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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.
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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.
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BACKGROUND: Higher concentrations of cholesterol-containing low-density lipoprotein (LDL-C) increase the risk of cardiovascular disease (CVD). The association of LDL-C with non-CVD traits remains unclear, as are the possible independent contributions of other cholesterol-containing lipoproteins and apolipoproteins. METHODS: Nuclear magnetic resonance spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C), as well as low-density lipoprotein fractions, the apolipoproteins Apo-A1 and Apo-B, as well as total triglycerides (TG), remnant-cholesterol (Rem-Chol) and total cholesterol (TC). The causal effects of these exposures were assessed against 33 outcomes using univariable and multivariable Mendelian randomization (MR). RESULTS: The majority of cholesterol containing lipoproteins and apolipoproteins affect coronary heart disease (CHD), carotid intima-media thickness, carotid plaque, C-reactive protein (CRP) and blood pressure. Multivariable MR indicated that many of these effects act independently of HDL-C, LDL-C and TG, the most frequently measured lipid fractions. Higher concentrations of TG, VLDL-C, Rem-Chol and Apo-B increased heart failure (HF) risk; often independently of LDL-C, HDL-C or TG. Finally, a subset of these exposures associated with non-CVD traits such as Alzheimer's disease (AD: HDL-C, LDL-C, IDL-C, Apo-B), type 2 diabetes (T2DM: VLDL-C, IDL-C, LDL-C), and inflammatory bowel disease (IBD: LDL-C, IDL-C). CONCLUSIONS: The cholesterol content of a wide range of lipoprotein and apolipoproteins associate with measures of atherosclerosis, blood pressure, CRP, and CHD, with a subset affecting HF, T2DM, AD and IBD risk. Many of the observed effects appear to act independently of LDL-C, HDL-C, and TG, supporting the targeting of lipid fractions beyond LDL-C for disease prevention.
It is known that increases in the amount of certain fats and proteins in the blood can lead to heart attacks. These increases are also found in people with other diseases. Here, we looked at inherited differences in some fats and proteins in blood to explore whether these could be associated with various diseases. We found that some fats and proteins in blood were associated with heart disease (including heart failure), blood pressure, blockages in blood vessels, and to a lesser extent with diabetes, Alzheimer's disease, and inflammatory bowel disease. These findings suggest that changes to lipids and proteins in the blood might lead to various diseases, including some that are not normally associated with changes in the blood. Monitoring these changes could improve diagnosis and treatment of these diseases.
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BACKGROUND & AIMS: To investigate potential biases that exist in available epidemiological evidence resulting in negative associations or underestimation of cardiovascular (CV) risk associated with alcohol consumption. METHODS: UK Biobank involved baseline data collection from 22 assessment centres across the United Kingdom. The cohort consisted of 333 259 alcohol consumers and 21 710 never drinkers. Participants were followed up for a median 6.9 years capturing incident fatal and non-fatal CV events, ischemic heart disease and cerebrovascular disease. Alcohol intake was reported as grams/week. RESULTS: Using never drinkers as reference, alcohol from all drink types combined (hazard ratios ranging between 0.61 and 0.74), beer/cider (0.70-0.80) and spirits combined, and all wines combined (0.66-0.77) associated with a reduced risk for all outcome measures (all CV events, ischaemic heart disease, cerebrovascular disease). In continuous analysis, alcohol captured from all drink types combined (hazard ratio, 1.08, 95% confidence interval, 1.01-1.14), and beer/cider and spirits combined (1.24, 1.17-1.31) associated with an increased risk for overall CV events, however hazard ratios were stronger for beer/cider and spirits (P < 0.0001). Wine associated with a reduced risk for overall CV events (0.92, 0.86-0.98) and ischemic heart disease (0.75, 0.67-0.84). This negative relationship with overall CV events was lost after excluding ischemic heart disease events (1.00, 0.93-1.08), while the positive association of alcohol captured from beer/cider and spirits remained significant (1.30, 1.22-1.40). This positive association with overall CV events was present even when consuming less than 14 units per week. CONCLUSIONS: Avoiding potential biases prevents underestimation of cardiovascular risk and indicates that consuming up to 14 units per week also associated with increased CV risk in the general population.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos Induzidos por Álcool/epidemiologia , Doenças Cardiovasculares/epidemiologia , Idoso , Transtornos Induzidos por Álcool/etiologia , Viés , Bancos de Espécimes Biológicos , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Reino Unido/epidemiologiaRESUMO
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.
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Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/genética , Análise da Randomização Mendeliana , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença das Coronárias/sangue , Humanos , Proteínas de Membrana Transportadoras/genética , Pró-Proteína Convertase 9/genética , Triglicerídeos/sangueRESUMO
BACKGROUND: Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR). METHODS: In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions. FINDINGS: We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4·60 (4·06-5·22) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5·87 (5·23-6·59) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1·23 (1·18-1·27), for men versus women was 1·12 (1·08-1·16), and for Black individuals versus White individuals was 1·13 (1·04-1·24). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period. INTERPRETATION: A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care. FUNDING: The British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research.
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Registros Eletrônicos de Saúde , Sobrepeso , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Masculino , Sobrepeso/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
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.
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Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Doença das Coronárias/prevenção & controle , Amidas/uso terapêutico , Benzodiazepinas/uso terapêutico , Doenças Cardiovasculares/metabolismo , Proteínas de Transferência de Ésteres de Colesterol/genética , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Doença das Coronárias/metabolismo , Ésteres/uso terapêutico , Humanos , Análise da Randomização Mendeliana , Oxazolidinonas/uso terapêutico , Quinolinas/uso terapêutico , Compostos de Sulfidrila/uso terapêuticoRESUMO
BACKGROUND: Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD. METHODS: We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group. RESULTS: Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals. CONCLUSION: Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.
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Doenças Cardiovasculares , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Registros Eletrônicos de Saúde , Humanos , Sobrepeso/epidemiologia , Fatores de RiscoRESUMO
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.
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Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Lipoproteínas/sangue , Ressonância Magnética Nuclear Biomolecular , Triglicerídeos/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Reino UnidoRESUMO
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.
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Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Colesterol/metabolismo , Dieta/estatística & dados numéricos , Exercício Físico , Fumar/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Estudos de Coortes , Fatores de Risco de Doenças Cardíacas , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Acidente Vascular Cerebral/mortalidade , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Carboxymethyl lysine is an advanced glycation end product of interest as a potential biomarker of cardiovascular and other diseases. Available methods involve ELISA, with potential interference, or isotope dilution mass spectrometry (IDMS), with low-throughput sample preparation. METHODS: A high-throughput sample preparation method based on 96-well plates was developed. Protein-bound carboxymethyl lysine and lysine were quantified by IDMS using reversed phase chromatography coupled to a high-resolution accurate mass Orbitrap Exactive mass spectrometer. The carboxymethyl lysine concentration (normalized to lysine concentration) was measured in 1714 plasma samples from the British Regional Heart Study (BRHS). RESULTS: For carboxymethyl lysine, the lower limit of quantification (LLOQ) was estimated at 0.16 µM and the assay was linear between 0.25 and 10 µM. For lysine, the LLOQ was estimated at 3.79 mM, and the assay was linear between 2.5 and 100 mM. The intra-assay coefficient of variation was 17.2% for carboxymethyl lysine, 9.3% for lysine and 10.5% for normalized carboxymethyl lysine. The inter-assay coefficient of variation was 18.1% for carboxymethyl lysine, 14.8 for lysine and 16.2% for normalized carboxymethyl lysine. The median and inter-quartile range of all study samples in each batch were monitored. A mean carboxymethyl lysine concentration of 2.7 µM (IQR 2.0-3.2 µM, range 0.2-17.4 µM) and a mean normalized carboxymethyl lysine concentration of 69 µM/M lysine (IQR 54-76 µM/M, range 19-453 µM/M) were measured in the BRHS. CONCLUSION: This high-throughput sample preparation method makes it possible to analyse large cohorts required to determine the potential of carboxymethyl lysine as a biomarker.
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Análise Química do Sangue/métodos , Lisina/análogos & derivados , Espectrometria de Massas , Métodos Analíticos de Preparação de Amostras , Biomarcadores/sangue , Calibragem , Humanos , Limite de Detecção , Lisina/sangueRESUMO
OBJECTIVE: The aim of this work was to study the association of high-sensitivity troponin T (hsTnT) with incident heart failure (HF), and implications for its use in prediction models. METHODS AND RESULTS: In the British Regional Heart Study, 3852 men aged 60-79years without baseline HF (3165 without baseline chronic heart disease) were followed for a median of 12.6years, during which 295 incident cases of HF occurred (7.7%). A 1-SD increase in log-transformed hsTnT was associated with a higher risk of incident HF after adjusting for classic risk factors (hazard ratio [HR] 1.58, 95% confidence interval [CI] 1.42-1.77) and after additional adjustment for N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR 1.34, 95% CI 1.19-1.52). The strength of the association between hsTnT and incident HF did not differ by strata of other risk factors. An hsTnT concentration of <5ng/L had a sensitivity of 99.7% (95% CI 98.1%-99.9%) and a specificity of 3.4% (95% CI 2.8%-4.0%). A risk-prediction model including classic risk factors and NT-proBNP yielded a C-index of 0.791, but addition of hsTnT did not further improve prediction (Pâ¯=â¯.28). CONCLUSIONS: Elevated hsTnT is consistently associated with risk of HF in older men. HF occurred rarely over 12years when baseline hsTnT was below the limit of detection. hsTnT measurement, however, does not improve HF prediction in a model already containing NT-proBNP.
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Previsões , Insuficiência Cardíaca/sangue , Medição de Risco/métodos , Troponina T/sangue , Adulto , Idoso , Biomarcadores/sangue , Seguimentos , Insuficiência Cardíaca/epidemiologia , Humanos , Imunoensaio , Incidência , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Precursores de Proteínas , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: This study aims to examine the tracking and predictability of physical activity in old age from overall physical activity and participation in sport, recreational activity and walking in mid-life. DESIGN: Prospective population-based cohort study. SETTING: British Regional Heart Study participants recruited from primary care centres in the UK in 1978-1980. PARTICIPANTS AND OUTCOME MEASURES: Men (n=3413) self-reported their physical activity at baseline, 12, 16 and 20-year follow-ups and were categorised as inactive or active and having high or low participation in sport, walking and recreational activities. Tracking was assessed using kappa statistics and random effects models. Logistic regression estimated the odds of being active at 20-year follow-up according to physical activity participation in mid-life. RESULTS: Among 3413 men (mean age at baseline 48.6±5.4 years) with complete data, tracking of overall physical activity was moderate (kappa: 0.23-0.26). Tracking was higher for sports participation (kappa: 0.35-0.38) compared with recreational activity (kappa: 0.16-0.24) and walking (kappa: 0.11-0.15). Intraclass correlation coefficients demonstrated similar levels of stability and only marginally weakened after controlling for covariates. Compared with inactive men, being active at baseline was associated with greater odds of being active at 20-year follow-up (OR 2.7, 95% CI 2.4 to 3.2) after adjusting for sociodemographic, health and lifestyle variables. Playing sport in mid-life was more strongly associated with being active at 20-year follow-up than other domains, particularly when sport participation began earlier in life. CONCLUSION: Being physically active in mid-life increases the odds of being active in old age. Promoting physical activity in later life might be best achieved by promoting sport participation earlier in the life course.
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Envelhecimento/fisiologia , Exercício Físico , Esportes , Idoso , Feminino , Inquéritos Epidemiológicos , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Autorrelato , Fatores Socioeconômicos , Reino Unido , CaminhadaRESUMO
BACKGROUND: Epidemiological evidence proposes the direct involvement of the liver enzymes in atrial fibrillation. These relationships are controversial and mechanistically unclear. As part of the British Regional Heart Study, we investigated whether change in liver enzymes over time associates with atrial fibrillation in men initially free of this heart condition. MATERIALS AND METHODS: We prospectively investigated change (delta) in liver enzymes and new-onset atrial fibrillation in a representative sample of 1428 men aged 60-79 years. RESULTS: Mean follow-up was 12·3 years, after which 108 new atrial fibrillation cases were identified. The liver enzymes did not differ at baseline or follow-up, except for gamma-glutamyl transferase which was higher at follow-up in men who developed atrial fibrillation compared to those who did not (P < 0·0001). Change in GGT was greater in men who developed AF than those who did not (+6·12 vs. -2·60 U/L, P = 0·036). N-terminal pro-brain natriuretic peptide (baseline and follow-up, P < 0·0001) and total bilirubin (follow-up only, P < 0·0001) were also higher in men who developed atrial fibrillation while serum haemoglobin was similar at baseline and follow-up (P ≥ 0·74). Atrial fibrillation was associated with change in gamma-glutamyl transferase (OR, 1·18; 95% CI, 1·01-1·37) after multiple adjustments and exclusions. However, after adjusting for baseline (P = 0·088) or change (P = 0·40) in N-terminal pro-brain natriuretic peptide, the association between atrial fibrillation and change in gamma-glutamyl transferase was lost. CONCLUSION: The direct relationship between atrial fibrillation and liver enzymes is absent and depends, at least in part, on the progression of heart failure as captured by N-terminal pro-brain natriuretic peptide.
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Fibrilação Atrial/enzimologia , Idoso , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Aspartato Aminotransferases/metabolismo , Fibrilação Atrial/diagnóstico por imagem , Bilirrubina/metabolismo , Seguimentos , Insuficiência Cardíaca/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Estudos Prospectivos , gama-Glutamiltransferase/metabolismoRESUMO
Impaired kidney function, as measured by reduced estimated glomerular filtration rate (eGFR), has been associated with increased risk of coronary heart disease (CHD) in observational studies, but it is unclear whether this association is causal or the result of confounding or reverse causation. In this study we applied Mendelian randomisation analysis using 17 genetic variants previously associated with eGFR to investigate the causal role of kidney function on CHD. We used 13,145 participants from the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium and 194,427 participants from the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis plus Coronary Artery Disease (CARDIoGRAMplusC4D) consortium. We observed significant association of an unweighted gene score with CHD risk (odds ratio = 0.983 per additional eGFR-increasing allele, 95% CI = 0.970-0.996, p = 0.008). However, using weights calculated from UCLEB, the gene score was not associated with disease risk (p = 0.11). These conflicting results could be explained by a single SNP, rs653178, which was not associated with eGFR in the UCLEB sample, but has known pleiotropic effects that prevent us from drawing a causal conclusion. The observational association between low eGFR and increased CHD risk was not explained by potential confounders, and there was no evidence of reverse causation, therefore leaving the remaining unexplained association as an open question.
Assuntos
Doença das Coronárias/fisiopatologia , Taxa de Filtração Glomerular/genética , Análise da Randomização Mendeliana , Doença das Coronárias/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Rim/metabolismo , Rim/fisiopatologia , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
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.
Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Gerenciamento Clínico , Medição de Risco , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/terapia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: The endopeptidase matrix metalloproteinase-9 (MMP-9) is implicated in atherosclerotic plaque rupture. We investigate prospective associations between MMP-9 and MI or stroke in an older general population cohort, accounting for established and novel cardiovascular risk factors. METHODS: Baseline serum MMP-9 was measured in incident MI (n=368) and stroke (n=299) cases and two controls per case, 'nested' in prospective studies of 4252 men and 4286 women aged 60-79 years, sampled from General Practices in Britain in 1998-2000, with 7-year follow-up for fatal and non-fatal MI and stroke. RESULTS: Geometric mean MMP-9 was 528 ng/mL (IQR 397, 743) in MI cases compared to 501 ng/mL (IQR 370, 743) in controls, p=0.10. Participants in the top compared to bottom third of MMP-9 levels had an age-adjusted odds ratio for MI of 1.53 (95% CI 1.09, 2.13), which attenuated to 1.18 (95% CI 0.81, 1.70) after adjustment for established and novel cardiovascular risk factors. There was weak evidence that OR differed according to pre-existing CVD; the OR for MI in 187 participants with pre-existing CVD was 2.20 (1.04, 4.64) and 1.24 (0.84, 1.82) in 715 participants without (LR test for interaction p=0.06). Geometric mean MMP-9 levels were higher in stroke cases than controls; 522ng/mL (IQR 363, 673) vs 487 (IQR 393, 704), p=0.045; however adjustments similarly attenuated the associations. CONCLUSIONS: While serum MMP-9 is univariately associated with risk of MI and stroke, it is not a strong independent risk marker for either.
Assuntos
Metaloproteinase 9 da Matriz/metabolismo , Infarto do Miocárdio/metabolismo , Acidente Vascular Cerebral/enzimologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Aterosclerose/metabolismo , Estudos de Coortes , Medicina de Família e Comunidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Estudos Prospectivos , Valores de Referência , Risco , Fatores de RiscoRESUMO
OBJECTIVES: This study sought to better determine the link between leptin and coronary heart disease (CHD). BACKGROUND: Circulating leptin is considered a risk factor for CHD but larger studies are needed. METHODS: Leptin levels were measured in 550 men with fatal CHD or nonfatal myocardial infarction and in 1,184 controls nested within a prospective study of 5,661 British men and set in context with a meta-analysis. RESULTS: Baseline leptin correlated with body mass index (BMI), blood pressure, total cholesterol, triglyceride, and inflammatory markers; correlations persisted after BMI adjustment. The within-person consistency of leptin values over 4 years (correlation coefficient: 0.79; 95% confidence interval [CI]: 0.73 to 0.83) was higher than those of some established cardiovascular risk factors. In a comparison of individuals in the top third with those in the bottom third of baseline leptin, the age- and town-adjusted odds ratio for CHD was 1.25 (95% CI: 0.96 to 1.62), decreasing to 0.98 (95% CI: 0.72 to 1.34) after adjustment for BMI. A systematic review identified 7 prospective reports with heterogeneous findings (I(2) = 60%, 13% to 82%). The combined adjusted risk ratio across all studies was 1.44 (95% CI: 0.95 to 2.16) in a comparison of extreme thirds of leptin levels. The inconsistency between studies was partially explained by sample size, with combined estimates from studies involving >100 CHD cases (1.28, 95% CI: 0.80 to 2.04) being somewhat weaker than those from smaller studies (1.81, 95% CI: 0.76 to 4.31). CONCLUSIONS: Previous studies appear to have overestimated associations of leptin and CHD risk. Our results suggest a moderate association that is largely dependent on BMI.
Assuntos
Doença das Coronárias/sangue , Leptina/sangue , Pressão Sanguínea , Índice de Massa Corporal , Estudos de Casos e Controles , Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Distribuição Aleatória , Fatores de Risco , Triglicerídeos/sangueRESUMO
BACKGROUND: The relationship between coronary heart disease (CHD) incidence and death, and individual sociodemographic status is well established. Our aim was to examine whether neighbourhood deprivation scores predict CHD and death in older men, independently of individual sociodemographic status. METHODS: Prospective study of 5049 men, born between 1918 and 1939, recruited from 24 British towns encompassing 969 electoral wards, without documented evidence of previous major CHD when responding to a questionnaire in 1992, and followed up for incidence of major CHD and death. RESULTS: Four hundred and seventy-two new major CHD events (1.08% pa), and 1021 deaths (2.28% pa) occurred over an average of 9.75 years. When men were divided into fifths according to increasing neighbourhood deprivation score, CHD incidences (% pa) were 0.92, 0.89, 0.99, 1.33 and 1.29. When modelling continuous trends, the rate ratio for men in the top fifth compared with the bottom fifth was 1.55 (95% confidence interval 1.19-2.00) for CHD. This rate ratio was, however, no longer statistically significant [1.22 (95% confidence interval 0.92-1.61)] when effects of individual sociodemographic status measures (car ownership, housing, longest held occupation, marital status and social networks) were accounted for. CONCLUSION: Little evidence of an independent relationship of neighbourhood deprivation with CHD incidence was found once individual measures of sociodemographic status had been adjusted for.
Assuntos
Causas de Morte , Doença das Coronárias/mortalidade , Características de Residência , Classe Social , Adulto , Inglaterra/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Áreas de Pobreza , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: There is uncertainty about the association between circulating concentrations of adiponectin and coronary heart disease (CHD) risk. We report new data from a prospective study in the context of a meta-analysis of previously published prospective studies. METHODS AND RESULTS: We measured baseline adiponectin levels in stored serum samples of 589 men with fatal CHD or nonfatal myocardial infarction and in 1231 controls nested within a prospective study of 5661 men (aged 40 to 59 years) recruited during 1978-1980, as well as in paired samples obtained 4 years apart from 221 of these participants. Baseline adiponectin concentrations correlated (P < 0.0001) positively with HDL cholesterol (r = 0.33) and inversely with C-reactive protein (r = -0.11) and BMI (r = -0.21), and the year-to-year consistency of adiponectin values was comparable to those of blood pressure and total cholesterol levels. No significant difference between median adiponectin levels at baseline was observed between cases and controls (10.2 versus 10.8 microg/mL; P = 0.5), despite the fact that body mass index, HDL, and C-reactive protein were all significant predictors of events in this cohort. The odds ratio for CHD was 0.89 (95% CI, 0.67 to 1.18) in a comparison of men in the top third of adiponectin concentrations compared with those in the bottom third, similar to a meta-analysis (including the present study) of 7 prospective studies involving a total of 1318 CHD cases (odds ratio, 0.84 [95% CI, 0.70 to 1.01]). CONCLUSIONS: In contrast to the strong associations previously reported between adiponectin levels and risk of type 2 diabetes, any association with CHD risk is comparatively moderate and requires further investigation.