Aggregation of type-2 diabetes, prediabetes, and metabolic syndrome in German couples.

We aimed to examine the concordance of type-2 diabetes, prediabetes and the metabolic syndrome in couples. In cross-sectional analyses, we used data from 1173 couples with index persons from the Heinz Nixdorf Recall Study (2011-2015), a population-based cohort study in Western Germany, and partners from the associated Heinz Nixdorf Multigeneration Study (2013-2016). Mean age (standard deviation) was 67.2 (6.6) years in index persons, and 67.8 (7.7) years in partners. The exposure was the presence of diabetes, prediabetes or metabolic syndrome in index persons, the outcome was the presence of the same health status in partners. Diabetes was defined by either self-reported diagnosis, intake of antidiabetic drugs or insulin, or HbA1c ≥ 6.5%. If the index person had prediabetes or diabetes, the partner was 1.46 (95% CI 1.07-2.00) times more likely to have diabetes than partners of index persons without the condition in the crude model (adjusted model: 1.33 (0.97-1.83)). For self-reported diabetes and for the metabolic syndrome, the corresponding prevalence ratios were 1.33 (0.90-1.97) and 1.17 (1.03-1.32), respectively (adjusted models: 1.23 (0.77-1.94), 1.04 (0.91-1.18)). In German couples, there was weak to moderate concordance of type-2 diabetes, prediabetes and the metabolic syndrome in crude, but poor concordance in adjusted models.

Early Postoperative Complications of One-Stage Substitution Urethroplasty with Oral Mucosa Graft: A Monocentric Retrospective Study.

INTRODUCTION: We report early postoperative complications (PCs) (≤90 days) of one-stage oral mucosa graft (OMG) urethroplasty in treatment of acquired anterior urethral strictures. MATERIAL AND METHODS: In this study, we evaluated 530 males who underwent one-stage substitution urethroplasty (SU) between September 1996 and October 2020. Medical records were reviewed to identify and classify early PCs based on the Clavien-Dindo classification (CDC). We subdivided the PCs into three groups with different kinds of complications which allowed us a more detailed analysis concerning general surgical complications (GSCs), donor site morbidity (DSM) and complications specific for free graft urethroplasty (CSUs). The influence of patient demographics, stricture characteristics and operative procedure on the occurrence of PCs was analysed. RESULTS: Early (90-day) PCs occurred in 90 (16.98%) patients, whereas only 19 patients (3.58%) experienced serious events (CDC grades III and IV). Early complications include 4.5% GSCs, 1.7% DSM and 10.8% CSUs. Only stricture length turned out to be an independent statistically significant risk factor for the occurrence of early PCs. There was a trend towards a higher rate of complications in patients with ASA III compared to ASA I. CONCLUSION: The incidence of severe early complications in patients undergoing one-stage SU with OMG is low.

Blood Kallikrein-8 and Non-Amnestic Mild Cognitive Impairment: An Exploratory Study.

Background: Blood kallikrein-8 is supposed to be a biomarker for mild cognitive impairment (MCI) due to Alzheimer's disease (AD), a precursor of AD dementia. Little is known about the association of kallikrein-8 and non-AD type dementias. Objective: To investigate whether blood kallikrein-8 is elevated in individuals with non-amnestic MCI (naMCI), which has a higher probability to progress to a non-AD type dementia, compared with cognitively unimpaired (CU) controls. Methods: We measured blood kallikrein-8 at ten-year follow-up (T2) in 75 cases and 75 controls matched for age and sex who were participants of the population-based Heinz Nixdorf Recall study (baseline: 2000-2003). Cognitive performance was assessed in a standardized manner at five (T1) and ten-year follow-up. Cases were CU or had subjective cognitive decline (SCD) at T1 and had naMCI at T2. Controls were CU at both follow-ups. The association between kallikrein-8 (per 500 pg/ml increase) and naMCI was estimated using conditional logistic regression: odds ratios (OR) and 95% confidence intervals (95% CI) were determined, adjusted for inter-assay variability and freezing duration. Results: Valid kallikrein-8 values were measured in 121 participants (45% cases, 54.5% women, 70.5±7.1 years). In cases, the mean kallikrein-8 was higher than in controls (922±797 pg/ml versus 884±782 pg/ml). Kallikrein-8 was not associated with having naMCI compared to being CU (adjusted; OR: 1.03 [95% CI: 0.80-1.32]). Conclusion: This is the first population-based study that shows that blood kallikrein-8 tends not to be elevated in individuals with naMCI compared with CU. This adds to the evidence of the possible AD specificity of kallikrein-8.

Cross-sectional analysis of pulsatile hemodynamics across the adult life span: reference values, healthy and early vascular aging: the Heinz Nixdorf Recall and the MultiGeneration Study.

BACKGROUND: Pulsatile hemodynamics predict major cardiovascular events. We aimed to provide comprehensive population-based reference values and to compare different measures of pulsatile hemodynamics to define early vascular aging (EVA) as well as healthy vascular aging (HVA). METHODS: In 2721 participants from the population-based Heinz Nixdorf Recall Study and the associated MultiGeneration Study, free from diabetes, cardiovascular disease, and antihypertensive drugs, we performed high-fidelity radial tonometry, calibrated waveforms with brachial blood pressures and processed them with a validated transfer function, pulse wave analysis, and wave separation analysis. Aortic pulse wave velocity (aoPWV) was estimated with a validated regression formula. HVA was defined as the lowest, EVA as the highest age-specific decile of central pulse pressure (cPP), backward wave amplitude, and aoPWV. RESULTS: Overall, 56.4% of participants were female, age range 18-90 years. Brachial PP increased from middle age, whereas cPP increased across the entire adult life span. Wave reflections increased across all age groups, apart from a plateau in older male participants. Indices of wave reflection were higher in women than in men. AoPWV showed the most prominent rise with age in both sexes. EVA and HVA, defined by cPP and backward wave amplitude, differed mainly by hemodynamic variables. In contrast, EVA participants were characterized by a worse hemodynamic, anthropometric, metabolic, and inflammatory profile, if aoPWV was used to discriminate EVA and HVA. CONCLUSION: Age-specific and sex-specific reference values for central pulsatile hemodynamics in a general white population cohort are provided and may be utilized to define HVA and EVA.

Experience with One-Stage Repair of Urethral Strictures Using the Augmented Anastomotic Repair Technique.

INTRODUCTION: We report the results of augmented anastomotic repair (AAR) in the treatment of anterior urethral strictures. MATERIAL AND METHODS: In this retrospective study, we evaluated 71 consecutive patients who had undergone AAR between June 2004 and June 2013. Medical records were reviewed to identify early postoperative complications based on the Clavien-Dindo classification (CDC). Self-developed standardized questionnaires sent to the patients and referring urologists were used to collect data on late complications (>90) days. Stricture recurrence (SR) was defined as any postoperative endoscopic or open surgical intervention on the urethra. The influence of patient demographics, stricture characteristics, and operative procedure performed on the occurrence of SR was analyzed. RESULTS: Early postoperative complications were rare events (11.3%) with only one severe CDC complication. Late complications were reported in 46.5% cases. At a median follow-up of 17 months (range 3-114 months), however, 64 patients had no evidence of SR and required no further intervention, giving an overall success rate of 90.1%. Seven patients with SR had a higher body mass index, were older, and had been operated on by less experienced surgeon(s). Most SRs occurred within the first year after surgery. CONCLUSIONS: AAR was an effective and safe operative technique that allowed one-stage repair in our patients with anterior urethral strictures who needed resection of the scarred urethra and otherwise were not suitable for primary anastomosis or simple substitution urethroplasty.

Value of Progression of Coronary Artery Calcification for Risk Prediction of Coronary and Cardiovascular Events: Result of the HNR Study (Heinz Nixdorf Recall).

BACKGROUND: Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events. METHODS: In 3281 participants (45-74 years of age), free from cardiovascular disease until the second visit, risk factors, and CTs at baseline (b) and after a mean of 5.1 years (5y) were measured. Hard coronary and cardiovascular events, and total cardiovascular events including revascularization, as well, were recorded during a follow-up time of 7.8±2.2 years after the second CT. The added predictive value of 10 CAC progression algorithms on top of risk factors including baseline CAC was evaluated by using survival analysis, C-statistics, net reclassification improvement, and integrated discrimination index. A subgroup analysis of risk in CAC categories was performed. RESULTS: We observed 85 (2.6%) hard coronary, 161 (4.9%) hard cardiovascular, and 241 (7.3%) total cardiovascular events. Absolute CAC progression was higher with versus without subsequent coronary events (median, 115 [Q1-Q3, 23-360] versus 8 [0-83], P<0.0001; similar for hard/total cardiovascular events). Some progression algorithms added to the predictive value of baseline CT and risk assessment in terms of C-statistic or integrated discrimination index, especially for total cardiovascular events. However, CAC progression did not improve models including CAC5y and 5-year risk factors. An excellent prognosis was found for 921 participants with double-zero CACb=CAC5y=0 (10-year coronary and hard/total cardiovascular risk: 1.4%, 2.0%, and 2.8%), which was for participants with incident CAC 1.8%, 3.8%, and 6.6%, respectively. When CACb progressed from 1 to 399 to CAC5y≥400, coronary and total cardiovascular risk were nearly 2-fold in comparison with subjects who remained below CAC5y=400. Participants with CACb≥400 had high rates of hard coronary and hard/total cardiovascular events (10-year risk: 12.0%, 13.5%, and 30.9%, respectively). CONCLUSIONS: CAC progression is associated with coronary and cardiovascular event rates, but adds only weakly to risk prediction. What counts is the most recent CAC value and risk factor assessment. Therefore, a repeat scan >5 years after the first scan may be of additional value, except when a double-zero CT scan is present or when the subjects are already at high risk.

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10-6; pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.

Accelerated progression of coronary artery calcification in hypertension but also prehypertension.

OBJECTIVE: To determine the role of hypertension for coronary artery calcification (CAC) progression. METHODS: The population-based Heinz Nixdorf Recall study recruited 4814 participants from a German urban population in 2000-2003. CAC was measured using electron-beam computed tomography at baseline and after 5 years. The present analyses refer to 3481 participants with repeat scan (coronary heart disease until 5 years excluded, age at baseline 45-74 years, and 53.1% women). Blood pressure (BP), Framingham risk factors, and antihypertensive medication were recorded at baseline. BP was staged according to Joint National Committee 7 guidelines. Participants under antihypertensive medication were classified as stage 2. CAC at 5 years was predicted from baseline using our dedicated, publicly available algorithm. CAC progression was accordingly classified as slow, expected, or rapid. RESULTS: Normotension was found in 20.5%, prehypertension in 27.2%, stage 1 hypertension in 15.8%, and stage 2 (ST2) in 36.5%. The frequency of rapid progression increases with BP stage (normotension: 16.7% to ST2: 21.1%, P = 0.004). Risk factor adjusted relative risk [RR (95% confidence interval), reference: normotension] of rapid progression was for prehypertension: 1.22 (0.98;1.51), stage 1: 1.29 (1.01;1.65), and ST2: 1.45 (1.17;1.79). Risk factor adjusted measures of CAC progression per 10 mmHg SBP were already elevated in women with BP below 140/90 mmHg: CAC onset, RR = 1.22 (1.07;1.40), rapid progression, RR = 1.17 (1.05;1.31), 5-year CAC progression, 6.7% (0.5;13.4). In men below 140/90 mmHg, only RR of rapid progression was considerably increased [RR = 1.11 (0.96;1.29)]. CONCLUSION: CAC progression, a sign of ongoing target organ damage, is already accelerated in prehypertensive patients, a substantial proportion of our urban population.

Noncoronary Measures Enhance the Predictive Value of Cardiac CT Above Traditional Risk Factors and CAC Score in the General Population.

OBJECTIVES: The aim of this study was to determine whether noncoronary measures from cardiac computed tomography (CT) may enhance the prognostic value of this imaging technology. BACKGROUND: When cardiac CT is performed for quantification of coronary artery calcium (CAC) score, information on other cardiac and thoracic structures is available. METHODS: Participants without known cardiovascular disease from the prospective population based Heinz Nixdorf Recall study underwent noncontrast cardiac CT for CAC score quantification. From CT, epicardial adipose tissue (EAT) volume, left ventricular and left atrial (LA) axial area index, ascending and descending aortic diameters, as well as aortic valve, mitral ring, and thoracic aortic calcification (TAC) were assessed. Incident cardiovascular events included myocardial infarction, stroke, and cardiovascular death. The prognostic value of CT-derived parameters was assessed by Cox regression analysis, receiver operating characteristics, and net reclassification improvement. RESULTS: From 3,630 subjects (59 ± 8 years of age, 46% male), 241 (6.6%) developed a cardiovascular event during 9.9 ± 2.6 years of follow-up. In multivariable Cox regression analysis including Framingham Risk Score, CAC (as log[CAC + 1]), and CT parameters, LA index (hazard ratio [HR]: 1.22 [95% confidence interval [CI]: 1.05 to 1.41] per SD; p = 0.010) and EAT volume (HR: 1.15 [95% CI: 1.01 to 1.30] per SD; p = 0.031) were significantly associated with incident events. In addition, presence of TAC showed an elevated event rate (HR: 1.33 [95% CI: 0.97 to 1.81]; p = 0.08), whereas all other CT-derived parameters showed no relevant association. The LA index, EAT volume, and presence of TAC together improved the prediction of events over Framingham Risk Score and CAC in receiver operating characteristics analysis (area under the curve: 0.749 to 0.764; p = 0.011), and let to a significant net reclassification improvement (HR: 38.0%; 95% CI: 25.1% to 50.8%). CONCLUSION: Assessment of LA index, EAT volume, and TAC from non-contrast-enhanced cardiac CT improves the prediction of incident hard cardiovascular events above CAC and established risk factors, indicating that quantification of these noncoronary measures may improve the prognostic value of this imaging technology.

Resting heart rate is an independent predictor of all-cause mortality in the middle aged general population.

BACKGROUND: High resting heart rate (RHR) predicts cardiovascular outcomes in patients with vascular disease and heart failure. We evaluated the prognostic value of RHR in a large contemporary population-based, prospective cohort of individuals without known coronary artery disease. METHODS AND RESULTS: Resting heart rate (RHR) was determined in 4091 individuals (mean age 59.2 ± 7.7; 53 % women) from the Heinz Nixdorf RECALL study, of whom, 3348 were free of heart rate lowering medication. During 10.5 years of follow-up (median), 159 (3.9 %) individuals developed a coronary event and 398 (9.7 %) died of any cause. Persons without any event (n = 3603) had similar heart rates as persons with coronary events (69.5 ± 11 versus 69.9 ± 11 bpm, p = 0.51) but lower heart rates than persons who died (72.3 ± 13 bpm, p < 0.0001). In individuals without heart rate lowering medication, an increase in heart rate by 5 bpm was associated with an increased hazard ratio (HR) for all-cause mortality of 13 % in unadjusted analysis and also upon adjustment for traditional cardiovascular risk factors, including coronary artery calcification [full model: HR (95 % CI) 1.13 (1.07-1.20), p < 0.0001], but not for coronary events [HR 1.02 (0.94-1.11), p = 0.60]. In individuals without heart rate lowering medication, the HR (full model) for heart rate ≥70 versus <70 bpm with regard to all-cause mortality and coronary events was 1.68 (1.30-2.18), p < 0.0001, and 1.20 (0.82-1.77), p = 0.35. Analysis of the entire cohort revealed a continuous relationship of heart rate with all-cause mortality [HR for lowest to highest heart rate quartile 1.64 (1.22-2.22), p = 0.001, full model] but not with coronary events [HR 1.04 (0.65-1.66), p = 0.86]. CONCLUSIONS: In the general population without known coronary artery disease and heart rate lowering medication, elevated RHR is an independent risk marker for all-cause mortality but not for coronary events.

Progression of coronary artery calcification seems to be inevitable, but predictable - results of the Heinz Nixdorf Recall (HNR) study.

AIM: Coronary artery calcification (CAC), as a sign of atherosclerosis, can be detected and progression quantified using computed tomography (CT). We develop a tool for predicting CAC progression. METHODS AND RESULTS: In 3481 participants (45-74 years, 53.1% women) CAC percentiles at baseline (CACb) and after five years (CAC5y) were evaluated, demonstrating progression along gender-specific percentiles, which showed exponentially shaped age-dependence. Using quantile regression on the log-scale (log(CACb+1)) we developed a tool to individually predict CAC5y, and compared to observed CAC5y. The difference between observed and predicted CAC5y (log-scale, mean±SD) was 0.08±1.11 and 0.06±1.29 in men and women. Agreement reached a kappa-value of 0.746 (95% confidence interval: 0.732-0.760) and concordance correlation (log-scale) of 0.886 (0.879-0.893). Explained variance of observed by predicted log(CAC5y+1) was 80.1% and 72.0% in men and women, and 81.0 and 73.6% including baseline risk factors. Evaluating the tool in 1940 individuals with CACb>0 and CACb<400 at baseline, of whom 242 (12.5%) developed CAC5y>400, yielded a sensitivity of 59.5%, specificity 96.1%, (+) and (-) predictive values of 68.3% and 94.3%. A pre-defined acceptance range around predicted CAC5y contained 68.1% of observed CAC5y; only 20% were expected by chance. Age, blood pressure, lipid-lowering medication, diabetes, and smoking contributed to progression above the acceptance range in men and, excepting age, in women. CONCLUSION: CAC nearly inevitably progresses with limited influence of cardiovascular risk factors. This allowed the development of a mathematical tool for prediction of individual CAC progression, enabling anticipation of the age when CAC thresholds of high risk are reached.

Effect of smoking and other traditional risk factors on the onset of coronary artery calcification: results of the Heinz Nixdorf recall study.

BACKGROUND: Coronary artery calcium (CAC) indicates coronary atherosclerosis and can be present in very early stages of the disease. The conversion from no CAC to any CAC reflects an important step of the disease process as cardiovascular risk is increased in persons even with mildly elevated CAC. We sought to identify risk factors that determined incident CAC>0 in men and women from an unselected general population with a special focus on the role of smoking. METHODS: All 4814 persons that were initially studied in the Heinz Nixdorf Recall Study were invited to participate in the follow-up examination after 5.1 ± 0.3 years. All traditional Framingham risk factors were quantified using standard techniques. Smokers were categorized in never, former and present smokers. The CAC scores were measured from EBCT using the Agatston method. RESULTS: Overall, out of 342 men and 919 women with zero CAC at baseline, 107 (31.3%) men and 210 (22.9%) women had CAC>0 at second examination. In multivariable analysis, age (OR estimate per 5 years: 1.34 (95%CI: 1.21-1.47)), LDL cholesterol (per 10 mg/dL: 1.05 (95%CI: 1.01-1.10)), systolic blood pressure (per 10 mmHg: 1.19 (95%CI: 1.11-1.28)) and current smoking (1.49 (95%CI: 1.04-2.15)) were independent predictors of CAC onset. The probability of CAC onset steadily increased with age from 23.3% (men) and 15.3% (women) at age 45-49 years to 66.7% (men) and 42.9% (women) at age 70-74 years. The difference in age-dependent conversion rates was quantified by years between reaching a given level of CAC onset probability. We found a consistent pattern with respect to smoking status: presently (formerly) smoking middle-aged men convert to positive CAC 10 (5) years earlier than never smokers, for women (middle-aged to elderly) this time span is 8 (5) years. CONCLUSION: Several traditional CVD risk factors are associated with CAC onset during 5 years follow-up. CAC onset is accelerated by approximately 10 (5) years for present (former) compared to never smokers.

Comparison of early postoperative morbidity after robot-assisted and open radical cystectomy: results of a prospective observational study.

OBJECTIVE: To evaluate early postoperative morbidity in patients undergoing either robot-assisted (RARC) or open radical cystectomy (ORC) for bladder cancer. PATIENTS AND METHODS: A total of 100 patients underwent RARC (between August 2009 and August 2012) and 42 underwent ORC (between October 2007 and July 2009) as treatment for bladder cancer. Data on the patients' peri-operative course were collected prospectively up to the 90th postoperative day for the RARC group and up to the 60th postoperative day for the ORC group. Postoperative complications were recorded based on the Clavien-Dindo classification system. Both groups were compared with regard to patient and tumour characteristics, surgical and peri-operative outcomes. RESULTS: The RARC and ORC groups were well matched with regard to age, body mass index, gender distribution, type of urinary diversion and pathological tumour characteristics (all P > 0.1), but patients in the RARC group had more serious comorbidities according to the Charlson comorbidity index (P = 0.034). Although surgical duration was longer in the RARC group (P < 0.001) the estimated blood loss was lower (P < 0.001) and transfusion requirement was less (P < 0.001). Overall 59 patients (59%) in the RARC group and 39 patients (93%) in the ORC group experienced postoperative complications of any Clavien-Dindo grade <90 days and <60 days after surgery, respectively (P < 0.001; relative risk reduction 0.36). Major complications (grades 3a-5) were also less frequent after RARC (24 [24%] vs 18 patients [43%]; P = 0.029) with a relative risk reduction of 0.44. In the subgroup of patients with an ileum conduit as a urinary diversion (RARC, n = 76 vs ORC, n = 31) the overall rate of complications (43 [57%] vs 28 [90%] patients; P < 0.001) and the rate of major complications (17 [22%] vs 15 [48%] patients; P = 0.011) were lower in the RARC group with relative risk reductions of 0.37 and 0.54, respectively. CONCLUSIONS: A significant reduction in early postoperative morbidity was associated with the robotic approach. Despite more serious comorbidities and a 30-day longer follow-up in the RARC group, patients in the RARC group experienced fewer postoperative complications than those in the ORC group. Major complications, in particular, were less frequent after RARC.

Coronary atherosclerosis burden, but not transient troponin elevation, predicts long-term outcome in recreational marathon runners.

We determined the prognostic value of transient increases in high-sensitive serum troponin I (hsTnI) during a marathon and its association with traditional cardiovascular risk factors and imaging-based risk markers for incident coronary events and all-cause mortality in recreational marathon runners. Baseline data of 108 marathon runners, 864 age-matched controls and 216 age- and risk factor-matched controls from the general population were recorded and their coronary event rates and all-cause mortality after 6 ± 1 years determined. hsTnI was measured in 74 marathon finishers before and after the race. Other potential predictors for coronary events, i.e., Framingham Risk Score (FRS), coronary artery calcium (CAC) and presence of myocardial fibrosis as measured by magnetic resonance imaging-based late gadolinium enhancement (LGE), were also assessed. An increase beyond the 99 % hsTnI-threshold, i.e., 0.04 µg/L, was observed in 36.5 % of runners. FRS, CAC, or prevalent LGE did not predict hsTnI values above or increases in hsTnI beyond the median after the race, nor did they predict future events. However, runners with versus without LGE had higher hsTnI values after the race (median (Q1/Q3), 0.08 µg/L (0.04/0.09) versus 0.03 µg/L (0.02/0.06), p = 0.039), and higher increases in hsTnI values during the race (median (Q1/Q3), 0.05 µg/L (0.03/0.08) versus 0.02 µg/L (0.01/0.05), p = 0.0496). Runners had a similar cumulative event rate as age-matched or age- and risk factor-matched controls, i.e., 6.5 versus 5.0 % or 4.6 %, respectively. Event rates in runners with CAC scores <100, 100-399, and ≥400 were 1.5, 12.0, and 21.4 % (p = 0.002 for trend) and not different from either control group. Runners with coronary events had a higher prevalence of LGE than runners without events (57 versus 8 %, p = 0.003). All-cause mortality was similar in marathon runners (3/108, 2.8 %) and controls (26/864, 3.0 % or 5/216, 2.4 %, respectively). Recreational marathon runners with prevalent myocardial fibrosis develop higher hsTnI values during the race than those without. Increasing coronary artery calcium scores and prevalent myocardial fibrosis, but not increases in hsTnI are associated with higher coronary event rates. All-cause mortality in marathon runners is similar to that in risk factor-matched controls.

Association of obstructive sleep apnoea with subclinical coronary atherosclerosis.

BACKGROUND: Accumulating evidence suggests a role of obstructive sleep apnoea (OSA) as a risk factor for coronary atherosclerosis. This study aimed i) to assess the prevalence of OSA in the general population and ii) to analyse the association of this disorder with traditional cardiovascular disease risk factors and subclinical coronary atherosclerosis. METHODS: In a cross-sectional analysis of the Heinz Nixdorf Recall study a subgroup of 1604 subjects (791 men, age 50-80 years) underwent OSA screening. Furthermore, coronary artery calcium (CAC) was measured. OSA was defined as apnoea-hypopnoea index (AHI) ≥ 15/h. RESULTS: OSA was observed in 29.1% of men and 15.6% of women. In a multiple linear regression analysis adjusted for risk factors AHI was associated with CAC in men aged ≤65 years (estimated log-transformed increase of CAC = 0.25, 95% confidence interval (CI) = -0.001-0.50, p = 0.051) and in women of any age (estimated log-transformed increase = 0.23, 95% CI = 0.04-0.41, p = 0.02). Doubling of the AHI was associated with a 19% increase of CAC in men aged ≤65 years and with a 17% increase in women of any age. CONCLUSIONS: In the general population aged ≥50 years OSA is associated with subclinical atherosclerosis in men aged ≤65 years and in women of any age, independent of traditional cardiovascular risk factors.

Does changeover by an experienced open prostatic surgeon from open retropubic to robot-assisted laparoscopic prostatectomy mean a step forward or backward?

We assessed whether changeover from open retropubic [RRP] to robotic-assisted laparoscopic prostatectomy [RALP] means a step forward or backward for the initial RALP patients. Therefore the first 105 RALPs of an experienced open prostatic surgeon and robotic novice-with tutoring in the initial 25 cases-were compared to the most recent 105 RRPs of the same surgeon. The groups were comparable with respect to patient characteristics and postoperative tumor characteristics (all P > 0.09). The only disadvantage of RALP was a longer operating time; the advantages were lower estimated blood loss, fewer anastomotic leakages, earlier catheter removal, shorter hospital stay (all P < 0.04), and less major complications within 90 days postoperatively (P < 0.01). Positive surgical margin rates were comparable both overall and stratified for pT stage in both groups (all P < 0.08). In addition, an equivalent number of lymph nodes were removed (P > 0.07). Twelve months after surgery, patient reported continence and erectile function were comparably good (all P > 0.11). Our study indicates that an experienced open prostatic surgeon and robotic novice who switches to RALP can achieve favorable surgical results despite the initial RALP learning curve. At the same time neither oncological nor functional outcomes are compromised.

Tumour characteristics, oncological and functional outcomes in patients aged ≥ 70 years undergoing radical prostatectomy.

UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The marked increase in life expectancy in recent years calls for reconsideration of the decision-making process for the treatment of prostate cancer, a condition particularly affecting the elderly. To date the general approach in elderly patients has tended to be more conservative, not least as it is generally thought that prostate cancer in these patients is less biologically aggressive. The present data showed that patients aged ≥70 years had biologically more aggressive tumours significantly more often than those aged <70 years. Nevertheless, advanced age itself was not an independent predictor of survival after retropubic radical prostatectomy, whereas adverse prostate cancer features and severe comorbidities were. OBJECTIVE: To investigate the effect of advanced age (≥70 years) on prostate cancer characteristics, oncological and functional outcomes in patients undergoing retropubic radical prostatectomy (RP). PATIENTS AND METHODS: Between June 1997 and September 2009, 1636 patients underwent RP at one institution. Of these patients, 1225 were aged < 70 years and 411 ≥70 years. Both groups were compared for prostate cancer characteristics, oncological and functional outcomes. Multivariate analyses were used to estimate the effect of advanced age on overall survival (OS), cancer-specific survival (CSS), biochemical recurrence-free survival (BFS) and postoperative continence. RESULTS: The median (range) age of the patients aged ≥ 70 years was 72 (70-85) years and for those aged < 70 years was 64 (40-69) years (P < 0.001), respectively. The patients aged ≥ 70 years were assigned higher American Society of Anesthesiologists (ASA) classes (P < 0.001) reflecting a higher rate of severe comorbidities in this group. In the patients aged ≥ 70 years there were significantly more clinically palpable and pathologically non-organ-confined tumours (P= 0.030 and P= 0.026, respectively), and higher biopsy and RP Gleason scores (P= 0.002 and P= 0.004, respectively). Accordingly, patients aged ≥ 70 years presented with a higher proportion of high-risk prostate cancer, although the difference was not significant (P= 0.060). There were no differences between the groups for preoperative prostate-specific antigen level (P= 0.898), rate of pelvic lymph node dissection (P= 0.231), pN+ (P= 0.526) and R+ status (P= 0.590). Kaplan-Meier curves showed a significantly lower 10-year OS (67 vs 82%; P= 0.017) and a trend towards a lower 10-year CSS (70 vs 83%; P= 0.057) in patients aged ≥ 70 years. However, on multivariate analysis advanced age was not an independent predictor of OS (P= 0.102) or CSS (P= 0.195), whereas pN+ status (both P < 0.001), RP Gleason scores 8-10 (both P < 0.001) and ASA classes 3-4 (P= 0.037 and P= 0.028, respectively) were. The 2-year postoperative continence rates was comparable between the groups (International Continence Society [ICS] male incontinence symptom score 2.10 vs 2.01; P= 0.984). In multivariate analysis it depended only on the preoperative ICSmale incontinence symptom score (P < 0.001) but not on advanced age (P= 0.341). CONCLUSIONS: Patients aged ≥ 70 years had biologically more aggressive and locally advanced tumours significantly more often than those aged < 70 years. However, advanced age itself was not an independent predictor of survival after RP. Rather, survival was associated with adverse prostate cancer features and severe comorbidities. Consequently, it seems unjustifiable to generally exclude elderly patients from RP, not least because surgery achieved excellent postoperative continence in this age group, too.

Subclinical coronary atherosclerosis predicts cardiovascular risk in different stages of hypertension: result of the Heinz Nixdorf Recall Study.

Prehypertension is a frequent condition and has been demonstrated to increase cardiovascular risk. However, the association with coronary atherosclerosis as part of target organ damage is not well understood. We investigated the cross-sectional relationship and longitudinal outcome between blood pressure categories and coronary artery calcification (CAC), quantified by electron beam computed tomography, in 4181 participants from the population-based Heinz Nixdorf Recall Study cohort. At baseline, we observed a continuous increase in calcium scores with increasing blood pressure categories. During a median follow-up period of 7.18 years, 115 primary end points (2.8%; fatal and nonfatal myocardial infarction) and 152 secondary end points (3.6%; stroke and coronary revascularization) occurred. We observed a continuous increase in age- and risk factor-adjusted secondary endpoints (hazard ratios [95% CI]) with increasing blood pressure categories (referent: normotension) in men: prehypertension, 1.80 (0.53-6.13); stage 1 hypertension, 2.27 (0.66-7.81); and stage 2 hypertension, 4.10 (1.27-13.24) and in women: prehypertension, 1.13 (0.34-3.74); stage 1 hypertension, 2.14 (0.67-6.85); and stage 2 hypertension, 3.33 (1.24-8.90), respectively, but not in primary endpoints. Cumulative event rates were determined by blood pressure categories and the CAC. In prehypertension, the adjusted hazard ratios for all of the events were, for CAC 1 to 99, 2.05 (0.80-5.23; P=0.13); 100 to 399, 3.12 (1.10-8.85; P=0.03); and ≥400, 7.72 (2.67-22.27; P=0.0002). Risk of myocardial infarction and stroke in hypertension but also in prehypertension depends on the degree of CAC. This marker of target-organ damage might be included, when lifestyle modification and pharmacotherapeutic effects in prehypertensive individuals are tested to avoid exposure to risk and increase benefit.

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.

Association of exercise capacity and the heart rate profile during exercise stress testing with subclinical coronary atherosclerosis: data from the Heinz Nixdorf Recall study.

BACKGROUND: Exercise capacity and heart rate profile parameters obtained from exercise stress testing as well as the subclinical coronary atherosclerosis burden from cardiac CT have been suggested to improve cardiovascular (CV) risk stratification beyond traditional risk factors (RF) in persons at risk of CV events. AIM: To study the association of exercise stress-test variables with the coronary artery calcium (CAC) burden in relation to age, sex and traditional RF in subjects without known coronary artery disease from the general population. METHODS: In 3,163 subjects, CV and RF were measured, a bicycle stress test was performed and the electron beam CT-based CAC-Agatston score was quantified. RESULTS: Exercise capacity, chronotropic response and an abnormal HR recovery were significantly and inversely related to CAC scores in men and women in univariate unadjusted analysis. This association was diminished after adjustment for age and sex and further after adjustment for traditional risk factors. In multivariate analysis, chronotropic response in men [estimate (95% CI): 0.94 (0.91-0.97), P = 0.0005] and an abnormal HR recovery (<15 bpm after 1 min) in women [estimate: 1.34 (1.07-1.70), P = 0.013] but not exercise capacity remained associated with CAC independent of traditional RF. In subjects not taking lipid-lowering, antiarrhythmic or antihypertensive drugs, estimates for the observed associations were essentially unchanged. The clinical ability of these variables to predict a high CAC score was limited. CONCLUSION: The strong inverse association of exercise capacity, chronotropic response and abnormal HR recovery during exercise stress testing with the CAC burden in unadjusted univariate analysis is largely influenced by age, sex and cardiovascular RFs. The degree, to which exercise stress-test variables and the CAC burden independently contribute to the prediction of cardiovascular events, remains to be shown.