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Aims: The association between lung function and cardiac markers and heart failure (HF) has been little studied in the general older population. We have examined the association between lung function and airway obstruction with cardiac markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) and risk of incident HF in older men., Methods and Results: Prospective study of 3242 men aged 60-79 years without prevalent HF or myocardial infarction followed up for an average period of 13 years, in whom 211 incident HF cases occurred. Incident HF was examined in relation to % predicted FEV1 and FVC. The Global Initiative on Obstructive Lung Diseases spirometry criteria were used to define airway obstruction. Reduced FEV1, but not FVC in the normal range, was significantly associated with increased risk of HF after adjustment for established HF risk factors including inflammation. The adjusted HRs comparing men in the 6-24th percentile with the highest quartile were 1.91 (1.24 to 2.94) and 1.30 (0.86 to 1.96) for FEV1 and FVC, respectively. FEV1 and FVC were inversely associated with NT-proBNP and cTnT, although the association between FEV1 and incident HF remained after adjustment for NT-proBNP and cTnT. Compared with normal subjects (FEV1/FVC ≥0.70 and FVC≥80%), moderate or severe (FEV1/FVC <0.70 and FEV1 <80%) airflow obstruction was independently associated with HF ((adjusted relative risk 1.59 (1.08 to 2.33)). Airflow restriction (FEV1/FVC ≥0.70 and FVC <80%) was not independently associated with HF., Conclusions: Reduced FEV1 reflecting airflow obstruction is associated with cardiac dysfunction and increased risk of incident HF in older men., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

We tested the predictive ability of cardiac biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T, and midregional pro adrenomedullin for cardiovascular disease (CVD) events using the British Regional Heart Study (BRHS) of men aged 60 to 79 years, and the MIDSPAN Family Study (MFS) of men and women aged 30 to 59 years. They included 3757 and 2226 participants, respectively, and during median 13.0 and 17.3 years follow-up the primary CVD event rates were 16.6 and 5.3 per 1000 patient-years, respectively. In Cox models adjusted for basic classical risk factors, 1 SD increases in log-transformed NT-proBNP, high-sensitivity troponin T, and midregional pro adrenomedullin were generally associated with increased primary CVD risk in both the studies (P<0.006) except midregional pro adrenomedullin in MFS (P=0.10). In BRHS, QRISK2 risk factors yielded a C-index of 0.657, which was improved by 0.017 (P=0.005) by NT-proBNP, but not by other biomarkers. Using 28% 14-year risk as a proxy for 20% 10-year risk, NT-proBNP improved risk classification for primary CVD cases (case net reclassification index, 5.9%; 95% confidence interval, 2.8%-9.2%), but only improved classification of noncases at a 14% 14-year risk threshold (4.6%; 2.9%-6.3%). In MFS, ASSIGN risk factors yielded a C-index of 0.752 for primary CVD; none of the cardiac biomarkers improved the C-index. Improvements in risk classification were only seen using NT-proBNP and high-sensitivity troponin T among cases using the 28% 14-year risk threshold (4.7%; 1.0%-9.2% and 2.6%; 0.0%-5.8%, respectively). In conclusion, the improvement in treatment allocation gained by adding cardiac biomarkers to risk scores seems to depend on the risk threshold chosen for commencing preventative treatments., (© 2015 The Authors.)

The trajectories of physical activity (PA) from midlife into old age and their associations with established and novel cardiovascular disease (CVD) risk factors in later life remain unclear. This study examined associations between 20-year nonoccupational PA trajectories and a range of CVD biomarkers at ages 60–79 years. We used data from a sample of 3,331 men (mean baseline age = 50.2 ± 5.8 years) recruited in 1978–1980, with follow-up after 12, 16, and 20 years, reporting habitual nonoccupational PA at each wave. At the 20-year follow-up, surviving men attended a physical examination and provided a fasting blood sample. Group-based trajectory modeling was used to identify trajectories. Adjusted regression analyses examined the association between trajectory-group membership and several cardiometabolic, cardiac, and inflammatory markers at follow-up. Three distinct 20-year trajectories were identified: low/decreasing (21.3%), light/stable (51.8%), and moderate/increasing (27.0%). Compared with the low/decreasing group, membership in the light/stable and moderate/increasing trajectory groups was associated with a more favorable cardiometabolic profile and lower levels of inflammation and endothelial dysfunction. Although following a moderate-increasing PA trajectory was most favorable, more modest but sustained doses of PA into old age may be sufficient to lower CVD risk. [ABSTRACT FROM AUTHOR]

Background and aims The soluble receptor for advanced glycation end products (sRAGE) has been implicated in diabetic vascular complications. We have examined the association between sRAGE and cardiac markers [NT-proBNP and cardiac troponin T (cTnT)] and subclinical vascular markers in older men with and without diabetes. Methods We performed a cross-sectional study of 1159 men aged 71–92 years with no history of cardiovascular disease (myocardial infarction, stroke, heart failure, coronary artery bypass graft operation or angioplasty). Prevalent diabetes included men with a doctor diagnosis of diabetes, men with fasting glucose ≥7 mmol/l or HbA1c ≥ 6.5% (N = 180). Subclinical vascular measurements included carotid intima media thickness (cIMT), arterial stiffness [pulse wave velocity (PWV)], central aortic blood pressure and arterial wave reflections [central augmentation pressure (AP) and augmentation index (AIx)]. Results sRAGE was strongly and positively associated with renal dysfunction in men with and without diabetes. sRAGE was significantly and positively associated with NT-proBNP (but not cTnT) and AP and AIx in both groups of men after adjustment for CVD risk and metabolic risk markers, renal function and inflammation. However, no association was seen between sRAGE and central aortic blood pressure, cIMT or arterial stiffness as determined by PWV in either group. Conclusions Higher plasma sRAGE was associated with increased NT-proBNP and markers of arterial wave reflections in men both with and without diabetes. Increased sRAGE may contribute to or be a marker of worsening cardiac dysfunction or HF. Further studies with cardiac imaging data are required to confirm this. [ABSTRACT FROM AUTHOR]

Objectives: This research investigates the associations between body mass index (BMI) at 21, 40–59, 60–79 years of age on cardiometabolic risk markers at 60–79 years. Methods: A prospective study of 3464 British men with BMI measured at 40–59 and 60–79 years, when cardiometabolic risk was assessed. BMI at 21 years was ascertained from military records, or recalled from middle-age (adjusted for reporting bias); associations between BMI at different ages and later cardiometabolic risk markers were examined using linear regression. Sensitive period, accumulation and mobility life course models were devised for high BMI (defined as BMI≥75th centile) and compared with a saturated BMI trajectory model. Results: At ages 21, 40–59 and 60–79 years, prevalences of overweight (BMI≥25 kg/m2) were 12%, 53%, 70%, and obesity (≥30 kg/m2) 1.6%, 6.6%, and 17.6%, respectively. BMI at 21 years was positively associated with serum insulin, blood glucose, and HbA1c at 60–79 years, with increases of 1.5% (95%CI 0.8,2.3%), 0.4% (0.1,0.6%), 0.3% (0.1,0.4%) per 1 kg/m2, respectively, but showed no associations with blood pressure or blood cholesterol. However, these associations were modest compared to those between BMI at 60–79 years and serum insulin, blood glucose and HbA1c at 60–79 years, with increases of 8.6% (8.0,9.2%), 0.7% (0.5,0.9%), and 0.5% (0.4,0.7%) per 1 kg/m2, respectively. BMI at 60–79 years was also associated with total cholesterol and blood pressure. Associations for BMI at 40–59 years were mainly consistent with those of BMI at 60–79 years. None of the life course models fitted the data as well as the saturated model for serum insulin. A sensitive period at 50 years for glucose and HbA1c and sensitive period at 70 years for blood pressure were identified. Conclusions: In this cohort of men who were thin compared to more contemporary cohorts, BMI in later life was the dominant influence on cardiovascular and diabetes risk. BMI in early adult life may have a small long-term effect on diabetes risk. [ABSTRACT FROM AUTHOR]

Objectives To examine the independent relationships between fibrin D-dimer, interleukin 6 ( IL-6), C-reactive protein ( CRP), and fibrinogen and incident mobility limitation and mortality. Design Prospective. Setting General practice in 24 British towns. Participants Men aged 60 to 79 without prevalent heart failure followed up for an average of 11.5 years (N = 3,925). Measurements All-cause mortality (n = 1,286) and self-reported mobility disability obtained at examination in 1998 to 2000 and in a postal questionnaire 3 to 5 years later in 2003. Results High D-dimer (top vs lowest tertile: adjusted odds ratio ( aOR) = 1.46, 95% confidence interval = 1.02-2.05) and IL-6 (a OR = 1.43, 95% CI = 1.01-2.02) levels (but not CRP or fibrinogen) were associated with greater incident mobility limitation after adjustment for confounders and prevalent disease status. IL-6, CRP, fibrinogen, and D-dimer were significantly associated with total mortality after adjustment for confounders. Only D-dimer and IL-6 predicted total mortality independent of each other and the other biomarkers. The adjusted hazard ratio ( aHR) was 1.16 (95% CI = 1.10-1.22) for a standard deviation increase in log D-dimer and 1.10 (95% CI = 1.04-1.18) for a standard deviation increase in log IL-6. D-dimer was independently related to vascular and nonvascular mortality, and IL-6 was independently related to vascular mortality. Risks of mobility limitation and mortality were greatest in those with a combination of high D-dimer and IL-6 levels. Conclusion D-dimer and IL-6 are associated with risk of mobility limitation and mortality in older men without heart failure. The findings suggest that coagulation leads to functional decline and mortality s that inflammation does not explain. [ABSTRACT FROM AUTHOR]

Objectives To examine associations between habitual physical activity ( PA) and changes in PA and onset of coronary heart disease ( CHD) and the pathways linking PA to CHD. Design British Regional Heart Study population-based cohort; men completed questionnaires in 1996 and 1998 to 2000, attended rescreen in 1998 to 2000, and were followed up to June 2010. Setting Community. Participants Of 4,252 men recruited from primary care centers (77% of those invited and eligible) who were rescreened in 1998 to 2000, 3,320 were ambulatory and free from CHD, stroke, and heart failure and participated in the current study. Measurements Usual PA (regular walking and cycling, recreational activity and sport). Outcome was first fatal or nonfatal myocardial infarction. Results In 3,320 ambulatory men, 303 first and 184 fatal CHD events occurred during a median of 11 years of follow-up; 9% reported no usual PA, 23% occasional PA, and 68% light or more-intense PA. PA was inversely associated with novel risk markers C-reactive protein, D-dimer, von Willebrand Factor and N-terminal pro-brain natriuretic peptide ( NT-pro BNP). Compared with no usual PA, hazard ratios ( HRs) for CHD events, adjusted for age and region, were 0.52 (95% confidence interval ( CI) = 0.34-0.79) for occasional PA, 0.47 (95% CI = 0.30-0.74) for light PA, 0.51 (95% CI = 0.32-0.82) for moderate PA, and 0.44 (95% CI = 0.29-0.65) for moderately vigorous or vigorous PA ( P for linear trend = .004). Adjustment for established and novel risk markers somewhat attenuated HRs and abolished linear trends. Compared with men who remained inactive, men who maintained at least light PA had an HR for CHD events of 0.73 (95% CI = 0.53-1.02) and men whose PA level increased had an HR of 0.86 (95% CI = 0.55-1.35). Conclusion Even light PA was associated with significantly lower risk of CHD events in healthy older men, partly through inflammatory and hemostatic mechanisms and cardiac function ( NT-pro BNP). [ABSTRACT FROM AUTHOR]