S. Möhlenkamp

Baseline recruitment and analyses of nonresponse of the Heinz Nixdorf Recall Study: identifiability of phone numbers as the major determinant of response.

The Heinz Nixdorf Recall Study is an ongoing population-based prospective cardiovascular cohort study of the Ruhr area in Germany. This paper focuses on the recruitment strategy and its response results including a comparison of participants of the baseline examination with nonparticipants. Random samples of the general population were drawn from residents’ registration offices including men and women aged 45–74 years. We used a multi-mode contact approach including an invitational letter, a maximum of two reminder letters and phone calls for the recruitment of study subjects. Nonparticipants were asked to fill in a short questionnaire. We calculated proportions of response, contact, cooperation and recruitment efficacy to characterize the participation. Overall, 4487 eligible subjects participated in our study. Although the elderly (65–75 years) had the highest contact proportion, the cooperation proportion was the lowest among both men and women. The recruitment efficacy proportion was highest among subjects aged 55–64 years. The identifiability of the phone number of study subjects was an important determinant of response. The recruitment efficacy proportion among subjects without an identified phone number was 11.4% as compared to 65.3% among subjects with an identified phone number. The majority of subjects agreed to participate after one invitational letter only (52.6%). A second reminding letter contributed only very few participants to the study. Nonparticipants were more often current smokers than participants and less often belonged to the highest social class. Living in a regular relationship with a partner was more often reported among participants than nonparticipants.

Cardiovascular Risk Factors in Patients with Uncontrolled and Long-Term Acromegaly: Comparison with Matched Data from the General Population and the Effect of Disease Control

CONTEXT Data on cardiovascular risk in acromegaly are scanty and lack a clear correlation to epidemiological data. OBJECTIVE Our aim was an evaluation of cardiovascular risk factors in patients with active acromegaly, a calculation of the Framingham risk score (FRS) compared with age- and gender-matched controls of the general population, and an evaluation of the effect of IGF-I normalization. DESIGN AND SETTING We conducted a retrospective, comparative study at a university referral center. PATIENTS A total of 133 patients with acromegaly (65 men, aged 45-74 yr) from the German Pegvisomant Observational Study were matched to 665 controls from the general population. MAIN OUTCOME MEASURES Risk factors were measured at baseline and after 12 months of treatment with pegvisomant (n=62). RESULTS Patients with acromegaly had increased prevalence of hypertension, mean systolic and diastolic blood pressure (BP), history of diabetes mellitus and glycosylated hemoglobin (all P<0.001) and decreased high-density lipoprotein, low-density lipoprotein, and total cholesterol (all P<0.001). FRS was significantly higher in patients with acromegaly compared with controls (P<0.001). At 12 months, systolic BP (P=0.04) and glycosylated hemoglobin (P=0.02) as well as FRS (P=0.005) decreased significantly. IGF-I was normalized in 62% (41 of 62). In these patients, glucose and systolic and diastolic BP was significantly lower than in partially controlled patients. SUMMARY We found an increased prevalence of cardiovascular risk factors in acromegalic patients compared with controls. Control of acromegaly led to a significant decrease of FRS, implying a reduced risk for coronary heart disease. This was most significant in those patients who completely normalized their IGF-I levels. CONCLUSION Disease control is important to reduce the likelihood for development of coronary heart disease.

Low socio-economic position is associated with poor social networks and social support: results from the Heinz Nixdorf Recall Study

BackgroundSocial networks and social support are supposed to contribute to the development of unequal health within populations. However, little is known about their socio-economic distribution. In this study, we explore this distribution.MethodsThis study analyses the association of two indicators of socio-economic position, education and income, with different measures of social networks and support. Cross-sectional data have been derived from the baseline examination of an epidemiological cohort study of 4.814 middle aged urban inhabitants in Germany (Heinz Nixdorf Recall Study). Bivariate and multivariate logistic regression analysis were carried out to estimate the risk of having poor social networks and support across socio-economic groups.ResultsSocially disadvantaged persons more often report poor social networks and social support. In multivariate analyses, based on education, odds ratios range from 1.0 (highest education) to 4.9 (lowest education) in a graded way. Findings based on income show similar effects, ranging from 1.0 to 2.5. There is one exception: no association of SEP with close ties living nearby and regularly seen was observed.ConclusionPoor social networks and low social support are more frequent among socio-economically disadvantaged people. To some extent, this finding varies according to the indicator chosen to measure these social constructs.

Coronary atherosclerosis and cardiovascular risk in masters male marathon runners : Rationale and design of the marathon study

Background:Regular physical exercise is recommended to reduce cardiovascular mortality. And yet, atherosclerosis is the main cause of exercise-associated death in persons beyond age 35. The need for risk stratification in marathon runners is under discussion. The predictive value of modern imaging- and non-imaging-based markers of risk that can be used for risk stratification in masters endurance athletes still deserves exploration.Methods:Male runners > 50 years who have completed at least five marathon races during the preceding 3 years and do not suffer from coronary artery disease, angina nor diabetes mellitus are studied to assess the predictive value of established and modern imaging- based and biochemical cardiovascular risk factors. Laboratory parameters including clinical chemistry, hematology and hormone measurements are determined. Lifestyle-related risk factors, psychosocial and socioeconomic variables are explored using standardized questionnaires. Coronary, carotid, femoral and aortic atherosclerosis is measured using electronbeam computed tomography and ultrasound. In addition, a resting ECG, a bicycle stress test and heart rate variability are performed. Myocardial morphology and function are assessed using echocardiography and magnetic resonance imaging. Participants are invited to compete in a marathon race to quantify the association of coronary atherosclerosis with marathon-related changes of cardiac troponin levels and the extent of marathon-induced inflammation. At the cellular level, the effect on the amount of circulating progenitor cells (EPCs) is determined by FACS analysis. Changes in laboratory parameters and hormone levels are also studied. Annual long-term follow-up including hospital records and death certificates is performed. Data are compared with those from a general unselected cohort from the Heinz Nixdorf Recall Study.Conclusion:This study should contribute to cardiovascular risk assessment in the growing number of masters marathon runners with a focus on assessing the predictive value of modern imaging techniques and biochemical markers for comprehensive risk stratification.ZusammenfassungHintergrund:Regelmäßige körperliche Aktivität eignet sich zur Prävention der Arteriosklerose und kardiovaskulärer Ereignisse. Und dennoch ist die Arteriosklerose die Hauptursache sportassoziierter Todesfälle jenseits des 35. Lebensjahrs. Der prädiktive Nutzen moderner bildgebender Verfahren und biochemischer Marker, die für eine Risikostratifizierung in Frage kommen, wurde bei älteren Ausdauersportlern bislang nicht hinreichend untersucht.Methodik:Es werden Männer > 50 Jahre untersucht, die in den vergangenen 3 Jahren mindestens fünf Marathonläufe absolviert haben und keine bekannte Herzkrankheit oder Angina pectoris und keinen Diabetes mellitus aufweisen. Etablierte Risikofaktoren sowie moderne bildgebende und biochemische Risikomarker werden gemessen. Lebensstilassoziierte, psychosoziale und sozioökonomische Risikofaktoren werden mit standardisierten Fragebögen erhoben. Die Arteriosklerose der Koronararterien, der Karotiden, der Femoralarterien und der Aorta wird mittels Elektronenstrahltomographie und Ultraschall quantifiziert. Zusätzlich werden ein Ruhe-EKG, eine Fahrradergometrie und eine Messung der Herzfrequenzvariabilität durchgeführt. Morphologie und Funktion des linken Ventrikels werden echokardiographisch und magnetresonanztomographisch erfasst. Die Teilnehmer wurden gebeten, an einem Marathonwettkampf teilzunehmen, um die Assoziation von Koronarsklerose und dem marathoninduzierten Anstieg von kardialem Troponin in Abhängigkeit von der erwarteten Entzündungsreaktion zu untersuchen. Auf zellulärer Ebene wird der Effekt auf die Anzahl zirkulierender endothelialer Vorläuferzellen (EPCs) mittels FACS-Analyse bestimmt. Die Ereignisrate im Verlauf wird jährlich erfragt. Es werden auch Krankenhausdokumente und Sterbeunterlagen ausgewertet. Die Daten können im Vergleich zur Allgemeinbevölkerung aus der Heinz-Nixdorf-Recall-Studie analysiert werden.Schlussfolgerung:Diese Studie kann einen Beitrag zur kardiovaskulären Risikostratifikation in der wachsenden Gruppe älterer Marathonläufer leisten. Der prädiktive Wert der bildgebenden und biochemischen Marker für kardiovaskuläre Ereignisse wird untersucht.

Poor social relations and adverse health behaviour: stronger associations in low socioeconomic groups?

ObjectivePoor social relations are supposed to contribute to adverse health behaviour. We examined this association and the role of low socio-economic position.MethodsWe regressed health behaviour on composite variables of the two exposures of social relations and socio-economic position (SEP). Social relations included networks and support; health behaviour was analysed in terms of smoking, poor nutrition and physical inactivity; socio-economic position comprised of income and education. Cross sectional data from a population based epidemiological study in German (4,814 men and women aged 45–75) was analysed.ResultsAmong the indicators for social relations, social isolation was consistently associated with adverse health behaviour; social support showed modest effect. A combination of poor social relations and low SEP displayed stronger (additive) associations with adverse health behaviour than each factor alone. However, superadditivity was excluded.ConclusionGiven the important role of health adverse behaviour in chronic disease development, results underline the relevance of social environment and socio-economic structure in Public Health interventions.

Prognostic value of electron-beam computed tomography-derived coronary calcium scores compared with clinical parameters in patients evaluated for coronary artery disease: Prognostic value of EBCT in symptomatic patients

Das mittels Elektronenstrahltomographie (EBT) nichtinvasiv gemessene Ausmaß der Koronarsklerose ist als wichtiger prognostischer Faktor bei symptomatischen Patienten beschrieben worden. Die isolierte Analyse der EBT-Befunde lässt jedoch keine klinisch sinnvolle Aussage über den möglichen Stellenwert der Methode zu, und klinische Tests wie Risikofaktorenanalyse, Belastungs-EKG und Koronarangiographie liefern ihrerseits wichtige prognostische Information. Wir kontaktierten 300 Patienten, die wegen KHK-verdächtiger Symptomatik untersucht worden waren und alle auch ein EBT erhielten, 3,5 Jahre später. Komplette Follow-Up Information war für 255 (85%) verfügbar (Eingangsalter 58±11 Jahre, 71% Männer). Es wurden 4 klinische Risikokategorien unterschieden: (1) ≤1 kausaler Risikofaktor, (2) Ischämienachweis im Belastungstest oder ≥2 Risikofaktoren, (3) angiographisch nach-gewiesene KHK, (4) Koronarintervention/Operation im Rahmen der Erstabklärung. Follow-Up Ereignisse wurden bei 40 Patienten beobachtet: Progression der KHK (PTCA/Stent/OP) (n = 35), Myokardinfarkt (n = 2), Herztod (n = 3) (insgesamt bezeichnet als MACE, major adverse cardiac events). Die 4 klinischen Kategorien waren hochsignifikante Prädiktoren von MACE. Das relative Risiko stieg von 1 in Gruppe (1) auf 1,5 in (2), 6,8 in (3) und 28,3 in (4). In univariater Analyse bedeutete ein EBT-Kalkscore >100 (n = 105) ein relatives Risiko von 12,0 (95% CI, 4,7–30,6). Nach Adjustierung für den EBT-Kalkscore und für das Alter lag das relative Risiko der klinischen Kategorien in (2) bei 1,3, in (3) bei 3,6 und in (4) bei 12,0. Das adjustierte relative Risiko eines EBT-Kalkscore >100 betrug 4,4 (95% CI, 1,5–12,6). Die gängigen klinischen Parameter erlauben eine prognostische Einschätzung von symptomatischen Patienten. Die EBT-Untersuchung der Koronarsklerose ist ein davon unabhängiger prognostischer Faktor und verbessert die prognostische Einschätzung. The electron-beam computed tomography-(EBCT-)derived calcium score provides a measure of coronary atherosclerotic plaque disease which may allow for more precise risk stratification in symptomatic patients. However, it remains unclear if EBCT can add prognostic information compared with the clinical information derived from risk factor assessment, exercise stress testing, and coronary angiography. A cohort of 300 consecutive patients with recent (<3 months) onset of symptoms was retrospectively identified who were examined for possible coronary artery disease (CAD) and who all underwent EBCT. Successful follow-up after 3.5 years was obtained in 255 (85%) patients whose mean age at baseline was 58±11 years (n = 181 (71%), males). Four clinical categories with increasing evidence of CAD were constructed on the basis of risk factor assessment, exercise stress testing, coronary angiographic anatomy, and coronary revascularization at baseline. During follow-up, major adverse cardiac events (MACE: myocardial infarction, cardiac death, revascularization) were observed in 40 (16%) patients, including myocardial infarction and cardiac death in 5 patients. The 4 clinical categories were highly predictive of MACE, with a relative risk estimate of 28.3 (95% CI, 6.7–119.1) in the upper vs. the reference category. In univariate analysis, the relative risk estimate of MACE associated with a calcium score ≥100 was 12.0 (95% CI, 4.7–30.6). After adjustment for the clinical categories and for age, this estimate decreased in multivariate analysis, but remained predictive at 4.4 (95% CI, 1.5–12.6). In patients with first-time evaluation of possible CAD, EBCT-derived coronary calcium is suggested to provide for independent and additional information compared with the clinically available information.

B-type natriuretic peptide predicts stroke of presumable cardioembolic origin in addition to coronary artery calcification

B‐type natriuretric peptide (BNP) is a marker of cardiac dysfunction that is released from myocytes in response to ventricular wall stress. Previous studies suggested that BNP predicts stroke events in addition to classical risk factors. It was suggested that the BNP‐associated risk results from coronary atherosclerosis or atrial fibrillation.

Prognostic value of electron-beam computed tomography-derived coronary calcium scores compared with clinical parameters in patients evaluated for coronary artery disease

Das mittels Elektronenstrahltomographie (EBT) nichtinvasiv gemessene Ausmaß der Koronarsklerose ist als wichtiger prognostischer Faktor bei symptomatischen Patienten beschrieben worden. Die isolierte Analyse der EBT-Befunde lässt jedoch keine klinisch sinnvolle Aussage über den möglichen Stellenwert der Methode zu, und klinische Tests wie Risikofaktorenanalyse, Belastungs-EKG und Koronarangiographie liefern ihrerseits wichtige prognostische Information. Wir kontaktierten 300 Patienten, die wegen KHK-verdächtiger Symptomatik untersucht worden waren und alle auch ein EBT erhielten, 3,5 Jahre später. Komplette Follow-Up Information war für 255 (85%) verfügbar (Eingangsalter 58±11 Jahre, 71% Männer). Es wurden 4 klinische Risikokategorien unterschieden: (1) ≤1 kausaler Risikofaktor, (2) Ischämienachweis im Belastungstest oder ≥2 Risikofaktoren, (3) angiographisch nach-gewiesene KHK, (4) Koronarintervention/Operation im Rahmen der Erstabklärung. Follow-Up Ereignisse wurden bei 40 Patienten beobachtet: Progression der KHK (PTCA/Stent/OP) (n = 35), Myokardinfarkt (n = 2), Herztod (n = 3) (insgesamt bezeichnet als MACE, major adverse cardiac events). Die 4 klinischen Kategorien waren hochsignifikante Prädiktoren von MACE. Das relative Risiko stieg von 1 in Gruppe (1) auf 1,5 in (2), 6,8 in (3) und 28,3 in (4). In univariater Analyse bedeutete ein EBT-Kalkscore >100 (n = 105) ein relatives Risiko von 12,0 (95% CI, 4,7–30,6). Nach Adjustierung für den EBT-Kalkscore und für das Alter lag das relative Risiko der klinischen Kategorien in (2) bei 1,3, in (3) bei 3,6 und in (4) bei 12,0. Das adjustierte relative Risiko eines EBT-Kalkscore >100 betrug 4,4 (95% CI, 1,5–12,6). Die gängigen klinischen Parameter erlauben eine prognostische Einschätzung von symptomatischen Patienten. Die EBT-Untersuchung der Koronarsklerose ist ein davon unabhängiger prognostischer Faktor und verbessert die prognostische Einschätzung. The electron-beam computed tomography-(EBCT-)derived calcium score provides a measure of coronary atherosclerotic plaque disease which may allow for more precise risk stratification in symptomatic patients. However, it remains unclear if EBCT can add prognostic information compared with the clinical information derived from risk factor assessment, exercise stress testing, and coronary angiography. A cohort of 300 consecutive patients with recent (<3 months) onset of symptoms was retrospectively identified who were examined for possible coronary artery disease (CAD) and who all underwent EBCT. Successful follow-up after 3.5 years was obtained in 255 (85%) patients whose mean age at baseline was 58±11 years (n = 181 (71%), males). Four clinical categories with increasing evidence of CAD were constructed on the basis of risk factor assessment, exercise stress testing, coronary angiographic anatomy, and coronary revascularization at baseline. During follow-up, major adverse cardiac events (MACE: myocardial infarction, cardiac death, revascularization) were observed in 40 (16%) patients, including myocardial infarction and cardiac death in 5 patients. The 4 clinical categories were highly predictive of MACE, with a relative risk estimate of 28.3 (95% CI, 6.7–119.1) in the upper vs. the reference category. In univariate analysis, the relative risk estimate of MACE associated with a calcium score ≥100 was 12.0 (95% CI, 4.7–30.6). After adjustment for the clinical categories and for age, this estimate decreased in multivariate analysis, but remained predictive at 4.4 (95% CI, 1.5–12.6). In patients with first-time evaluation of possible CAD, EBCT-derived coronary calcium is suggested to provide for independent and additional information compared with the clinically available information.

Cardiac risk in patients with treatment naïve, first-line medically controlled and first-line surgically cured acromegaly in comparison to matched data from the general population.

INTRODUCTION Coronary risk factors in patients with acromegaly after first-line transsphenoidal surgery (TSS) or first-line somatostatine analogue (SSA) treatment have rarely been examined. Aim of this study was an evaluation of cardiovascular risk factors and left ventricular hypertrophy (LVH) in 3 different patient groups with treatment naïve, active (ACT), first-line medically controlled (MED) and first-line surgically treated (SUR) acromegaly and a calculation of the Framingham Weibull Risk Score (FS). DESIGN Retrospective comparative matched case-control study. PATIENTS & METHODS 40 acromegalic patients (cases aged 45-74 years, 23 men) were matched with respect to age and gender to 200 controls from the general population. 13 patients had treatment-naïve acromegaly (ACT), 12 patients were SSA treated (MED) and 15 patients were operated by TSS (SUR). Coronary risk factors were assessed after 12 months of treatment by interviews and direct laboratory measurements. Only patients normalized for IGF-I in MED and SUR group were included. FS and odds ratios (OR) from multiple conditional logistic regression (matched for age and gender, adjusted for BMI) were calculated. RESULTS Compared to matched controls ACT patients had higher HbA1c levels (6.9±1.4 vs. 5.5±0.7% (p<0.0001)) and an increased prevalence of left ventricular hypertrophy (LVH) (30.8 vs. 3.2% (p=0.007). MED and SUR groups were similar for gender, age, disease duration and IGF-I levels at diagnosis. Compared to matched controls, MED patients had a significantly increased diastolic blood pressure (89±9 vs. 79±11 mmHg (p=0.001), prevalence of LVH (41.7 vs. 1.7% (p<0.0001), prevalence of diabetes mellitus (33.3 vs. 10.0% (p=0.03)), higher HbA1c levels (6.8±1.3 vs. 5.5±0.7% (p=0.0005)) and a higher FS (21.2±9.7 vs. 12.4±7.7% (p=0.002), OR 1.11 [1.02-1.21] (p=0.01)) while in the SUR group only higher prevalences of LVH (40.0 vs. 4.1% (p<0.0001)) and HbA1c levels (6.4±1.2 vs. 5.5±0.8% (p=0.006)) were found compared to controls. CONCLUSION When comparing treatment naive, medically treated and surgically cured patients with acromegaly to age- and gender-matched subjects from the general population, we have found an increased cardiovascular risk in patients at 12 months after first-line SSA treatment but not in patients after first-line surgery.

Comparison of dual-source and electron-beam CT for the assessment of coronary artery calcium scoring.

OBJECTIVE Cardiac CT allows the detection and quantification of coronary artery calcification (CAC). Electron-beam CT (EBCT) has been widely replaced by high-end CT generations in the assessment of CAC. The aim of this study was to compare the CAC scores derived from an EBCT with those from a dual-source CT (DSCT). METHODS We retrospectively selected 92 patients (61 males; mean age, 60.7 ± 12 years) from our database, who underwent both EBCT and DSCT. CAC was assessed using the Agatston score by two independent readers (replicates: 1, 2; 3=mean of reading 1 and 2). RESULTS EBCT scores were on average slightly higher than DSCT scores (281 ± 569 vs 241 ± 502; p<0.05). In regression analysis R(2)-values vary from 0.956 (1) to 0.966 (3). We calculated a correction factor as EBCT=(DSCT+1)(1.026)-1. When stratifying into CAC categories (0, 1-99, 100-399, 400-999 and ≥1000), 79 (86%) were correctly classified. From those with positive CAC scores, 7 out of 61 cases (11%, κ=0.81) were classified in different categories. Using the corrected DSCT CAC score, linear regression analysis for the comparison to the EBCT results were r=0.971 (p<0.001), with a mean difference of 6.4 ± 147.8. Five subjects (5.4%) were still classified in different categories (κ=0.84). CONCLUSION CAC obtained from DSCT is highly correlated with the EBCT measures. Using the calculated correction factor, agreement only marginally improved the clinical interpretation of results. Overall, for clinical purposes, face value use of DSCT-derived values appears as useful as EBCT for CAC scoring.