Association of Life's Simple 7 lifestyle metric with cardiometabolic disease-free life expectancy in older British men.

BACKGROUND: Cardiometabolic diseases (CMD), including myocardial infarction, stroke, and type 2 diabetes, are leading causes of disability and mortality globally, particularly for people at an older age. The impact of adhering to the Life's Simple 7 (LS7) on the number of years an individual will live without CMD in older adults remains less studied. METHODS: This study included a cohort of 2662 British men aged 60-79 years free of CMD at baseline from the British Regional Heart Study (BRHS). Each LS7 factor (BMI, blood pressure, blood glucose, total cholesterol, smoking, physical activity, and diet) was categorized as poor, intermediate, or ideal, and a composite LS7 adherence was determined by summing the number of LS7 ideal levels achieved. Flexible parametric Royston-Parmar proportional-hazards model was applied to estimate CMD-free life expectancy. RESULTS: Here we show that compared to men with the lowest LS7 adherence [with 18.42 years (95% CI: 16.93, 19.90) of CMD-free life at age 60], men having an ideal LS7 adherence are estimated to gain an additional 4.37 years (95% CI: 2.95, 5.79) of CMD-free life. The CMD-free life gain benefits are consistent across social class groups of manual and non-manual workers. Among LS7 factors, achieving an ideal physical activity provides the largest CMD-free survival benefit: 4.84 years (95% CI: 3.37, 6.32) of additional CMD-free life compared with the physically inactive group. CONCLUSIONS: Our study quantifies and highlights the benefits of adhering to the LS7 ideal levels for living a longer life without CMD in older adults.

Cardiometabolic diseases, including heart attack, stroke, and type 2 diabetes, are leading causes of disability and deaths globally. To benefit cardiometabolic health, the American Heart Association made a number of recommendations, known as the Life's Simple 7 lifestyle metric, including not smoking, having adequate physical activity, following a healthy diet pattern, and managing healthy body weight, healthy blood pressure, cholesterol, and blood sugar levels. Our study showed that adopting a healthy lifestyle following these recommendations could potentially increase the cardiometabolic disease-free life expectancy by more than four years for British men at age 60, with achieving an ideal physical activity level provided the largest survival benefit. Our findings highlight the need for public health efforts and interventions to support older adults in achieving optimal cardiometabolic health, particularly with regards to physical activity.

Influence of neighborhood-level socioeconomic deprivation and individual socioeconomic position on risk of developing type 2 diabetes in older men: a longitudinal analysis in the British Regional Heart Study cohort.

INTRODUCTION: Evidence from longitudinal studies on the influence of neighborhood socioeconomic deprivation in older age on the development of type 2 diabetes mellitus (T2DM) is limited. This study investigates the prospective associations of neighborhood-level deprivation and individual socioeconomic position (SEP) with T2DM incidence in older age. RESEARCH DESIGN AND METHODS: The British Regional Heart Study studied 4252 men aged 60-79 years in 1998-2000. Neighborhood-level deprivation was based on the Index of Multiple Deprivation quintiles for participants' 1998-2000 residential postcode. Individual SEP was defined as social class based on longest-held occupation. A cumulative score of individual socioeconomic factors was derived. Incident T2DM cases were ascertained from primary care records; prevalent cases were excluded. Cox proportional hazard models were used to examine the associations. RESULTS: Among 3706 men, 368 incident cases of T2DM were observed over 18 years. The age-adjusted T2DM risk increased from the least deprived quintile to the most deprived: HR per quintile increase 1.14 (95% CI 1.06 to 1.23) (p=0.0005). The age-adjusted T2DM HR in social class V (lowest) versus social class I (highest) was 2.45 (95% CI 1.36 to 4.42) (p=0.001). Both associations attenuated but remained significant on adjustment for other deprivation measures, becoming non-significant on adjustment for body mass index and T2DM family history. T2DM risk increased with cumulative individual adverse socioeconomic factors: HR per point increase 1.14 (95% CI 1.05 to 1.24). CONCLUSIONS: Inequalities in T2DM risk persist in later life, both in relation to neighborhood-level and individual-level socioeconomic factors. Underlying modifiable risk factors continue to need to be addressed in deprived older age populations to reduce disease burden.

Association of night-time sleep duration and daytime napping with all-cause and cause-specific mortality in older British men: Findings from the British Regional HeartStudy.

Short and long night-time sleep and daytime napping in young and middle-aged populations were associated with increased mortality, but it is unclear in very older people. The aim of this prospective study was to assess the associations in people aged >70 years. We examined the data of British Regional Heart Study, which included 1722 men aged 71-92 years and had night-time sleep duration and daytime napping measured at baseline and were followed up for nine years. There were 597 deaths. Compared to night-time sleep at 7-<8 h, age-adjusted hazard ratio of all-cause mortality in participants sleeping <6 h was 1.04 (95% CI 0.80-1.35), 1.07 (0.85-1.34) in 6-<7 h, 1.04 (0.83-1.30) in 8-<9 h and 0.93 (0.65-1.33) in ≥9 h. Further adjustments for other co-variables still showed no association, and neither the association with cardiovascular mortality nor non-cardiovascular mortality. Daytime napping, however, was associated with mortality. After adjustment for age, smoking, physical activity, obesity, cardiovascular diseases, diabetes, frailty, general health, anti-hypertensive medication and C-reactive protein level, hazard ratio of all-cause mortality in participants with daytime napping >1-h versus no napping was 1.62 (1.18-2.22) and hazard ratio of non-cardiovascular mortality was 1.77 (1.22-2.57). The fully adjusted hazard ratio of cardiovascular mortality was not significantly increased 1.26 (0.69-2.28), although age-adjusted hazard ratio was significant 1.94 (1.20-3.16). In the elderly men, daytime napping was independently associated with increased all-cause and non-cardiovascular mortality, while its association with cardiovascular mortality could be explained by cardiovascular risk factors and co-morbidities. Night-time sleep duration was not associated with mortality risk.

Prospective associations between diet quality, dietary components, and risk of cardiometabolic multimorbidity in older British men.

PURPOSE: Cardiometabolic multimorbidity (CMM) is a major public health challenge. This study investigated the prospective relationships between diet quality, dietary components, and risk of CMM in older British men. METHODS: We used data from the British Regional Heart Study of 2873 men aged 60-79 free of myocardial infarction (MI), stroke, and type 2 diabetes (T2D) at baseline. CMM was defined as the coexistence of two or more cardiometabolic diseases, including MI, stroke, and T2D. Sourcing baseline food frequency questionnaire, the Elderly Dietary Index (EDI), which was a diet quality score based on Mediterranean diet and MyPyramid for Older Adults, was generated. Cox proportional hazards regression and multi-state model were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 19.3 years, 891 participants developed first cardiometabolic disease (FCMD), and 109 developed CMM. Cox regression analyses found no significant association between baseline EDI and risk of CMM. However, fish/seafood consumption, a dietary component of the EDI score, was inversely associated with risk of CMM, with HR 0.44 (95% CI 0.26, 0.73) for consuming fish/seafood 1-2 days/week compared to less than 1 day/week after adjustment. Further analyses with multi-state model showed that fish/seafood consumption played a protective role in the transition from FCMD to CMM. CONCLUSIONS: Our study did not find a significant association of baseline EDI with CMM but showed that consuming more fish/seafood per week was associated with a lower risk of transition from FCMD to CMM in older British men.

Stroke risk in older British men: Comparing performance of stroke-specific and composite-CVD risk prediction tools.

Stroke risk is currently estimated as part of the composite risk of cardiovascular disease (CVD). We investigated if composite-CVD risk prediction tools QRISK3 and Pooled Cohort Equations-PCE, derived from middle-aged adults, are as good as stroke-specific Framingham Stroke Risk Profile-FSRP and QStroke for capturing the true risk of stroke in older adults. External validation for 10y stroke outcomes was performed in men (60-79y) of the British Regional Heart Study. Discrimination and calibration were assessed in separate validation samples (FSRP n = 3762, QStroke n = 3376, QRISK3 n = 2669 and PCE n = 3047) with/without adjustment for competing risks. Sensitivity/specificity were examined using observed and clinically recommended thresholds. Performance of FSRP, QStroke and QRISK3 was further compared head-to-head in 2441 men free of a range of CVD, including across age-groups. Observed 10y risk (/1000PY) ranged from 6.8 (hard strokes) to 11 (strokes/transient ischemic attacks). All tools discriminated weakly, C-indices 0.63-0.66. FSRP and QStroke overestimated risk at higher predicted probabilities. QRISK3 and PCE showed reasonable calibration overall with minor mis-estimations across the risk range. Performance worsened on adjusting for competing non-stroke deaths. However, in men without CVD, QRISK3 displayed relatively better calibration for stroke events, even after adjustment for competing deaths, including in oldest men. All tools displayed similar sensitivity (63-73 %) and specificity (52-54 %) using observed risks as cut-offs. When QRISK3 and PCE were evaluated using thresholds for CVD prevention, sensitivity for stroke events was 99 %, with false positive rate 97 % suggesting existing intervention thresholds may need to be re-examined to reflect age-related stroke burden.

The Relationship of Oral Health with Progression of Physical Frailty among Older Adults: A Longitudinal Study Composed of Two Cohorts of Older Adults from the United Kingdom and United States.

OBJECTIVE: To investigate the prospective associations between oral health and progression of physical frailty in older adults. DESIGN: Prospective analysis. SETTING AND PARTICIPANTS: Data are from the British Regional Heart Study (BRHS) comprising 2137 men aged 71 to 92 years from 24 British towns and the Health, Aging, and Body Composition (HABC) Study of 3075 men and women aged 70 to 79 years. METHODS: Oral health markers included denture use, tooth count, periodontal disease, self-rated oral health, dry mouth, and perceived difficulty eating. Physical frailty progression after ∼8 years follow-up was determined based on 2 scoring tools: the Fried frailty phenotype (for physical frailty) and the Gill index (for severe frailty). Logistic regression models were conducted to examine the associations between oral health markers and progression to frailty and severe frailty, adjusted for sociodemographic, behavioral, and health-related factors. RESULTS: After full adjustment, progression to frailty was associated with dentition [per each additional tooth, odds ratio (OR) 0.97; 95% CI: 0.95-1.00], <21 teeth with (OR 1.74; 95% CI: 1.02-2.96) or without denture use (OR 2.45; 95% CI 1.15-5.21), and symptoms of dry mouth (OR ≥1.8; 95% CI ≥ 1.06-3.10) in the BRHS cohort. In the HABC Study, progression to frailty was associated with dry mouth (OR 2.62; 95% CI 1.05-6.55), self-reported difficulty eating (OR 2.12; 95% CI 1.28-3.50) and ≥2 cumulative oral health problems (OR 2.29; 95% CI 1.17-4.50). Progression to severe frailty was associated with edentulism (OR 4.44; 95% CI 1.39-14.15) and <21 teeth without dentures after full adjustment. CONCLUSIONS AND IMPLICATIONS: These findings indicate that oral health problems, particularly tooth loss and dry mouth, in older adults are associated with progression to frailty in later life. Additional research is needed to determine if interventions aimed at maintaining (or improving) oral health can contribute to reducing the risk, and worsening, of physical frailty in older adults.

Association between oral health markers and decline in muscle strength and physical performance in later life: longitudinal analyses of two prospective cohorts from the UK and the USA.

BACKGROUND: Poor oral health could be associated with changes in musculoskeletal health over time. This aim of this study was to investigate the longitudinal relationship between oral health and decline in physical function in later life. METHODS: We did a prospective analysis of two cohorts of older adults (aged 70 years or older) including men from the British Regional Heart Study (BRHS; n=612), and men and women from the Health, Aging and Body Composition (Health ABC) Study (n=1572), followed up for about 8 years. Data were available for clinical or self-reported oral health measures, muscle (grip) strength, and physical performance (chair stand and gait speed). ANCOVA models were used to assess the association between oral health and follow-up physical function scores. Multivariate logistic regression models were used to examine the associations between oral health and decline in physical function over the follow-up period. In the BRHS, changes in oral health and physical function were also assessed. All models were adjusted for relevant sociodemographic, behavioural, and health-related factors. FINDINGS: In the BRHS, complete tooth loss and difficulty eating were associated with weaker grip strength at follow-up, and periodontal status was associated with decline in gait speed. In the Health ABC Study, complete tooth loss, poor self-rated oral health, and the presence of one oral health problem were associated with slower gait speed at follow-up. In both studies, dry mouth was associated with declines in physical function. In the BRHS, deterioration of dentition (tooth loss) over the follow-up period was associated with decline in chair stand speed (adjusted odds ratio 2·34 [95% CI 1·20-4·46]), as was deterioration in difficulty eating (2·41 [1·04-5·60]). INTERPRETATION: Oral health problems are associated with poorer physical function and greater decline in physical function in older adults, and could be an indicator of individuals at risk of reduced physical capacity and subsequent frailty and disability in later life. FUNDING: The Dunhill Medical Trust and the US National Institutes of Health-National Institute of Dental and Craniofacial Research.

Haematological variables and risk of future venous thromboembolism in the British Regional Heart Study on men. Combined D-dimer and APTT as a predictive test for thromboembolism?

We examined the associations between haematological and inflammatory variables with future venous thromboembolism (VTE), in 3494 men aged 60-79 years, with no previous history of VTE or myocardial infarction, who were not receiving oral anticoagulants. After a mean follow-up period of 18 years, there were 149 confirmed cases of fatal or non-fatal VTE (deep vein thrombosis and/or pulmonary embolism). Among classical cardiovascular risk factors, only obesity and cigarette smoking were associated with VTE risk. After adjustment for age, obesity and smoking, VTE risk was associated with coagulation factor VIII, factor IX, von Willebrand factor (VWF), activated partial thromboplastin time (APTT), and fibrin D-dimer. Hazard ratios (95% CI) for top to bottom quarters (bottom to top for APTT), were respectively 2.17 (1.37, 3.44), 2.15 (1.30, 3.53), 2.02 (1.27, 3.22), 2.43 (1.47, 4.02) and 3.62 (2.18, 6.08). The 11% of men with both the shortest APTT and highest D-dimer combined had a 5.02 (2.37, 10.62) higher risk of VTE. VTE risk was not associated with fibrinogen, factor VII or activated protein C resistance; full blood count variables or with inflammatory markers, plasma viscosity, C-reactive protein or interleukin-6. The combination of D-dimer and APTT merits evaluation as an adjunct to VTE risk prediction scores.

Associations between inflammation, coagulation, cardiac strain and injury, and subclinical vascular disease with frailty in older men: a cross-sectional study.

BACKGROUND: Inflammation, coagulation activation, endothelial dysfunction and subclinical vascular disease are cross-sectionally associated with frailty. Cardiac-specific biomarkers are less-well characterised. We assessed associations between these and frailty, in men with, and without, cardiovascular disease (CVD). METHODS: Cross-sectional analysis of 1096 men without, and 303 with, CVD, aged 71-92, from the British Regional Heart Study. Multinominal logistic regression was performed to examine the associations between frailty status (robust/pre-frail/frail) and, separately, C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), D-dimer, von Willebrand factor (vWF), high-sensitivity cardiac troponin-T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) (all natural log-transformed), and, in men without CVD, carotid intima-media thickness (CIMT), carotid-femoral pulse wave velocity (cfPWV), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), adjusted for age, renal function, BMI, social class, smoking, polypharmacy, cognition, multimorbidity and systolic blood pressure. Explanatory variables with p < 0.05 were carried forward into mutually-adjusted analysis. RESULTS: In men without CVD, higher CRP, IL-6, vWF, tPA, hs-cTnT, NT-proBNP, cfPWV, and lower DC were significantly associated with frailty; mutually-adjusted, log IL-6 (OR for frailty = 2.02, 95%CI 1.38-2.95), log hs-cTnT (OR = 1.95, 95%CI 1.24-3.05) and DC (OR = 0.92, 95%CI 0.86-0.99) retained associations. In men with CVD, higher CRP, IL-6, and hs-cTnT, but not vWF, tPA, NT-proBNP or D-dimer, were significantly associated with frailty; mutually-adjusted, log hs-cTnT (OR 3.82, 95%CI 1.84-7.95) retained a significant association. CONCLUSIONS: In older men, biomarkers of myocardial injury are associated with frailty. Inflammation is associated with frailty in men without CVD. Carotid artery stiffness is associated with frailty in men without CVD, independently of these biomarkers.

Oral health problems and risk of incident disability in two studies of older adults in the United Kingdom and the United States.

BACKGROUND: Preventing oral health problems can be crucial for maintaining physical independence in older adults. We aimed to examine the associations of a range of oral health problems with incidence of disability in older adults. METHODS: We used prospective data from the British Regional Health Study (BRHS) (N = 2147, 71-92 years), and the Health, Aging and Body Composition (HABC) study (USA) (N = 3075, 71-80 years). Oral health measures included tooth loss, periodontal disease, self-rated oral health, and self-reported dry mouth. Participants were followed for onset of disability over a follow-up period of 3 years. Onset of disability was assessed through new cases of mobility limitations, activities of daily living (ADL), and instrumental activities of daily living (IADL). Logistic regression was performed to calculate the odds of incident disability. RESULTS: In the BRHS, tooth loss was associated with greater odds of mobility limitations and ADL difficulties. Periodontal disease was associated with greater incidence of mobility limitations. Self-report of ≥3 dry mouth symptoms was associated with increased odds of incident mobility limitations and ADL difficulties (OR = 2.08, 95% CI 1.27-3.42; OR = 1.73, 95% CI 1.03-2.90). Fair/poor self-rated oral health was associated with greater incidence of IADL difficulties. In the HABC study, complete tooth loss was associated with greater incidence of mobility limitations (OR = 1.86, 95% CI 1.13-3.06), and fair/poor self-rated oral health was associated with increased odds of incident ADL difficulties (OR = 1.42, 95% CI 1.04-1.94). CONCLUSIONS: Oral health problems in older adults, particularly tooth loss, self-reported dry mouth and self-rated oral health were associated with greater incidence of disability. Poor oral health plays a potentially important role in the development of disability in older populations, which in turn is an essential part of quality of life and healthy aging.

Social relationships and the risk of incident heart failure: results from a prospective population-based study of older men.

AIMS: Limited social relationships, particularly in older adults, have been implicated as a risk factor for cardiovascular disease. However, little is known about the associations between poor social relationships and heart failure incidence. METHODS AND RESULTS: Prospective study of socially representative men aged 60-79 years drawn from general practices in 24 British towns and followed up for a maximum of 18 years. A total of 3698 participants with no previous diagnosis of heart failure were included. Information on social relationships was based on a combination of marital status, living circumstances, and social contacts with friends and family. These provided information on contact frequency, contact satisfaction, and a social relationship score (low to high) combining frequency and satisfaction with contact. Heart failure included both incidents non-fatal heart failure and death from heart failure. Among 3698 participants, 330 developed heart failure. Men with low compared to high frequency of contact with family and friends had an increased risk of incident heart failure [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.15-2.18]; this remained statistically significant after adjustment for social class, behavioural, and biological risk factors. Low compared to high scores for satisfaction with contacts was associated with increased risk of heart failure (adjusted HR = 1.54; 95% CI 1.14-2.07). Lower social relationship scores (combining frequency and satisfaction with contact) were associated with greater risk of incident heart failure (adjusted HR = 1.38, 95% CI 1.02-1.87). Marital status and living alone were not significantly associated with heart failure. CONCLUSION: Weaker social relationships appear to increase the risk of developing heart failure in older age. Further research is needed to investigate pathways underlying these associations and to test whether interventions to strengthen social relationships can reduce the risk of heart failure.

Vitamin D deficiency, impaired lung function and total and respiratory mortality in a cohort of older men: cross-sectional and prospective findings from The British Regional Heart Study.

OBJECTIVES: Vitamin D deficiency is associated with chronic obstructive pulmonary disease (COPD). We examined the cross-sectional association between 25-hydroxyvitamin D (25(OH)D) and lung function impairment and assessed whether vitamin D deficiency is related to long-term mortality in those with impaired lung function. DESIGN: Prospective study SETTING: General practices in the UK. PARTICIPANTS: 3575 men aged 60-79 years with no prevalent heart failure. OUTCOME MEASURES: Airway obstruction and mortality. The Global Initiative on Obstructive Lung diseases (GOLD) spirometry criteria was used to define airway obstruction. RESULTS: During the follow-up period of 20 years, there were 2327 deaths (114 COPD deaths). Vitamin D deficiency was defined as serum 25(OH)D levels<10 ng/mL; insufficiency as 25(OH)D 10-19 ng/mL; sufficient as 25(OH)D>20 ng/mL. In cross-sectional analysis, vitamin D deficiency was more prevalent in those with moderate COPD (FEV/FVC <70% and FEV1 50 to <80%; FEV1, forced expiratory volume in 1 s and FVC, forced vital capacity) and severe COPD (FEV/FVC <70% and FEV1 <50%) but not in those with mild COPD (FEV/FVC <70% and FEV1>80%) or restrictive lung disease (FEV1/FVC >70% and FVC <80%) compared with men with normal lung function . Vitamin D deficiency was associated with increased risk of total and respiratory mortality in both men with COPD and men with restrictive lung disease after adjustment for confounders and inflammation. The adjusted HRs (95% CI) for total mortality comparing levels of 25(OH)D<10 ng/mL to 25(OH)D>=20 ng/mL were 1.39 (1.10 to 1.75), 1.52 (1.17 to 1.98), 1.58 (1.17 to 2.14) and 1.39 (0.83 to 2.33) for those with no lung impairment, restrictive lung function, mild/moderate COPD and severe COPD, respectively. CONCLUSION: Men with COPD were more likely to be vitamin D deficient than those with normal lung function. Vitamin D deficiency is associated with increased all-cause mortality in older men with no lung impairment as well as in those with restrictive or obstructive lung impairment.

Oral health and all-cause, cardiovascular disease, and respiratory mortality in older people in the UK and USA.

Preventing deterioration of oral health in older age can be crucial for survival. We aimed to examine associations of oral health problems with all-cause, cardiovascular disease (CVD), and respiratory mortality in older people. We used cohort data from the British Regional Health Study (BRHS) (N = 2147, 71-92 years), and the Health, Aging and Body Composition (HABC) Study (USA) (N = 3075, 71-80 years). Follow-up was 9 years (BRHS) and 15 years (HABC Study). Oral health comprised tooth loss, periodontal disease, dry mouth, and self-rated oral health. Cox regression was performed for all-cause mortality, competing risks for CVD mortality, and accelerated failure time models for respiratory mortality. In the BRHS, tooth loss was associated with all-cause mortality (hazard ratio (HR) = 1.59, 95% CI 1.09, 2.31). In the HABC Study, tooth loss, dry mouth, and having ≥ 3 oral problems were associated with all-cause mortality; periodontal disease was associated with increased CVD mortality (subdistribution hazard ratio (SHR) = 1.49, 95% CI 1.01, 2.20); tooth loss, and accumulation of oral problems were associated with high respiratory mortality (tooth loss, time ratio (TR) = 0.73, 95% CI 0.54, 0.98). Findings suggest that poor oral health is associated with mortality. Results highlight the importance of improving oral health to lengthen survival in older age.

Subclinical cardiovascular disease and risk of incident frailty: The British Regional Heart Study.

BACKGROUND/OBJECTIVES: Subclinical cardiovascular disease (CVD) is cross-sectionally associated with frailty, but the relationship between subclinical CVD and incident frailty has not been reported. We aimed to assess this prospective association. DESIGN: Longitudinal analysis of data from the British Regional Heart Study, a prospective cohort study. PARTICIPANTS: 1057 men, aged 71-92 years, robust or pre-frail at baseline, and without a clinical diagnosis of CVD. MEASUREMENTS: Participants underwent baseline measurement of carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (CIMT), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), and had questionnaire-based frailty assessment after three years. Frailty status was based on the Fried phenotype. Multivariate logistic regressions examined associations between incident frailty and tertile of cfPWV, CIMT, DC, and ABPI group (<0.9, 0.9-1.4, ≥1.4). RESULTS: 865 men were examined and completed the 3 year follow-up questionnaire, of whom 78 became frail. Adjusted for age, prefrailty, body mass index, diabetes, smoking, atrial fibrillation, blood pressure, renal function, and incident CVD, higher CIMT was associated with greater odds of incident frailty (2nd tertile OR 1.62, 95% CI 0.78-3.35, 3rd tertile OR 2.61, 95% CI 1.30-5.23, p = 0.007, trend p = 0.006). cfPWV showed a weaker, non-significant association (2nd tertile OR 1.79, 95% CI 0.85-3.78, 3rd tertile OR 1.73, OR 0.81-3.72, p = 0.16, trend p = 0.20). There was no clear association between incident frailty and DC or ABPI. In subgroup analyses, CIMT was significantly associated with incident frailty in men ≥80 years (3rd tertile OR 6.99, 95%CI 1.42-34.5), but not in men aged 75-80 or < 75 years. CONCLUSION: Subclinical CVD, as measured by CIMT, is associated with greater risk of incident frailty in older men over three year follow-up, independent of the development of clinically-apparent stroke, heart failure, or myocardial infarction, and may be a modifiable risk factor for frailty. This association may be stronger in very old age.

Adult height and incidence of atrial fibrillation and heart failure in older men: The British Regional Heart Study.

AIMS: Taller stature has been associated with increased risk of atrial fibrillation (AF). AF and heart failure (HF) often co-occur but the association between height and risk of HF in older adults has not been well studied. We have examined the association between height and incident AF and incident HF in older adults. METHODS: Prospective study of 3346 men aged 60-79 years with no diagnosed HF, myocardial infarction or stroke at baseline (1998-2000) followed up for a mean period of 16 years, in whom there were 294 incident HF cases and 456 incident AF. Men were divided into 5 height groups: <168.2, 168.2-172.5, 172.6-176.9, 177.0-183.0 and >183.0 cms based on the 25th, 50th, 75th and 95th centiles distribution of height. RESULTS: CVD risk factors tended to decrease with increasing height but a positive association was seen between height and electrocardiographic QRS duration and incident AF. Both short stature (<168.2 cm) and tall stature (>183.0 cm) was associated with significantly increased risk of HF in age-adjusted analysis compared to those in the second height quartile [HR (95 %CI) = 1.62 (1.15, 2.26) and 2.04 (1.23, 3.39) respectively]. In short men the increased risk remained after adjustment for adverse CVD risk factors; in tall men the association was largely associated with AF and QRS duration. CONCLUSION: Tall stature is associated with significantly increased risk of AF leading to increased risk of HF. Short stature was associated with increased HF risk which was not explained by known adverse CVD risk factors.

Associations between inflammation, cardiovascular biomarkers and incident frailty: the British Regional Heart Study.

INTRODUCTION: cardiovascular disease (CVD) and chronic inflammation are implicated in the development of frailty. Longitudinal analyses of inflammatory markers, biomarkers of cardiac dysfunction and incidence of frailty are limited. METHODS: in the British Regional Heart Study, 1,225 robust or pre-frail men aged 71-92 years underwent a baseline examination, with questionnaire-based frailty assessment after 3 years. Frailty definitions were based on the Fried phenotype. Associations between incident frailty and biomarkers of cardiac dysfunction (high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP)) and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) were examined, by tertile, with the lowest as reference. RESULTS: follow-up data were available for 981 men. Ninety one became frail. Adjusted for age, pre-frailty, prevalent and incident CVD, comorbidity, polypharmacy and socioeconomic status, IL-6 (third tertile OR 2.36, 95% CI 1.07-5.17) and hs-cTnT (third tertile OR 2.24, 95% CI 1.03-4.90) were associated with increased odds of frailty. CRP (third tertile OR 1.83, 95% CI 0.97-4.08) and NT-proBNP (second tertile OR 0.48, 95% CI 0.23-1.01) showed no significant association with incident frailty. The top tertiles of CRP, IL-6, hscTnT and NT-proBNP were strongly associated with mortality prior to follow-up. CONCLUSION: IL-6 is associated with incident frailty, supporting the prevailing argument that inflammation is involved in the pathogenesis of frailty. Cardiomyocyte injury may be associated with frailty risk. Associations between elevated CRP and frailty cannot be fully discounted; NT-proBNP may have a non-linear relationship with incident frailty. CRP, IL-6, hs-cTnT and NT-proBNP are vulnerable to survivorship bias.

Frailty and incident heart failure in older men: the British Regional Heart Study.

OBJECTIVE: Frailty and heart failure (HF) are cross-sectionally associated. Published longitudinal data are very limited. We sought to investigate associations between frailty and incident HF. METHODS: Prospective study of 1722 men, examined at age 72-91 years. Scores based on the Fried phenotype, Gill index and a novel frailty score, based on the Health Ageing and Body Composition Battery, incorporating slow walking speed, low chair-stand time and subjective difficulty with balance, were calculated. Associations between these scores and incident HF were analysed with Cox proportional hazard modelling. RESULTS: 1445 men with frailty data and without prevalent HF were included. 99 developed HF (mean follow-up 6.1 years). Men scoring 3/3 on our novel frailty score had elevated risk of incident HF (HR 2.77, 95% CI 1.25 to 6.15), which persisted after adjustment for established risk factors and interleukin-6 (HR 3.14, 95% CI 1.35 to 7.31). This risk remained increased, although attenuated, after excluding HF events within 2 years of baseline (HR 2.05, 95% CI 0.61 to 6.92). The frailty phenotype showed a non-significant association with HF (age-adjusted HR 1.92, 95% CI 0.99 to 3.73), which was further attenuated after adjustment for prevalent coronary heart disease and Body mass index (HR 1.60, 95% CI 0.81 to 3.15). Gill-type scores were weakly associated with HF risk after these adjustments (HR 1.31, 95% CI 0.47 to 3.70). CONCLUSION: In these older men, the combination of slow walk speed, low sit-stand time and balance problems were associated with high risk of incident HF, independent of established risk factors and inflammatory markers. However, undiagnosed HF at baseline may still be a confounder. There is a differential association between aspects of the frailty phenotype and incident HF.

Inflammatory markers and incident heart failure in older men: the role of NT-proBNP.

Aim: To determine the relationship between baseline inflammation (CRP and IL-6) with natriuretic peptide (NP) activity (measured by NT-proBNP) and incident heart failure (HF) in older men. Methods & results: In the British Regional Heart Study, 3569 men without prevalent myocardial infarction or HF were followed for mean 16.3 years; 327 developed HF. Baseline CRP and IL-6 were significantly and positively associated with NT-proBNP. Those in the highest CRP and IL-6 quartiles had an elevated risk of HF after age and BMI adjustment (HR = 1.42 [1.01-1.98] and 1.71 [1.24-2.37], respectively), which markedly attenuated after NT-proBNP adjustment (HR = 1.15 [0.81-1.63] and 1.25 [0.89-1.75], respectively). Conclusion: NP activity is associated with pro-inflammatory biomarkers and may explain the link between inflammation and incident HF.

Lay abstract Inflammation describes the body's natural response to infections, injuries and toxins. Inflammation is a helpful response in the short term, but it is thought that long-lasting inflammation ­ for example, due to illnesses such as diabetes or obesity ­ may have harmful effects. Previous studies have found that people with higher levels of inflammatory molecules in the blood seem to be more likely to develop heart failure (HF) later on. The amount of fluid in the body is controlled, in part, by molecules in the blood known as 'natriuretic peptides' (NPs). People with HF have much higher levels of NPs in their blood, and these are used to help diagnose HF. There are suggestions that inflammation and natriuretic peptides are linked to one another. Using a sample of men aged 60­79 years, who did not have HF, we compared blood markers of inflammation and NPs at a baseline examination. Men with higher blood inflammatory markers tended to have higher blood NP levels. We then followed these men up for an average of 16.3 years. Men with higher blood inflammatory markers at baseline were more likely to develop HF, as expected, even after accounting for differences in age and BMI. However, when we accounted for NP levels at baseline, the increased risk of HF with inflammation disappeared. This suggests that NP activity is important in the relationship between inflammation and the risk of HF. Future studies should account for this when examining the link. It is possible that NPs or, more likely, whatever is driving their release, may explain why people with inflammation are more likely to get HF.