Diagnostic Cardiac CT for the Improvement of Cardiovascular Event Prediction.

BACKGROUND: The aim of the long-term Heinz Nixdorf Recall Study (observation period 20 years) was to establish the extent to which computed tomography (CT) improves the predictability of cardiovascular events relative to determination of risk factors alone. METHODS: In the period 2000-2003, study staff examined 4355 probands (53% of them female) aged 45-75 years with no signs of cardiovascular disease. The Atherosclerotic Cardiovascular Disease (ASCVD) score was calculated on the basis of demographic data and cardiovascular risk factors. Cardiac CT was carried out over the same period and coronary artery calcification (CAC) was graded according to the Agatston score. RESULTS: The median duration of follow-up was 18.2 years for men and 17.8 years for women. Myocardial infarction or stroke occurred in 458 (11%) of the 4154 participants with complete data. Overall, estimation of risk using a combination of ASCVD score and CAC grade was superior to the ASCVD score alone-even after 10 and 20 years. Classification into established risk categories improved by 12.2% (95% confidence interval: [5.3%; 18.1%]). In the highest ASCVD risk category, we observed occurrence of a cardiovascular event over 20 years for 14% [5.0%; 23.1%] of probands with a CAC score = 0 but for 34.2% [27.5%; 41.4%] of those with a CAC score ≥ 400. In the lowest ASCVD risk category, an event occurred in 2.4% [1.4%; 3.7%] of probands with a CAC score = 0 and in 23.5% [2.3%; 35.8%] of those with a CAC score ≥ 400. CONCLUSION: Even after 20 years, individual risk prediction is improved by addition of CT-based determination of coronary artery calcification to the ASCVD score. Therefore, assessment of ASCVD risk factors should be complemented more widely by cardiac CT in the primary prevention of cardiovascular disease.

Clinical characteristics and determinants of mortality in coronavirus disease 2019 (COVID-19) patients on an intensive care unit-a retrospective explorative 1-year all-comers study.

Background: Clinical outcome in patients with coronavirus disease 2019 (COVID-19) requiring treatment on intensive care units (ICU) remains unfavourable. The aim of this retrospective study was to exploratively identify potential predictors of unfavourable outcome in ICU patients diagnosed with COVID-19. Methods: In all patients with COVID-19 (n=50) or severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) as comorbidity (n=11) at our ICU we assessed clinical, respiratory and laboratory parameters with a potential role for outcome. Main outcome variables were intubation and mortality rates. Results: Between March 2020 and March 2021, 573 patients were hospitalized with SARS-CoV-2 infection. Of these, 61 patients (10.6%, 44.3% women) aged 66.4±13.3 were admitted to ICU. A proportion of 73.8% of patients had moderate or severe acute respiratory distress syndrome (ARDS). COVID-19 patients differed clinically from those with SARS-CoV-2 as comorbidity, such as severe heart or renal failure or sepsis as the leading cause of ICU admission, despite similar mortality rates (44.0% vs. 45.5%, P>0.5). Among COVID-19 patients, those who died had more often severe ARDS (91% vs. 46%, P=0.001), longer non-invasive ventilation (NIV) therapy prior to ICU (6.3±5.9 vs. 2.5±2.0 days, P=0.046), and higher interleukin-6 (IL-6) and lactate dehydrogenase (LDH) values as compared to survivors. In multivariable analysis, NIV duration ≥5 days on admission [odds ratio (OR): 42.20, 95% confidence interval (CI): 1.22 to >99, P=0.038] and IL-6 [OR: 4.08, 95% CI: 1.16-14.33, P=0.028] remained independently predictive of mortality. In worsening tertiles of partial pressure of oxygen (pO2)/inspiratory oxygen fraction (FiO2) on admission (≥161.5, 96.5 to <161.5, <96.5) we observed a stepwise increase in intubation rates (P=0.0034) and mortality rates (P=0.031). Conclusions: As inflammation, ARDS severity and longer NIV duration prior to ICU are associated with intubation and mortality rates, prognosis appears to be largely determined by disease severity. Whether NIV aggravates ARDS or if it indicates lack of recovery independent from type of ventilation, or both should be clarified in a prospective trial.

Exercise and Coronary Atherosclerosis: Observations, Explanations, Relevance, and Clinical Management.

Physical activity and exercise training are effective strategies for reducing the risk of cardiovascular events, but multiple studies have reported an increased prevalence of coronary atherosclerosis, usually measured as coronary artery calcification, among athletes who are middle-aged and older. Our review of the medical literature demonstrates that the prevalence of coronary artery calcification and atherosclerotic plaques, which are strong predictors for future cardiovascular morbidity and mortality, was higher in athletes compared with controls, and was higher in the most active athletes compared with less active athletes. However, analysis of plaque morphology revealed fewer mixed plaques and more often only calcified plaques among athletes, suggesting a more benign composition of atherosclerotic plaques. This review describes the effects of physical activity and exercise training on coronary atherosclerosis in athletes who are middle-aged and older and aims to contribute to the understanding of the potential adverse effects of the highest doses of exercise training on the coronary arteries. For this purpose, we will review the association between exercise and coronary atherosclerosis measured using computed tomography, discuss the potential underlying mechanisms for exercise-induced coronary atherosclerosis, determine the clinical relevance of coronary atherosclerosis in middle-aged athletes and describe strategies for the clinical management of athletes with coronary atherosclerosis to guide physicians in clinical decision making and treatment of athletes with elevated coronary artery calcification scores.

Cardiac computed tomography in patients with symptomatic new-onset atrial fibrillation, rule-out acute coronary syndrome, but with intermediate pretest probability for coronary artery disease admitted to a chest pain unit.

BACKGROUND: Atrial fibrillation (AF) and coronary artery disease (CAD) may be encountered coincidently in a large portion of patients. However, data on coronary artery calcium burden in such patients are lacking. Thus, we sought to determine the value of cardiac computed tomography (CCT) in patients presenting with new-onset AF associated with an intermediate pretest probability for CAD admitted to a chest pain unit (CPU). METHODS: Calcium scores (CS) of 73 new-onset, symptomatic AF subjects without typical clinical, electrocardiographic, or laboratory signs of acute coronary syndrome (ACS) admitted to our CPU were analyzed. In addition, results from computed tomography angiography (CTA) were related to coronary angiography findings whenever available. RESULTS: Calcium scores of zero were found in 25%. Median Agatston score was 77 (interquartile range: 1-270) with gender- and territory-specific dispersal. CS scores above average were present in about 50%, high (> 400)-to-very high (> 1000) CS scores were found in 22%. Overall percentile ranking showed a relative accordance to the reference percentile distribution. Additional CTA was performed in 47%, revealing stenoses in 12%. Coronary angiography was performed in 22% and resulted in coronary intervention or surgical revascularization in 7%. On univariate analysis, CS > 50th percentile failed to serve as an independent determinant of significant stenosis during catheterization. CONCLUSIONS: Within a CPU setting, relevant CAD was excluded or confirmed in almost 50%, the latter with a high proportion of coronary angiographies and subsequent coronary interventions, underlining the diagnostic value of CCT in symptomatic, non-ACS, new-onset AF patients when admitted to a CPU.

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.

Association of Coronary Artery Calcium Score vs Age With Cardiovascular Risk in Older Adults: An Analysis of Pooled Population-Based Studies.

Importance: Besides age, other discriminators of atherosclerotic cardiovascular disease (ASCVD) risk are needed in older adults. Objectives: To examine the predictive ability of coronary artery calcium (CAC) score vs age for incident ASCVD and how risk prediction changes by adding CAC score and removing only age from prediction models. Design, Setting, and Participants: We conducted an analysis of pooled US population-based studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Results were compared with 2 European cohorts, the Rotterdam Study and the Heinz Nixdorf Recall Study. Participants underwent CAC scoring between 1998 and 2006 using cardiac computed tomography. The participants included adults older than 60 years without known ASCVD at baseline. Exposures: Coronary artery calcium scores. Main Outcomes and Measures: Incident ASCVD events including coronary heart disease (CHD) and stroke. Results: The study included 4778 participants from 3 US cohorts, with a mean age of 70.1 years; 2582 (54.0%) were women, and 2431 (50.9%) were nonwhite. Over 11 years of follow-up (44 152 person-years), 405 CHD and 228 stroke events occurred. Coronary artery calcium score (vs age) had a greater association with incident CHD (C statistic, 0.733 vs 0.690; C statistics difference, 0.043; 95% CI of difference, 0.009-0.075) and modestly improved prediction of incident stroke (C statistic, 0.695 vs 0.670; C statistics difference, 0.025; 95% CI of difference, -0.015 to 0.064). Adding CAC score to models including traditional cardiovascular risk factors, with only age being removed, provided improved discrimination for incident CHD (C statistic, 0.735 vs 0.703; C statistics difference, 0.032; 95% CI of difference, 0.002-0.062) but not for stroke. Coronary artery calcium score was more likely than age to provide higher category-free net reclassification improvement among participants who experienced an ASCVD event (0.390; 95% CI, 0.312-0.467 vs 0.08; 95% CI -0.001 to 0.181) and to result in more accurate reclassification of risk for ASCVD events among these individuals. The findings were similar in the 2 European cohorts (n = 4990). Conclusions and Relevance: Coronary artery calcium may be an alternative marker besides age to better discriminate between lower and higher CHD risk in older adults. Whether CAC score can assist in guiding the decision to initiate statin treatment for primary prevention in older adults requires further investigation.

Comparison of coronary artery calcification, carotid intima-media thickness and ankle-brachial index for predicting 10-year incident cardiovascular events in the general population.

AIMS: To compare the predictive value of coronary artery calcification (CAC), carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) in a primary prevention cohort depending on risk factor profile to determine which of the three markers improves cardiovascular (CV) risk discrimination best in which risk group. METHODS AND RESULTS: We quantified CAC, CIMT, and ABI in 3108 subjects (mean age 59.2 ± 7.7, 47.1% male) without prevalent CV diseases from the population-based Heinz Nixdorf Recall study. Associations with incident major CV events (coronary event, stroke, CV death; n = 223) were assessed during a follow-up period of 10.3 ± 2.8 years with Cox proportional regressions in the total cohort and stratified by Framingham risk score (FRS) groups. Discrimination ability was evaluated with Harrell's C. All three markers were associated with CV events (hazard ratio [95% confidence interval (CI)]: CAC: 1.31 (1.23-1.39) per 1-unit increase in log(CAC + 1) vs. CIMT: 1.27 (1.13-1.43) per 1 SD vs. ABI: 1.30 (1.14-1.49) per 1 SD, in FRS adjusted models). Considering reclassification, CAC lead to highest reclassification in the total cohort, while also for CIMT and ABI significant improvement in net-reclassification was observed [NRI (95% CI): CAC: 0.55 (0.42-0.69); CIMT: 0.32 (0.19-0.45); ABI: 0.19 (0.10-0.28)]. CONCLUSION: Coronary artery calcification provides the best discrimination of risk compared with CIMT and ABI, particularly in the intermediate risk group, whereas CIMT may be an alternative measure for reassurance in the low risk group.

Endoaneurysmorrhaphy for a Giant Inferobasal Left Ventricular Aneurysm Restoring Mitral Function.

Over the years, the surgery of ventricular postinfarction aneurysm has evolved from linear resection to endoaneurysmorrhaphy using a patch. Technically, several aims that include the restoration of ventricular shape and function, exclusion of dead space, minimization of the risk of thrombus formation and restoration of valve function are pursued. Herein is reported the case of a 58-year-old male with a giant inferobasal aneurysm involving the mitral valve apparatus who underwent successful endoaneurysmorrhaphy. Correct sizing of the patch proved to be the 'road to success' in this patient. The present case is the second reported instance of a giant ventricular aneurysm involving the mitral valve, with favorable outcome.

CAC Score Improves Coronary and CV Risk Assessment Above Statin Indication by ESC and AHA/ACC Primary Prevention Guidelines.

OBJECTIVES: The aim of this study was to assess the difference in indication for statin therapy by European Society of Cardiology (ESC) versus American Heart Association/American College of Cardiology (AHA/ACC) guidelines and to quantify the potential additional role of coronary artery calcification (CAC) score over updated guidelines in a primary prevention cohort. BACKGROUND: Recently, ESC and AHA/ACC updated the guidelines regarding statin therapy in primary prevention. METHODS: In 3,745 subjects (59 ± 8 years of age, 47% men) from the population based longitudinal Heinz Nixdorf Recall cohort study without cardiovascular disease or lipid-lowering therapy at baseline CAC score was assessed between 2000 and 2003. Subjects remained unaware of their initial CAC score. Statin indication was determined according to 2012 ESC and 2013 AHA/ACC guidelines based on subjects individual baseline characteristics. RESULTS: The frequency of statin recommendation was lower according to ESC compared to AHA/ACC guidelines (34% vs. 56%; p < 0.0001), whereas low CAC score (<100) was common in subjects with statin indication by both guidelines (59% for ESC, 62% for AHA/ACC). During 10.4 ± 2.0 years of follow-up, 131 myocardial infarctions occurred. For ESC recommendations, CAC score differentiated risk for subjects without (1.0 [95% confidence interval (CI): 0.4 to 1.5] vs. 6.5 [95% CI: 4.1 to 8.9] coronary events per 1,000 person-years for CAC 0 vs. ≥100) and with statin indication (2.6 [95% CI: 0.6 to 4.7] vs. 9.9 [95% CI: 7.3 to 12.5] per 1,000 person-years for CAC 0 vs. ≥100). Likewise, CAC score stratified proportions experiencing events subjects with statin indication according to AHA/ACC (2.7 [95% CI: 1.1 to 4.2] vs. 9.1 [95% CI: 7.0 to 11.0] per 1,000 person-years for CAC 0 vs. ≥100), whereas event rate in subjects without statin indication was low (1.1 [95% CI: 0.65 to 1.68] per 1,000 person-years). CONCLUSIONS: Current ESC and AHA/ACC guidelines lead to markedly different recommendation regarding statin therapy in a German primary prevention cohort. Quantification of CAC score in addition to the guidelines improves stratification between subjects at high versus low risk for coronary events, indicating that CAC scoring may help to match intensified risk factor modification to atherosclerotic plaque burden as well as actual risk while avoiding therapy in subjects with low coronary atherosclerosis that have low 10-year event rate.

Prevalence and Prognostic Implications of Coronary Artery Calcification in Low-Risk Women: A Meta-analysis.

Importance: The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low cardiovascular disease (CVD) risk based on the American College of Cardiology and American Heart Association CVD prevention guidelines is unclear. Objective: To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women. Design, Setting, and Participants: Women with 10-year atherosclerotic CVD (ASCVD) risk lower than 7.5% from 5 large population-based cohorts: the Dallas Heart Study (United States), the Framingham Heart Study (United States), the Heinz Nixdorf Recall study (Germany), the Multi-Ethnic Study of Atherosclerosis (United States), and the Rotterdam Study (the Netherlands). The 5 cohorts were selected based on the availability of CAC data in a sizable group of low-risk women from the general population together with the long detailed follow-up data. Across the cohorts, events were assessed from the date of CAC scan (performed from 1998 through 2006) until January 1, 2012; January 1, 2014; or March 6, 2015. Fixed-effects meta-analysis was conducted to combine the results of the 5 studies. Exposures: CAC score by computed tomography. Main Outcomes and Measures: Main outcome was incident ASCVD, including nonfatal myocardial infarction, coronary heart disease (CHD) death, and stroke. Association of CAC with ASCVD was examined using Cox proportional hazards models. To assess whether CAC was associated with improved ASCVD risk predictions beyond the traditional risk factors, the C statistic and the continuous net reclassification improvement (cNRI) index were calculated. Results: Among 6739 women with low ASCVD risk from the 5 studies, mean age ranged from 44 to 63 years and CAC was present in 36.1%. Across the cohorts, median follow-up ranged from 7.0 to 11.6 years. A total of 165 ASCVD events occurred (64 nonfatal myocardial infarctions, 29 CHD deaths, and 72 strokes), with the ASCVD incidence rates ranging from 1.5 to 6.0 per 1000 person-years. Compared with the absence of CAC (CAC = 0), presence of CAC (CAC >0) was associated with an increased risk of ASCVD (incidence rates per 1000 person-years, 1.41 for CAC absence vs 4.33 for CAC presence; difference, 2.92 [95% CI, 2.02-3.83]; multivariable-adjusted hazard ratio, 2.04 [95% CI, 1.44-2.90]). The addition of CAC to traditional risk factors improved the C statistic from 0.73 (95% CI, 0.69-0.77) to 0.77 (95% CI, 0.74-0.81) and provided a cNRI of 0.20 (95% CI, 0.09-0.31) for ASCVD prediction. Conclusions and Relevance: Among women at low ASCVD risk, CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors. Further research is needed to assess the clinical utility and cost-effectiveness of this additional accuracy.

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.

Depressive symptoms, life satisfaction and prevalence of sleep disturbances in the general population of Germany: results from the Heinz Nixdorf Recall study.

OBJECTIVES: It appears that not only depression, but also low life satisfaction (LS), is related to sleep disorder in the general population. We evaluate whether the prevalence of sleep disorder attributable to depressed mood is greater among participants with low LS. SETTING, PARTICIPANTS AND OUTCOME MEASURES: Analysis of cross-sectional data from 3880 cohort members from the German Heinz Nixdorf Recall study (2006-2008) aged 51-81 years. Standard mood (Center for Epidemiological Studies Depression scale (CES-D) for Depressive symptoms and a single-item life satisfaction measure) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) measures were conducted as part of the survey. Multiple imputation was used to deal with missing data in outcome, exposures or covariates. Relative excess risk for interaction (RERI) and its 95% CIs were estimated using adjusted prevalence ORs. Owing to the study size, the precision of the measures of additive interaction is relatively low. RESULTS: We observed an association between depressed mood (5-units increase in CES-D score) (POR=1.7 (95% CI 1.6 to 1.8)) and sleep disorder, and between low LS (not very satisfied vs very satisfied) (POR=1.5 (1.1 to 2.2)) and sleep disorder. Also, we observed a synergistic effect between lower level of LS (not very satisfied) and depressed mood (score ≥ 16) on prevalence of sleep disorders (RERI=3.7 (-0.2 to 7.1)). Furthermore, these findings were corroborated in sensitivity analysis carried out with the complete case data set and in sex-specific analyses (RERI=5.5 (-0.4 to 11.3), and RERI=2.4 (-2.5 to 7.4) for men and women, respectively). CONCLUSIONS: Both depressed mood and LS are notably associated with sleep quality, and these relationships are best captured by considering their joint effects. Depression and LS need to be taken into consideration when analysing sleep quality.

Long-term residential exposure to urban air pollution, and repeated measures of systemic blood markers of inflammation and coagulation.

BACKGROUND: In several studies, exposure to fine particulate matter (PM) has been associated with inflammation, with inconsistent results. We used repeated measurements to examine the association of long-term fine and ultrafine particle exposure with several blood markers of inflammation and coagulation. METHODS: We used baseline (2000-2003) and follow-up (2006-2008) data from the Heinz Nixdorf Recall Study, a German population-based prospective cohort of 4814 participants. A chemistry transport model was applied to model daily surface concentrations of PM air pollutants (PM10, PM2.5) and particle number on a grid of 1 km(2). Applying mixed regression models, we analysed associations of long-term (mean of 365 days prior to blood draw) particle exposure at each participant's residence with the level of high-sensitivity C reactive protein (hs-CRP), fibrinogen, platelet and white cell count (WCC), adjusting for short-term PM exposure (moving averages of 1-7 days), personal characteristics, season, ambient temperature (1-5 days), ozone and time trend. RESULTS: We analysed 6488 observations: 3275 participants with baseline data and 3213 with follow-up data. An increase of 2.4 µg/m(3) in long-term PM2.5 was associated with an adjusted increase of 5.4% (95% CI 0.6% to 10.5%) in hs-CRP and of 2.3% (95% CI 1.4% to 3.3%) in the platelet count. Fibrinogen and WCC were not associated with long-term particle exposure. CONCLUSIONS: In this population-based cohort, we found associations of long-term exposure to PM with markers of inflammation (hs-CRP) and coagulation (platelets). This finding supports the hypothesis that inflammatory processes might contribute to chronic effects of air pollution on cardiovascular disease.

Association of short-term ozone and temperature with sleep disordered breathing.

Scarce evidence suggests that ambient air pollution and temperature might play a role in incidence and severity of sleep disordered breathing (SDB). We investigated the association of short-term exposure to fine particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10)), ozone and temperature with SDB in the general population. Between 2006 and 2008, 1773 participants (aged 50-80 years) of the Heinz Nixdorf Recall study underwent screening for SDB, as defined by the apnoea-hypopnoea index (AHI). We assessed daily exposure to PM10, ozone, temperature and humidity. We used multiple linear regression to estimate associations of daily PM10, ozone levels and temperature on the day of screening, adjusting for relative humidity, season, age, sex, body mass index, education, smoking habits, alcohol consumption and physical activity. In the study population, the mean±sd AHI was 11.2±11.4 events·h(-1). Over all seasons, an interquartile range increase in temperature (8.6°C) and ozone (39.5 µg·m(-3)) was associated with a 10.2% (95% CI 1.2-20.0%) and 10.1% (95% CI 2.0-18.9%) increase in AHI, respectively. Associations for temperature were stronger in summer, yielding a 32.4% (95% CI 0.0-75.3%) increase in AHI per 8.6°C (p-value for season-temperature interaction 0.08). We observed that AHI was not associated with PM10. This study suggests that short-term variations in ozone concentration and temperature are associated with SDB.