Cardiovascular profiling in the diabetic continuum: results from the population-based Gutenberg Health Study.

AIMS: To assess the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in the general population and to investigate the associated cardiovascular burden and clinical outcome. METHODS AND RESULTS: The study sample comprised 15,010 individuals aged 35-74 years of the population-based Gutenberg Health Study. Subjects were classified into euglycaemia, prediabetes and T2DM according to clinical and metabolic (HbA1c) information. The prevalence of prediabetes was 9.5% (n = 1415) and of T2DM 8.9% (n = 1316). Prediabetes and T2DM showed a significantly increased prevalence ratio (PR) for age, obesity, active smoking, dyslipidemia, and arterial hypertension compared to euglycaemia (for all, P < 0.0001). In a robust Poisson regression analysis, prediabetes was established as an independent predictor of clinically-prevalent cardiovascular disease (PRprediabetes 1.20, 95% CI 1.07-1.35, P = 0.002) and represented as a risk factor for asymptomatic cardiovascular organ damage independent of traditional risk factors (PR 1.04, 95% CI 1.01-1.08, P = 0.025). Prediabetes was associated with a 1.5-fold increased 10-year risk for cardiovascular disease compared to euglycaemia. In Cox regression analysis, prediabetes (HR 2.10, 95% CI 1.76-2.51, P < 0.0001) and T2DM (HR 4.28, 95% CI 3.73-4.92, P < 0.0001) indicated for an increased risk of death. After adjustment for age, sex and traditional cardiovascular risk factors, only T2DM (HR 1.89, 95% CI 1.63-2.20, P < 0.0001) remained independently associated with increased all-cause mortality. CONCLUSION: Besides T2DM, also prediabetes inherits a significant cardiovascular burden, which translates into poor clinical outcome and indicates the need for new concepts regarding the prevention of cardiometabolic disorders.

Right atrium size in the general population.

Echocardiography is the most common routine cardiac imaging method. Nevertheless, only few data about sex-specific reference limits for right atrium (RA) dimensions are available. Transthoracic echocardiographic RA measurements were studied in 9511 participants of the Gutenberg-Health-Study. A reference sample of 1942 cardiovascular healthy subjects without chronic obstructive pulmonary disease was defined. We assessed RA dimensions and sex-specific reference limits were defined using the 95th percentile of the reference sample. Results showed sex-specific differences with larger RA dimensions in men that were attenuated by standardization for body-height. RA-volume was 20.2 ml/m in women (5th-95th: 12.7-30.4 ml/m) and 26.1 ml/m in men (5th-95th: 16.0-40.5 ml/m). Multivariable regressions identified body-mass-index (BMI), coronary artery disease (CAD), chronic heart failure (CHF) and atrial fibrillation (AF) as independent key correlates of RA-volume in both sexes. All-cause mortality after median follow-up-period of 10.7 (9.81/11.6) years was higher in individuals who had RA volume/height outside the 95% reference limit (HR 1.70 [95%CI 1.29-2.23], P = 0.00014)). Based on a large community-based sample, we present sex-specific reference-values for RA dimensions normalized for height. RA-volume varies with BMI, CHF, CAD and AF in both sexes. Individuals with RA-volume outside the reference limit had a 1.7-fold higher mortality than those within reference limits.

Chronic venous insufficiency, cardiovascular disease, and mortality: a population study.

AIMS: Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce. METHODS AND RESULTS: Systematic phenotyping of CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40-80 years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was done in an independent cohort study (MyoVasc, NCT04064450). The prevalence of telangiectasia/reticular, varicose veins, and CVI was 36.5% [95% confidence interval (CI), 35.6-37.4%], 13.3% [12.6-13.9%], and 40.8% [39.9-41.7%], respectively. Age, female sex, arterial hypertension, obesity, smoking, and clinically overt cardiovascular disease were identified as clinical determinants of CVI. Higher CEAP classes were associated with a higher predicted 10-year risk for incident cardiovascular disease in individuals free of cardiovascular disease (n = 9923). During a mean follow-up of 6.4 ± 1.6 years, CVI was a strong predictor of all-cause death independent of the concomitant clinical profile and medication [hazard ratio (HR) 1.46 (95% CI 1.19-1.79), P = 0. 0003]. The association of CVI with an increased risk of all-cause death was externally validated in the MyoVasc cohort [HR 1.51 (95% CI 1.11-2.05), P = 0.009]. CONCLUSION: Chronic venous insufficiency is highly prevalent in the population and is associated with the presence of cardiovascular risk factors and disease. Individuals with CVI experience an elevated risk of death, which is independent of age and sex, and present cardiovascular risk factors and comorbidities.

What's past is prologue: Recalled parenting styles are associated with childhood cancer survivors' mental health outcomes more than 25 years after diagnosis.

BACKGROUND: With the increased survival rates of childhood cancer, long-term survivors' well-being over the life span has come into focus. A better understanding of the determinants of childhood cancer survivors' (CCS) mental health outcomes contributes to the identification of vulnerable individuals as well as to the development of evidence-based prevention and intervention efforts. It has been noted that psychosocial factors such as parental rearing behavior shape individual differences in mental health. There is also evidence that parents show altered parenting behavior in the face of childhood cancer, e. g. that they express more emotional support, but also more worries. However, little is known about the relevance of different parenting styles for CCS' mental health decades after diagnosis and treatment. METHODS: We examined the associations of recalled parenting styles and disease-related factors with lifetime diagnoses of depression and anxiety disorders in a German, registry-based sample of adult CCS (N = 948, 44.50% women) with survival times >25 years. We conducted logistic regression analyses of lifetime diagnoses of depression and anxiety disorders, respectively, on dimensions of recalled parental rearing behavior (measured with a validated German short version of the EMBU) controlling for relevant adjustment variables such as the presence of physical illnesses. RESULTS: Recalled parenting styles of both parents had statistically relevant associations with CCS' lifetime depression and anxiety diagnoses. Maternal emotional warmth was related to fewer lifetime diagnoses of depression and fewer lifetime diagnoses of anxiety. Memories of paternal control and overprotection were positively associated with lifetime diagnoses of anxiety. CONCLUSION: The results indicate that mental representations of one's caregivers are associated with psychological long-term outcomes. Thus, medical professionals should involve the parents and support them in accompanying their child through the difficult times of treatment and survivorship. Interventions aimed at fostering survivors' quality of life should consider the sustained relevance of early relationships.

Risk factors for suicidal ideation in a large, registry-based sample of adult long-term childhood cancer survivors.

INTRODUCTION: Long-term childhood cancer survivors (CCS) are at risk for physical and psychosocial late effects. Previous research has attested to increased rates of suicidal ideation (SI) in CCS, an especially dangerous indicator of distress. However, little was known about risk factors of SI among CCS which go beyond illness- and treatment related variables. METHODS: A registry-based sample of 916 adult long-term CCS (Mage=34.58 years [SD=5.53], Mage at diagnosis=6.15 years [SD=4.28]) underwent medical assessments and filled out questionnaires. We conducted a linear regression analysis on SI, testing predictors of different areas: sociodemographic, social, physical health and health behavior, and psychological distress symptoms. RESULTS: SI was reported by 73 (8.0%) CCS and previous suicide attempts were reported by 26 (2.8%) CCS. SI was most closely related to social and psychological factors, i.e. to concurrent distress symptoms (depression, anxiety, social phobia), previous suicide attempts, current loneliness, and the present living situation. LIMITATIONS: SI and previous suicide attempts were assessed using short self-report instruments. The cross-sectional study design does not allow for causal inferences. CONCLUSIONS: Long-term CCS are a previously understudied, vulnerable group. Decades after having survived cancer, a considerable percentage is affected by (recurrent) SI. CCS' risk for SI is likely shaped by individual medical and psychological history, and by the current social environment and psychological comorbidities. There is a need for more interdisciplinary research and for screening efforts which take account of these factors. Interventions reducing CCS' risk of suicide should foster social integration and counteract current stressors.

Status and predictors of planning ability in adult long-term survivors of CNS tumors and other types of childhood cancer.

Long-term childhood cancer survivors' (CCS) quality of life can be impacted by late effects such as cognitive difficulties. Especially survivors of CNS tumors are assumed to be at risk, but reports of cognitive tests in CCS with survival times >25 years are scarce. We assessed planning ability, a capacity closely related to fluid intelligence, using the Tower of London. We compared 122 CNS tumor survivors, 829 survivors of other cancers (drawn from a register-based sample of adult long-term CCS), and 215 healthy controls (using sex-specific one-way ANOVAs and t-tests). Associations of CCS' planning ability with medical and psychosocial factors were investigated with a hierarchical linear regression analysis. Mean planning ability did not differ between CCS and controls. However, female CNS tumor survivors performed worse than female survivors of other cancers and female controls. CNS tumor survivors of both sexes had a lower socioeconomic status, and fewer of them had achieved high education than other survivors. In the regression analysis, lower status and anxiety symptoms were associated with poor planning, suggesting possible mediators of effects of disease and treatment. The results indicate the necessity to contextualize test results, and to include cognitive and psychological assessments into aftercare.

Parenting in the face of serious illness: Childhood cancer survivors remember different rearing behavior than the general population.

OBJECTIVE: A child's cancer diagnosis and treatment affect the whole family. While it has been recognized that parents are an important resource for their children, little is known about the specifics of parenting in the face of serious illness. METHODS: We used the Recalled Parental Rearing Behavior Questionnaire in a register-based cohort of adult childhood cancer survivors (CCS) (N = 951) and a representative population sample of the same age range (N = 2042). The questionnaire assesses behavior of mothers and fathers with three scales (emotional warmth, rejection/punishment, and control/overprotection) by querying the (former) child. We compared the two groups using general linear models. With a hierarchical linear regression analysis, we tested associations of recalled rearing behavior with disease- and treatment-related factors. RESULTS: Compared with the general population, CCS remembered both parents as emotionally warmer, more overprotective, and less punishing/rejecting and less ambitious. The regression analysis showed that having received radiotherapy (ß = 0.092; P = .009) and chemotherapy (ß = 0.077; P = .027) was positively related to memories of maternal emotional warmth. CONCLUSIONS: CCS remembered parenting styles which are generally deemed more positive. The extent of recalled control and overprotection deviated from the population in different directions, suggesting that parenting in childhood cancer entails more complex adaptations than being affectionate and giving comfort. The results suggest an adaptation of parental behavior to particularly challenging treatments. They highlight potential vulnerability and resilience factors, some of which were sex-dependent.

Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study.

BACKGROUND: Elevated levels of FVIII: c are associated with risk for both venous and arterial thromboembolism. However, no population-based study on the sex-specific distribution and reference ranges of plasma FVIII: c and its cardiovascular determinants is available. FVIII: c was analyzed in a randomly selected sample of 2533 males and 2440 females from the Gutenberg Health Study in Germany. Multivariable regression analyses for FVIII: c were performed under adjustment for genetic determinants, cardiovascular risk factors and cardiovascular disease. RESULTS AND CONCLUSIONS: Females (126.6% (95% CI: 125.2/128)) showed higher FVIII: c levels than males (121.2% (119.8/122.7)). FVIII: c levels increased with age in both sexes (ß per decade: 5.67% (4.22/7.13) male, 6.15% (4.72/7.57) female; p<0.001). Sex-specific reference limits and categories indicating the grade of deviation from the reference were calculated, and nomograms for FVIII: c were created. FVIII: c was approximately 25% higher in individuals with non-O blood type. Adjusted for sex and age, ABO-blood group accounted for 18.3% of FVIII: c variation. In multivariable analysis, FVIII: c was notably positively associated with diabetes mellitus, obesity, hypertension and dyslipidemia and negatively with current smoking. In a fully adjusted multivariable model, the strongest associations observed were of elevated FVIII: c with diabetes and peripheral artery disease in both sexes and with obesity in males. Effects of SNPs in the vWF, STAB2 and SCARA5 gene were stronger in females than in males. The use of nomograms for valuation of FVIII: c might be useful to identify high-risk cohorts for thromboembolism. Additionally, the prospective evaluation of FVIII: c as a risk predictor becomes feasible.

Cryoballoon versus RF ablation in paroxysmal atrial fibrillation: results from the German Ablation Registry.

BACKGROUND: Catheter ablation is used extensively with curative intention in atrial fibrillation. Radiofrequency ablation has long been a standard of care, while cryoballoon technology has emerged as a feasible approach with promising results. Prospective multicenter registry data referring to both ablation technologies in AF ablation therapy are lacking. METHODS: Between January 2007 and August 2011, a total of 3,775 consecutive patients with symptomatic paroxysmal AF who underwent PV ablation in their respective centers were enrolled. The cohort was divided into 2 groups according to the ablation energy source used: cryoballoon ablation (group 1, n = 905 [24.0%], median age 63 years, 64.3% men) and RF ablation (group 2, n = 2870 [76.0%], median age 63 years, 62.7% men). Comorbidities and baseline clinical characteristics were similar in both groups. RESULTS: Acute success rate was similar in both groups (97.5% in cryo vs 97.6% in RF; P = 0.81). Procedure times were similar, ablation and fluoroscopy times were higher in cryoballoon when compared to RF ablation. Overall complication rate was similar in cryo- (4.6%) and RF-ablation (4.6%; P = 1.0). Phrenic nerve palsy was more often in cryo versus RF ablation (2.1% in cryo vs 0.0% in RF; P < 0.001). Other complications were more common in RF compared to cryoablation (4.6% in RF vs 2.7% in cryo; P < 0.05). CONCLUSION: RF ablation is the most widespread ablation method in Germany, but use of cryoballoon increased significantly. Procedure times were similar, but ablation and fluoroscopy times were longer in cryoballoon ablation. No significant differences were found in terms of acute success and overall complication rate.

Effects of a secondary prevention combination therapy with an aspirin, an ACE inhibitor and a statin on 1-year mortality of patients with acute myocardial infarction treated with a beta-blocker. Support for a polypill approach.

OBJECTIVE: Large randomized clinical trials have shown the efficacy of aspirin, ACE (angiotensin converting enzyme) inhibitors and statins as secondary prevention measures in patients after an acute coronary syndrome with and without ST elevations. Therefore we aimed to determine the effect of a combination therapy with these three drugs on 1-year mortality after acute myocardial infarction (AMI). METHODS: We prospectively followed 9998 survivors of acute myocardial infarction treated with a beta-blocker for 1 year. Patients were divided into three groups according to their therapy with aspirin, ACE inhibitors and statins: 3 drugs, 2 drugs or 0-1 drug. RESULTS: The majority of patients (n = 6260, 62.6%) were treated with 3 drugs, 2986 (29.9%) with 2 drugs and 752 (7.5%) with 0-1 drug. In the univariate analysis 1-year mortality was 4.9%, 9.7% and 13.6%, respectively. After adjusting for confounding factors in the propensity score analysis the odds ratios for 1-year mortality were significantly increased with 0-1 drug (odds ratio 1.67, 95% CI 1.24-2.27) and with 2 drugs (odds ratio 1.54, 95% CI 1.26-1.87) in comparison with the group treated with all 3 drugs. However, in the ACOS registry the treatment was left to the discretion of the physician. This could lead to a selection bias, which cannot be fully eliminated by using multiple regression analysis. CONCLUSIONS: A combination therapy with aspirin, an ACE inhibitor and a statin reduces 1-year mortality in patients after AMI. Therefore a polypill approach with these three agents should be considered to increase drug compliance and reduce mortality after acute myocardial infarction.

Effect of an invasive strategy on in-hospital outcome and one-year mortality in women with non-ST-elevation myocardial infarction.

BACKGROUND: Subgroup analyses from randomized studies show inconsistent results regarding an early invasive approach in women with non-ST-elevation myocardial infarction (NSTEMI). We sought to investigate the impact of an invasive strategy in clinical practice, analyzing data from the German Acute Coronary Syndromes registry (ACOS). METHODS: Overall 1986 consecutive women were enrolled in the registry between June 2000 and November 2002 and were divided into two groups: 1215 (61.2%) underwent coronary angiography, 771 (38.8%) received conservative treatment. In the invasive group percutaneous coronary intervention was performed in 40.7% within 48 h and in 16.4% after 48 h, whereas 8.3% underwent coronary artery bypass grafting within hospital stay. RESULTS: In-hospital death (3.2% vs 10.5%, p<0.0001), in-hospital death/myocardial infarction (MI) (7.1% vs 14.9%, p<0.0001) and one-year death (8.1% vs 24%) occurred significantly less often in patients with invasive strategy. After adjustment of the confounding factors in the propensity score analysis the invasive strategy showed no significant benefit for in-hospital death (OR 0.86, 95% CI 0.51-1.44) or death/MI (OR 0.70, 95% CI 0.47-1.04) but remained superior for mortality (OR 0.47, 95% CI 0.3-0.7) and death/MI one year after discharge (OR 0.47, 95% CI 0.33-0.68). CONCLUSIONS: In clinical practice women presenting with NSTEMI have a long-term benefit from an invasive therapeutic strategy with a significant reduction in mortality as well as the composite endpoint of death/MI.

Prevalence and overlap of different lipid abnormalities in statin-treated patients at high cardiovascular risk in clinical practice in Germany.

BACKGROUND: In line with current guideline recommendations, patients at high cardiovascular risk are usually treated with statins for secondary as well as for primary prevention. While many studies investigated treatment goal achievement with regards to low-density lipoprotein (LDL-C) and total cholesterol (TC) there is paucity of data regarding high density lipoprotein (HDL-C), and/or triglycerides (TG). SETTING: Prospective, cross-sectional study (Dyslipidemia International Survey, DYSIS) with data provided by 748 office-based physicians throughout Germany. METHODS: Consecutive patients were eligible for participation, if they were at least 45 years old, currently treated with a statin and had had a documented lipid profile (at least 1 parameter) within the last 6 months. Besides descriptive analyses, logistic regression was performed with backward selection to assess predictors for lipid abnormalities (non-attainment of goals for TC, LDL-C, low HDL-C or elevated TG) classified according to current European Society of Cardiology guidelines. RESULTS: The 4,282 documented patients (98.6% Caucasian, 56.4% male; 86.6% at high cardiovascular risk) were predominantly treated with simvastatin (83.9%), pravastatin (7.7%) or atorvastatin (3.9%), usually with doses equivalent to simvastatin 20-40 mg daily. Non-statins were used in at most 12% of patients. No lipid abnormalities were found in 21.0% of patients, one abnormality in 38.5%, two in 31.9%, and all three in 8.5%. LDL-C goals were not attained in 58.1%, elevated TC was found in 66.6%, low HDL-C in 22.7%, and elevated TG in 47.3%. In the multivariate logistic regression model, non-attainment of LDL-C levels was predicted by hypertension (odds ratio, OR 1.4), current smoking (OR 1.3), sedentary lifestyle (OR 1.3), and female gender (OR 1.3). On the other hand, a reduced risk for missing LDL-C targets was noted in the presence of ischemic heart disease (OR 0.6), diabetes (0.5), higher statin doses, ezetimibe treatment, or specialist care, respectively. CONCLUSION: A substantial proportion of statin-treated patients not only missed targets for LDL-C, but also did not attain the normal levels for HDL-C and/or TG. There is a large disconnect between high prevalence of HDL and/or TG disorders, with or without elevated LDL-C, and utilization of therapies targeting these lipids. Particularly in high-risk patients, additional efforts should be made to improve their lipid profile.

Effect of an invasive strategy on in-hospital outcome in elderly patients with non-ST-elevation myocardial infarction.

AIMS: We sought to investigate the impact of an invasive treatment in elderly patients presenting with non-ST elevation myocardial infarction (NSTEMI) in clinical practice. METHODS AND RESULTS: We analysed data of consecutive elderly patients (> or =75 years) with NSTEMI who were prospectively enrolled in the German Acute Coronary Syndromes registry between July 2000 and November 2002. Overall 1936 patients were divided into two groups: 1005 (51.9%) underwent coronary angiography and/or revascularization, 931 (48.1%) received conservative treatment. In the invasive group, percutaneous coronary intervention was performed in 37.5% within 48 h and in 17.6% after 48 h, whereas 9.8% underwent coronary artery bypass grafting within the hospital stay. In-hospital death (12.5 vs. 6.0%, P < 0.0001) and death/myocardial infarction (17.3 vs. 9.6%, P < 0.0001) occurred significantly less often in patients with invasive strategy. After adjustment of the confounding factors in the propensity score analysis the invasive strategy remained superior for mortality (OR 0.55, 95% CI 0.35-0.86) and death and non-fatal myocardial infarction (OR 0.51, 95% CI 0.35-0.75) and 1 year mortality (OR 0.56, 95% CI 0.38-0.81). Major bleeding complications tended to be more frequent in the invasive group (8.8 vs. 5.8%, P = 0.07). CONCLUSION: In clinical practice, in elderly patients with NSTEMI, an invasive strategy is associated with an improved in-hospital and 1 year outcome but a trend towards more bleeding complications.

Relative role of NT-pro BNP and cardiac troponin T at 96 hours for estimation of infarct size and left ventricular function after acute myocardial infarction.

BACKGROUND: N-terminal brain-type natriuretic peptide (NT-pro BNP) and cardiac troponin T (cTnT) after acute myocardial infarction (AMI) have proven useful for prediction of prognosis and may be valuable for assessment of left ventricular function and infarct size. The aim of the present study was to correlate infarct size and left ventricular function determined by cine and late gadolinium enhanced CMR with plasma levels of TNT and NT-pro BNP levels after AMI. METHODS: We studied 44 patients (pts) with first ST- and non-ST-segment elevation myocardial infarction (STEMI=23 pts.,NSTEMI=21 pts.). We measured NT-pro BNP and cTnT on a single occasion at 96 hours after onset of symptoms. RESULTS: There was a moderate inverse correlation between NT-pro BNP and LV-EF in STEMI (r=-0.67, p=0.0009) and NSTEMI (r=-0.85, p<0.0001). Likewise, cTnT showed a significant inverse correlation with LV-EF in STEMI (r=-0.54, p=0.014) but not in NSTEMI. With cTnT there was a strong linear correlation with infarct mass and relative infarct size in STEMI (r=0.92, p<0.0001) and NSTEMI (r=0.59, p<0.0093). NT-pro BNP demonstrated a good relationship with infarct mass (r=0.79, p<0.0001) and relative infarct size (r=0.75, p<0.0001) in STEMI, but not in NSTEMI. CONCLUSION: A single NT-pro BNP and cTnT value at 96 hours after onset of symptoms proved useful for estimation of LV-EF and infarct size. In direct comparison, NT-pro BNP disclosed a better performance for estimation of LV-EF whereas cTnT was superior for assessment of infarct mass and relative infarct size, suggesting an implementation of a dual marker strategy for diagnostic and prognostic work-up.