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.

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.

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.

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.

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.

Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics.

Drug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter the target's expression or function, as a tool to anticipate the effect of drug action on the same target. Here we apply MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets are further prioritized using independent replication, co-localization, protein expression profiles and data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with blood lipids (HDL-C, LDL-C and triglycerides), we robustly prioritize 30 targets that might elicit beneficial effects in the prevention or treatment of CHD, including NPC1L1 and PCSK9, the targets of drugs used in CHD prevention. We discuss how this approach can be generalized to other targets, disease biomarkers and endpoints to help prioritize and validate targets during the drug development process.

Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease.

Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of proprotein convertase subtilisin/kexin type 9 (PCSK9). We show that previous failures of CETP inhibitors are likely compound related, as illustrated by significant degrees of between-compound heterogeneity in effects on lipids, blood pressure, and clinical outcomes observed in trials. On-target CETP inhibition, assessed through Mendelian randomization, is expected to reduce the risk of CHD, heart failure, diabetes, and chronic kidney disease, while increasing the risk of age-related macular degeneration. In contrast, lower PCSK9 concentration is anticipated to decrease the risk of CHD, heart failure, atrial fibrillation, chronic kidney disease, multiple sclerosis, and stroke, while potentially increasing the risk of Alzheimer's disease and asthma. Due to distinct effects on lipoprotein metabolite profiles, joint inhibition of CETP and PCSK9 may provide added benefit. In conclusion, we provide genetic evidence that CETP is an effective target for CHD prevention but with a potential on-target adverse effect on age-related macular degeneration.

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.

Excessive Orthostatic Changes in Blood Pressure Are Associated With Incident Heart Failure in Older Men: A Prospective Analysis From the BRHS.

[Figure: see text].

Establishing reference intervals for triglyceride-containing lipoprotein subfraction metabolites measured using nuclear magnetic resonance spectroscopy in a UK population.

BACKGROUND: Nuclear magnetic resonance (NMR) spectroscopy allows triglycerides to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these subfractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 triglyceride-containing lipoprotein subfraction metabolites. METHODS: Lipoprotein subfractions using the Nightingale NMR platform were measured in 9073 participants from four cohort studies contributing to the UCL-Edinburgh-Bristol consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for a disease-free population, by sex and age group (<55, 55-65, >65 years), and in a subgroup population of participants with cardiovascular disease or type 2 diabetes. We also determined the distribution across body mass index and smoking status. RESULTS: The largest reference interval range was observed in the medium very-low density lipoprotein subclass (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among male and female participants, with the exception of triglyceride in high-density lipoprotein. Triglyceride subfraction concentrations in very-low density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and high-density lipoprotein subclasses increased with increasing age and increasing body mass index. Triglyceride subfraction concentrations were significantly higher in ever smokers compared to never smokers, among those with clinical chemistry measured total triglyceride greater than 1.7 mmol/L, and in those with cardiovascular disease, and type 2 diabetes as compared to disease-free subjects. CONCLUSION: This is the first study to establish reference interval ranges for 14 triglyceride-containing lipoprotein subfractions in samples from the general population measured using the nuclear magnetic resonance platform. The utility of nuclear magnetic resonance lipid measures may lead to greater insights for the role of triglyceride in cardiovascular disease, emphasizing the importance of appropriate reference interval ranges for future clinical decision making.

Vitamin D deficiency is associated with orthostatic hypotension in older men: a cross-sectional analysis from the British Regional Heart Study.

BACKGROUND: orthostatic hypotension (OH) that occurs within, or at, 1 minute of standing is associated with higher risk of falls, myocardial infarction, syncope and mortality, compared to OH that occurs after 1 minute of standing. Whether vitamin D deficiency increases the risk of OH is controversial. METHODS: this was a cross-sectional analysis of 3,620 older, community-dwelling men. Multinomial, multiple logistic regression models were used to calculate the risk of OH across categories of vitamin D status (deficient [<25 nmol/l], insufficient [≥25-<50 nmol/l] and sufficient [≥50 nmol/l]) and parathyroid hormone quintile. RESULTS: men with vitamin D deficiency were more likely to have OH that occurred within 1 minute of standing in univariate logistic regression (OR 1.88, 95% CI 1.40-2.53) and multinomial, multiple logistic regression (OR 1.51, 95% CI 1.06-2.15), compared to men with sufficient levels of vitamin D. Vitamin D insufficiency was not associated with the risk of OH. Elevated parathyroid hormone was not associated with risk of OH. CONCLUSION: the absence of an association between vitamin D insufficiency and risk of OH and the presence of an association between vitamin D deficiency and risk of OH suggest that there may be a threshold effect; it is only below a particular level of vitamin D that risk of OH is increased. In this cohort, the threshold was <25 nmol/l. Future work should investigate whether treating vitamin D deficiency can improve postural blood pressure or if preventing vitamin D deficiency reduces the incidence of OH.

Associations of the systolic and diastolic components of orthostatic hypotension with markers of cardiovascular risk in older men: A cross-sectional analysis from The British Regional Heart Study.

The mechanisms underlying the association between orthostatic hypotension (OH) and cardiovascular disease are unclear. We investigated whether OH is associated with circulating cardiovascular risk markers. This was a cross-sectional analysis of 3857 older, community-dwelling men. "Consensus OH" was defined as a sitting-to-standing decrease in systolic blood pressure ≥20 mm Hg and/or diastolic blood pressure ≥10 mm Hg that occurred within three minutes of standing. Multiple generalized linear regression and logistic models were used to examine the association between cardiovascular risk markers and OH. Consensus OH was present in 20.2%, consisting of isolated systolic OH in 12.6%, isolated diastolic OH in 4.6%, and combined systolic and diastolic OH in 3.0%. Concentration of von Willebrand factor, a marker of endothelial dysfunction, was positively associated with isolated systolic OH (OR 1.35, 95% CI 1.05-1.73) and combined systolic and diastolic OH (OR 2.27, 95% CI 1.35-3.83); high circulating phosphate concentration, which may reflect vascular calcification, was associated with isolated diastolic OH (OR 1.53, 95% CI 1.04-2.25) and combined systolic and diastolic OH (OR 2.12, 95% CI 1.31-3.44), high-sensitivity troponin T, a marker of myocardial injury, was positively associated with isolated diastolic OH (OR 1.69, 95% CI 1.07-2.65) and N-terminal pro-brain natriuretic peptide, a marker of cardiac stress, was positively associated with combined systolic and diastolic OH (OR 2.14, 95% CI 1.14-4.03). In conclusion, OH is associated with some cardiovascular risk markers implicated in endothelial dysfunction, vascular calcification, myocardial injury, and cardiac stress. Clinicians should consider assessing cardiovascular risk in patients with OH.

Cardiovascular Health and Stroke in Older British Men: Prospective Findings From the British Regional Heart Study.

BACKGROUND AND PURPOSE: Research exploring the utility of cardiovascular health (CVH) and its Life's Simple 7 (LS7) components (body mass index, blood pressure [BP], glucose, cholesterol, physical activity, smoking, and diet) for prevention of stroke in older adults is limited. In the British Regional Heart Study, we explored (1) prospective associations of LS7 metrics and composite CVH scores with, and their impact on, stroke in middle and older age; and (2) if change in CVH was associated with subsequent stroke. METHODS: Men without cardiovascular disease were followed from baseline recruitment (1978-1980), and again from re-examination 20 years later, for stroke over a median period of 20 years and 16 years, respectively. LS7 were measured at each time point except baseline diet. Cox models estimated hazard ratios (95% CI) of stroke for (1) ideal and intermediate versus poor levels of LS7; (2) composite CVH scores; and (3) 4 CVH trajectory groups (low-low, low-high, high-low, high-high) derived by dichotomising CVH scores from each time point across the median value. Population attributable fractions measured impact of LS7. RESULTS: At baseline (n=7274, mean age 50 years), healthier levels of BP, physical activity, and smoking were associated with reduced stroke risk. At 20-year follow-up (n=3798, mean age 69 years) only BP displayed an association. Hazard ratios for intermediate and ideal (versus poor) levels of BP 0.65 (0.52-0.81) and 0.40 (0.24-0.65) at baseline; and 0.84 (0.67-1.05) and 0.57 (0.36-0.90) at 20-year follow-up. With reference to low-low trajectory, the low-high trajectory was associated with 40% reduced risk, hazard ratio 0.60 (0.44-0.83). Associations of CVH scores weakened, and population attributable fractions of LS7 reduced, from middle to old age; population attributable fraction of nonideal BP from 53% to 39%. CONCLUSIONS: Except for BP, CVH is weakly associated with stroke at older ages. Prevention strategies for older adults should prioritize BP control but also enhance focus beyond traditional risk factors.

Vitamin D deficiency is associated with increased risk of postural hypotension in older men: a cross-sectional analysis from The British Regional Heart Study.

BACKGROUND: There is growing interest in the role of vitamin D in extra-skeletal health, including postural hypotension. Postural hypotension is found in 1 in 5 community-dwelling adults aged 60 years and above. It increases risk of falls, fractures, cardiovascular disease and all-cause mortality. Better understanding of the aetiology of postural hypotension may help yield more effective treatment options than those that are currently available. AIM: The aim of this study was to investigate the association between circulating vitamin D, parathyroid hormone and postural hypotension. METHOD: This was a cross-sectional analysis of 3620 community-dwelling men living in the UK (mean age 68.6 years; standard deviation 5.5 years). Vitamin D status (nmol/L) was categorised as sufficient (≥50), insufficient (≥25 - <50), or deficient (<25). Parathyroid hormone levels were categorised by quintiles. Postural hypotension was defined by consensus criteria as a decrease in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg that occurred within three minutes of standing. RESULTS: Compared to sufficient levels of vitamin D, vitamin D deficiency increased risk of postural hypotension that specifically occurred within one minute of standing (OR 1.51, 95% CI = 1.06 to 2.15) in multinomial, multiple logistic regression. Neither vitamin D insufficiency, nor elevated parathyroid hormone, were associated with postural hypotension. CONCLUSION: In this study, vitamin D deficiency was associated with increased risk of postural hypotension. Further research may help clarify whether treating vitamin D deficiency can reduce the degree of postural hypotension, or if preventing the progression to vitamin D deficiency can reduce the incidence of postural hypotension.

Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults.

AIMS: Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. METHODS: Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. RESULTS: The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. CONCLUSIONS: Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

Trajectories of physical activity from midlife to old age and associations with subsequent cardiovascular disease and all-cause mortality.

INTRODUCTION: It is well established that physical activity (PA) protects against mortality and morbidity, but how long-term patterns of PA are associated with mortality and cardiovascular disease (CVD) remains unclear. METHODS: 3231 men recruited to the British Regional Heart Study, a prospective cohort study, reported usual PA levels at baseline in 1978-1980 (aged 40-59 years) and at 12-year, 16-year and 20-year follow ups. Twenty-year trajectories of PA, spanning from 1978/1980 to 2000, were identified using group-based trajectory modelling. Men were subsequently followed up until 30 June 2016 for mortality through National Health Service central registers and for non-fatal CVD events through primary and secondary care records. Data analyses were conducted in 2019. RESULTS: Three PA trajectories were identified: low/decreasing (22.7%), light/stable (51.0%) and moderate/increasing (26.3%). Over a median follow-up of 16.4 years, there were 1735 deaths. Compared with the low/decreasing group, membership of the light/stable (HR 0.83, 95% CI 0.74 to 0.94) and moderate/increasing (HR 0.76, 95% CI 0.66 to 0.88) groups was associated with a lower risk of all-cause mortality. Similar associations were observed for CVD mortality, major coronary heart disease and all CVD events. Associations were only partially explained by a range of confounders. Sensitivity analyses suggested that survival benefits were largely driven by most recent/current PA. CONCLUSIONS: A dose-response relationship was observed, with higher levels of PA from midlife to old age associated with additional benefits. However, even fairly modest and sustained PA was protective and may be more achievable for the most inactive.

Chronic kidney disease, cardiovascular risk markers and total mortality in older men: cystatin C versus creatinine.

BACKGROUND: It remains uncertain whether cystatin C is a superior marker of renal function than creatinine in older adults. We have investigated the association between estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on creatinine (CKD-EPIcr) and cystatin C (CKD-EPIcys), and cardiovascular risk markers and mortality in older adults. METHODS: This is a cross-sectional and prospective study of 1639 British men aged 71-92 years followed up for an average of 5 years for mortality. Cox survival model and receiving operating characteristic analysis were used to assess the associations. RESULTS: The prevalence of chronic kidney disease (CKD) was similar using the two CKD-EPI equations, although cystatin C reclassified 43.9% of those with stage 3a CKD (eGFR 45-59 mL/min/1.732, moderate damage) to no CKD. However, CKD stages assessed using both CKD-EPIcr and CKD-EPIcys were significantly associated with vascular risk markers and with all-cause and cardiovascular disease mortality. In all men with CKD (eGFR <60 mL/min/1.732), the HRs (95% CI) for all-cause mortality after adjustment for cardiovascular risk factors compared with those with no CKD were 1.53 (1.20 to 1.96) and 1.74 (1.35 to 2.23) using CKD-EPIcr and CKD-EPIcys, respectively. Comparisons of the two CKD equations showed no significant difference in their predictive ability for mortality (difference in area under the curve p=0.46). CONCLUSION: Despite reclassification of CKD stages, assessment of CKD using CKD-EPIcys did not improve prediction of mortality in older British men >70 years. Our data do not support the routine use of CKD-EPIcys for identifying CKD in the elderly British male population.

Physical frailty in older men: prospective associations with diet quality and patterns.

BACKGROUND: increasing numbers of older adults are living with frailty and its adverse consequences. We investigated relationships between diet quality or patterns and incident physical frailty in older British men and whether any associations were influenced by inflammation. METHODS: prospective study of 945 men from the British Regional Heart Study aged 70-92 years with no prevalent frailty. Incident frailty was assessed by questionnaire after 3 years of follow-up. Frailty was defined as having at least three of: low grip strength, low physical activity, slow walking speed, unintentional weight loss and feeling of low energy, all based on self-report. The Healthy Diet Indicator (HDI) based on WHO dietary guidelines and the Elderly Dietary Index (EDI) based on a Mediterranean-style dietary intake were computed from questionnaire data and three dietary patterns were identified using principal components analysis: prudent, high fat/low fibre and high sugar. RESULTS: men in the highest EDI category and those who followed a prudent diet were less likely to become frail [top vs bottom category odds ratio (OR) (95% CI) 0.49 (0.30, 0.82) and 0.53 (0.30, 0.92) respectively] after adjustment for potential confounders including BMI and prevalent cardiovascular disease. No significant association was seen for the HDI. By contrast those who had a high fat low fibre diet pattern were more likely to become frail [OR (95% CI) 2.54 (1.46, 4.40)]. These associations were not mediated by C-reactive protein (marker of inflammation). CONCLUSIONS: the findings suggest adherence to a Mediterranean-style diet is associated with reduced risk of developing frailty in older people.