and cardiovascular events in women: a prospective cohort study in German primary care patients

OBJECTIVE Although associations between testosterone and cardiovascular (CV) morbidity in women have been proposed, no large prospective study has evaluated potential associations between testosterone and mortality in women. The objective was to determine whether baseline testosterone levels in women are associated with future overall or CV morbidity and mortality. DESIGN Prospective cohort study with a 4.5-year follow-up period. METHODS From a representative sample of German primary care practices, 2914 female patients between 18 and 75 years were analyzed for the main outcome measures: CV risk factors, CV diseases, and all-cause mortality. RESULTS At baseline, the study population was aged 57.96±14.37 years with a mean body mass index of 26.71±5.17 kg/m(2). No predictive value of total testosterone for incident CV risk factors or CV diseases was observed in logistic regressions. Patients with total testosterone levels in the lowest quintile Q1, however, had a higher risk to die of any cause or to develop a CV event within the follow-up period compared to patients in the collapsed quintiles Q2-Q5 in crude and adjusted Cox regression models (all-cause mortality: Q2-Q5 versus Q1: crude hazard ratios (HR) 0.49, 95% confidence interval (CI) 0.33-0.74; adjusted HR 0.62, 95% CI 0.42-0.939; CV events: Q2-Q5 versus Q1: crude HR 0.54, 95% CI 0.38-0.77; adjusted HR 0.68, 95% CI 0.48-0.97). Kaplan-Meier curves revealed similar data. CONCLUSIONS Low baseline testosterone in women is associated with increased all-cause mortality and incident CV events independent of traditional risk factors.

Diabetes Mellitus in German Primary Care: Quality of Glycaemic Control and Subpopulations not well Controlled - Results of the DETECT Study

INTRODUCTION The quality of glycaemic control of patients with T1D and T2D can be assessed with HbA (1c) levels. We aimed to assess the quality of glycaemic control and the prevalence of inadequately controlled diabetes in German primary care, and to determine simple patient and treatment related factors associated with poor control. MATERIAL AND METHODS Using a nationwide probability sample of 3 188 general practices (response rate 50.6%), a total of 55,518 patients were assessed in DETECT, a cross-sectional and prospective multistage epidemiological study. Diabetes diagnoses were based on physician assessment. HbA (1c) values were taken from the patient charts. RESULTS The quality of metabolic control was unsatisfactory on the whole in the 277 people with T1D (e.g. mean HbA (1c)=7.4%+/-1.4%). The 8 188 people with T2D had a mean HbA (1c) of 6.89%+/-1.2%. 38.8% of individuals had an HbA (1c)>/=7.0%. The situation was less favourable in subjects with a longer history of diabetes - in many cases in those with diabetes for 5-9 years, but generally in those with a plus-10-year history of diabetes - and also in younger men with a shorter disease history. Patients with a short T2D history, especially older subjects had more favourable values. With regard to age, a higher percentage of patients had an HbA (1c)>/=7.0% (42.0% and 40.6%) in the 45-54 and 55-64 year olds. With respect to the correlation between HbA (1c) and treatment modality, we identified the best metabolic control in T2D patients without drug therapy for diabetes, and the worst in patients on combination regimens (OAD/insulin). The average duration of diabetes in the various treatment groups differs substantially. The average duration was highest (12.1 y) in the insulin group. Oral treatment was the predominant treatment modality in all HbA (1c) categories. CONCLUSION T1D treatment needs to be improved overall. The situation as regards T2D is less clear-cut. When people with T2D start requiring more intensive and complex treatment in response to disease progression, the treatment efforts of patients and physicians evidently fail to keep up with the actual pace of metabolic deterioration. Early and strict alignment with approximately normal HbA (1c) targets is essential. Close attention should be paid to T2 diabetics with a 5-9-year diabetes history, with the aim of preventing any loss of metabolic control. Likewise, patients aged 45-64 y and younger men require more attention.

Inadequate medical treatment of patients with coronary artery disease by primary care physicians in Germany

SummaryAimsThe DETECT study was performed to obtain representative data about the frequency, distribution, and treatment of patients with coronary artery disease (CAD) in the primary care setting in Germany.Methods and resultsThe DETECT study was a cross–sectional clinical– epidemiological survey of a nationally representative sample of 3795 primary care offices and 55 518 patients. Overall, 12.4% of patients were diagnosed with CAD. Stable angina pectoris and myocardial infarction were the most frequent (4.2%) subgroups, followed by status post (s/p) percutaneous coronary interventions (PCI, 3.0%) and s/p coronary bypass surgery (2.2%). Patients with CAD were prescribed AT1 receptor antagonists (in 19.4% of cases), beta blockers (57.2%), ACE inhibitors (49.9%), antiplatelet agents (52.7%), statins (43.0%), and long–term nitrates (24.5%). When comparing all CAD patients with social health care insurance to those who had private insurance, private patients had significantly higher rates of revascularisation procedures and use of preventive medications.ConclusionGreat potential remains for improving secondary prevention in primary care in Germany to reduce the risk of further coronary or vascular events, especially in patients with social health care insurance.

Prediction of incident diabetes mellitus by baseline IGF1 levels

OBJECTIVE IGF1 is associated with metabolic parameters and involved in glucose metabolism. Low-IGF1 has been implicated in the etiology of glucose intolerance and subjects with pathological causes of either low- or high-IGF1 are at risk of diabetes. We hypothesized that both low- and high-IGF1 levels increase the risk of diabetes and aimed to assess the role of IGF1 in the risk of developing diabetes in a large prospective study. DESIGN An analysis of two prospective cohort studies, the DETECT study and SHIP. METHODS We measured IGF1 levels in 7777 nondiabetic subjects and assessed incident diabetes mellitus during follow-up. RESULTS There were 464 cases of incident diabetes during 32 229 person-years (time of follow-up in the DETECT study and SHIP: 4.5 and 5 years respectively). There was no heterogeneity between both studies (P > 0.4). The hazard ratios (HRs) of incident diabetes in subjects with IGF1 levels below the 10th or above the 90th age- and sex-specific percentile, compared to subjects with intermediate IGF1 levels, were 1.44 (95% confidence interval (CI) 1.07-1.94) and 1.55 (95% CI 1.06-2.06) respectively, after multiple adjustment. After further adjustment for metabolic parameters, the HR for low-IGF1 became insignificant. Analysis of IGF1 quintiles revealed a U-shaped association of IGF1 with risk of diabetes. Results remained similar after exclusion of patients with onset of new diabetes within 1 year or with borderline glucose or HbA1c levels at baseline. CONCLUSIONS Subjects with low- or high-IGF1 level are at increased risk of developing diabetes.

Changes in the prevalence, treatment and control of hypertension in Germany? A clinical-epidemiological study of 50.000 primary care patients.

Introduction Medical societies have developed guidelines for the detection, treatment and control of hypertension (HTN). Our analysis assessed the extent to which such guidelines were implemented in Germany in 2003 and 2001. Methods Using standardized clinical diagnostic and treatment appraisal forms, blood pressure levels and patient questionnaires for 55,518 participants from the cross-sectional Targets and Essential Data for Commitment of Treatment (DETECT) study (2003) were analyzed. Physician’s diagnosis of hypertension (HTNdoc) was defined as coding hypertension in the clinical appraisal questionnaire. Alternative definitions used were physician’s diagnosis or the patient’s self-reported diagnosis of hypertension (HTNdoc,pat), physician’s or patient’s self-reported diagnosis or a BP measurement with a systolic BP≥140 mmHg and/or a diastolic BP≥90 (HTNdoc,pat,bp) and diagnosis according to the National Health and Nutrition Examination Survey (HTNNHANES). The results were compared with the similar German HYDRA study to examine whether changes had occurred in diagnosis, treatment and adequate blood pressure control (BP below 140/90 mmHg) since 2001. Factors associated with pharmacotherapy and control were determined. Results The overall prevalence rate for hypertension was 35.5% according to HTNdoc and 56.0% according to NHANES criteria. Among those defined by NHANES criteria, treatment and control rates were 56.0% and 20.3% in 2003, and these rates had improved from 55.3% and 18.0% in 2001. Significant predictors of receiving antihypertensive medication were: increasing age, female sex, obesity, previous myocardial infarction and the prevalence of comorbid conditions such as coronary heart disease (CHD), hyperlipidemia and diabetes mellitus (DM). Significant positive predictors of adequate blood pressure control were CHD and antihypertensive medication. Inadequate control was associated with increasing age, male sex and obesity. Conclusions Rates of treated and controlled hypertension according to NHANES criteria in DETECT remained low between 2001 and 2003, although there was some minor improvement.

Circulating Troponin As Measured by a Sensitive Assay for Cardiovascular Risk Assessment in Primary Prevention

BACKGROUND Measuring circulating cardiac troponin using novel sensitive assays has revealed that even minute elevations are associated with increased mortality in patients with coronary artery disease or even in the general population. Less well defined, however, is the incremental value of measuring circulating cardiac troponin I (cTnI) by a sensitive assay for risk assessment in primary prevention. METHODS We measured circulating concentrations of cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) in 5388 individuals free of known cardiovascular disease recruited into the DETECT study, a prospective longitudinal population-based cohort study. We determined the prognostic implications for incident major adverse cardiovascular events (MACE) during 5 years of follow-up. RESULTS Circulating cTnI was detectable in 19% of the subjects. Increased cTnI concentrations were associated with established risk factors for atherosclerosis and demonstrated a graded relationship with all-cause mortality and incident MACE during 5-year follow-up. A single measurement of cTnI significantly improved risk prediction over established risk factors, and also added prognostic information, when adjusted for serum concentrations of NT-proBNP and hsCRP. CONCLUSIONS Minute increases in cTnI are associated with increased mortality and incident MACE in a large primary prevention cohort and, thus, identify contributors to cardiovascular risk not fully captured by traditional risk factor assessment.