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1.
Lancet Glob Health ; 8(4): e580-e590, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32199124

RESUMO

BACKGROUND: Stroke is a leading cause of death and disability worldwide. Despite considerable improvements in diagnosis and treatment, little is known about the short-term and long-term prognosis after a first stroke in low-income and middle-income countries, including China. We aimed to assess the short-term and long-term risk of recurrent stroke and mortality after a first stroke for each of the major pathological stroke types. METHODS: This population-based cohort study included adults aged 35-74 years without disability who were recruited to the China Kadoorie Biobank (CKB). A baseline survey was conducted in ten geographical areas (five urban, five rural) in China, and participants had clinical measurements recorded. Participants were followed up by monitoring death registries and by electronic linkage to health registries and health insurance claims databases, with follow-up until Jan 1, 2017. Participants were excluded from analyses if they had a previous history of stroke, transient ischaemic attack, or ischaemic heart disease at baseline. All incidences of fatal and non-fatal stroke during the study period were recorded by type (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and unspecified type). Primary outcome measures were 28-day mortality, recurrent stroke, major vascular events (recurrent stroke, myocardial infarction, or vascular death), vascular mortality, and all-cause mortality. FINDINGS: Of 512 715 individuals in the CKB, 489 586 participants without previous ischaemic heart disease and stroke at recruitment were included, of whom 45 732 (42 073 [92%] confirmed by brain imaging) had a stroke during the study period. The mean age was 59·3 years (SD 9·8) for participants who had a stroke (54% women) and 50·8 years (10·3) for participants with no stroke (60% women). 36 588 (80%) of the incident cases of stroke were ischaemic stroke, 7440 (16%) were intracerebral haemorrhage, 702 (2%) were subarachnoid haemorrhage, and 1002 (2%) were an unspecified stroke type. 28-day mortality was 3% (95% CI 3-4) for ischaemic stroke, 47% (46-48)for intracerebral haemorrhage, 19% (17-22; 52% for rural areas and 32% for urban areas) subarachnoid haemorrhage, and 24% (22-27) for unspecified stroke. Among participants who survived stroke at 28 days, 41% (41-42) had recurrent stroke at 5 years (ischaemic stroke 41% [41-42], intracerebral haemorrhage 44% [42-46], subarachnoid haemorrhage 22% [18-27], unspecified stroke type 40% [35-44]) and mortality at 5 years was 17% ([17-18] ischaemic stroke 16% [15-16], intracerebral haemorrhage 28% [26-29], subarachnoid haemorrhage 16% [12-20], unspecified stroke type 15% [12-19]). After a first ischaemic stroke, 91% of recurrent strokes were also ischaemic stroke; after an intracerebral haemorrhage, 56% of recurrent strokes were intracerebral haemorrhage, and 41% of recurrent strokes were ischaemic stroke. INTERPRETATION: After a first stroke, the risk of recurrence or death within 5 years was high among this population of Chinese adults. Urgent improvements to secondary prevention of stroke in China are needed to reduce these risks. FUNDING: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, National Natural Science Foundation of China. COPYRIGHT: © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

4.
Nature ; 577(7789): 179-189, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31915397

RESUMO

A primary goal of human genetics is to identify DNA sequence variants that influence biomedical traits, particularly those related to the onset and progression of human disease. Over the past 25 years, progress in realizing this objective has been transformed by advances in technology, foundational genomic resources and analytical tools, and by access to vast amounts of genotype and phenotype data. Genetic discoveries have substantially improved our understanding of the mechanisms responsible for many rare and common diseases and driven development of novel preventative and therapeutic strategies. Medical innovation will increasingly focus on delivering care tailored to individual patterns of genetic predisposition.

6.
J Am Heart Assoc ; 8(15): e011919, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31364443

RESUMO

Background Lean body mass has been identified as a key determinant of left ventricular mass and wall thickness. However, the importance of lean body mass or other body-size measures as normative determinants of carotid intima-media thickness (cIMT), a widely used early indicator of atherosclerosis, has not been well established. Methods and Results Carotid artery ultrasound measurements of cIMT and carotid artery plaque burden (derived from plaque number and maximum size) and measurements of body size, including height, body mass index, weight, body fat proportion, and lean body mass ([1-body fat proportion]×weight), were recorded in 25 020 participants from 10 regions of China. Analyses were restricted to a healthy younger subset (n=6617) defined as never or long-term ex-regular smokers aged <60 years (mean age, 50) without previous ischemic heart disease, stroke, diabetes mellitus, or hypertension and with plasma non-high-density lipoprotein cholesterol <4 mmol/L. Among these 6617 participants, 86% were women (because most men smoked) and 9% had carotid artery plaque. In both women and men separately, lean body mass was strongly positively associated with cIMT, but was not associated with plaque burden: overall, each 10 kg higher lean body mass was associated with a 0.03 (95% CI, 0.03-0.04) mm higher cIMT (P=5×10-33). Fat mass, height, and other body-size measures were more weakly associated with cIMT. Conclusions The strong association of lean body mass with cIMT, but not with plaque burden, in healthy adults suggests a normative relationship rather than reflecting atherosclerotic pathology. Common mechanisms may underlie the associations of lean body mass with cIMT and with nonatherosclerotic vascular traits.

7.
Ann Intern Med ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31404923

RESUMO

Background: Some reports suggest that body mass index (BMI) is not strongly associated with mortality in Hispanic populations. Objective: To assess the causal relevance of adiposity to mortality in Mexican adults, avoiding reverse causality biases. Design: Prospective study. Setting: 2 Mexico City districts. Participants: 159 755 adults aged 35 years and older at recruitment, followed for up to 14 years. Participants with a hemoglobin A1c level of 7% or greater, diabetes, or other chronic diseases were excluded. Measurements: BMI, waist-to-hip ratio, waist circumference, and cause-specific mortality. Cox regression, adjusted for confounders, yielded mortality hazard ratios (HRs) after at least 5 years of follow-up and before age 75 years. Results: Among 115 400 participants aged 35 to <75 years at recruitment, mean BMI was 28.0 kg/m2 (SD, 4.1 kg/m2) in men and 29.6 kg/m2 (SD, 5.1 kg/m2) in women. The association of BMI at recruitment with all-cause mortality was J-shaped, with the minimum at 25 to <27.5 kg/m2. Above 25 kg/m2, each 5-kg/m2 increase in BMI was associated with a 30% increase in all-cause mortality (HR, 1.30 [95% CI, 1.24 to 1.36]). This association was stronger at ages 40 to <60 years (HR, 1.40 [CI, 1.30 to 1.49]) than at ages 60 to <75 years (HR, 1.24 [CI, 1.17 to 1.31]) but was not materially affected by sex, smoking, or other confounders. The associations of mortality with BMI and waist-to-hip ratio were similarly strong, and each was weakened only slightly by adjustment for the other. Waist circumference was strongly related to mortality and remained so even after adjustment for BMI and hip circumference. Limitations: Analyses were limited to mortality. Conclusion: General, and particularly abdominal, adiposity were strongly associated with mortality in this Mexican population. Primary Funding Source: Mexican Health Ministry, Mexican National Council of Science and Technology, Wellcome Trust, Medical Research Council, and Kidney Research UK.

8.
Circ Genom Precis Med ; 12(9): 386-396, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31461308

RESUMO

BACKGROUND: Physical inactivity and sedentary behavior are associated with higher risk of cardiovascular disease (CVD). Little is known about the relevance of circulating metabolites for these associations. METHODS: A nested case-control study within the prospective China Kadoorie Biobank included 3195 incident CVD cases (2057 occlusive CVD and 1138 intracerebral hemorrhage) and 1465 controls aged 30 to 79 years without prior CVD or statin use at baseline. Nuclear magnetic resonance spectroscopy was used to measure 225 metabolic markers and derived traits in baseline plasma samples. Linear regression was used to relate self-reported physical activity and sedentary leisure time to biomarkers, adjusting for potential confounders. These were contrasted with associations of biomarkers with occlusive CVD risk. RESULTS: Physical activity and sedentary leisure time were associated with >100 metabolic markers, with patterns of associations generally mirroring each other. Physical activity was inversely associated with very low and low-density and positively with large and very large HDL (high-density lipoprotein) particle concentrations. Physical activity was also inversely associated with alanine, glucose, lactate, acetoacetate, and the inflammatory marker glycoprotein acetyls. In general, associations of physical activity and sedentary leisure time with specific metabolic markers were directionally consistent with the associations of these metabolic markers with occlusive CVD risk. Overall, metabolic markers potentially explained ≈70% of the protective associations of physical activity and ≈50% of the positive associations of sedentary leisure time with occlusive CVD. CONCLUSIONS: Among Chinese adults, physical activity and sedentary behavior have opposing associations with a diverse range of circulating metabolites, which may partially explain their associations with CVD risk.

9.
Circulation ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31331193

RESUMO

BACKGROUND: Exploratory analyses of previous randomized trials generated a hypothesis that the clinical response to CETP inhibitor therapy differs by ADCY9 genotype, prompting the ongoing dal-GenE trial in individuals with a particular genetic profile. The randomized placebo-controlled REVEAL trial demonstrated the clinical efficacy of the CETP inhibitor anacetrapib among patients with pre-existing atherosclerotic vascular disease. In the present study, we have examined the impact of ADCY9 genotype on response to anacetrapib within the REVEAL trial. METHODS: Individuals with stable atherosclerotic vascular disease, who were treated with intensive atorvastatin therapy, received either anacetrapib 100 mg daily or matching placebo. Cox proportional hazards models, adjusted for the first 5 principal components of ancestry, were used to estimate the effects of allocation to anacetrapib on major vascular events (a composite of coronary death, myocardial infarction, coronary revascularization or presumed ischaemic stroke) and the interaction with ADCY9 rs1967309 genotype. RESULTS: Among 19,210 genotyped individuals of European ancestry, 2,504 (13.0%) had a first major vascular event during 4 years median follow-up: 1,216 (12.6%) among anacetrapib-allocated participants and 1,288 (13.4%) among placebo-allocated participants. Proportional reductions in the risk of major vascular events with anacetrapib did not differ significantly by ADCY9 genotype: HR = 0.92 (95% CI, 0.81-1.05) for GG; HR = 0.94 (95% CI, 0.84-1.06) for AG; and HR = 0.93 (95% CI, 0.76-1.13) for AA genotype carriers respectively; genotypic p for interaction = 0.96. Furthermore, there were no associations between ADCY9 genotype and the proportional reductions in the separate components of major vascular events, or meaningful differences in lipid response to anacetrapib. CONCLUSIONS: The REVEAL trial is the single largest study to date evaluating the ADCY9 pharmacogenetic interaction. It provides no support for the hypothesis that ADCY9 genotype is materially relevant to the clinical effects of the CETP inhibitor anacetrapib. The ongoing dal-GenE study will provide direct evidence as to whether there is any specific pharmacogenetic interaction with dalcetrapib. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov Unique Identifier: NCT01252953; URL: http://www.isrctn.com Unique Identifier: ISRCTN48678192; URL: https://www.clinicaltrialsregister.eu Unique Identifier: 2010-023467-18.

10.
JAMA Netw Open ; 2(5): e194873, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31150080

RESUMO

Importance: A better understanding of the role of atherosclerosis in the development of ischemic stroke subtypes could help to improve strategies for prevention of stroke worldwide. Objective: To assess the role of carotid atherosclerosis in the association between major cardiovascular risk factors and ischemic stroke subtypes. Design, Setting, and Participants: The prospective China Kadoorie Biobank cohort study was conducted in the general population of 5 urban and 5 rural areas in China, with a baseline survey obtained between June 2004 and July 2008. A random sample of 23 973 participants with no history of cardiovascular disease at enrollment who had carotid artery ultrasonographic measurements recorded at a resurvey from September 2013 to June 2014 were included. Data analysis was performed from July 1, 2016, to April 10, 2019. Exposures: Major cardiovascular risk factors (ie, blood pressure [BP], blood lipid levels, smoking, and diabetes). Main Outcomes and Measures: Carotid ultrasonographic measures of plaque burden (derived from number and maximum size of carotid artery plaques at resurvey) and first ischemic stroke during follow-up (n = 952), with subtyping (data release, August 2018) as lacunar (n = 263), probable large artery (n = 193), probable cardioembolic (n = 66), or unconfirmed (n = 430). Associations between cardiovascular risk factors, carotid plaque burden, and ischemic stroke subtypes were adjusted for age, sex, and geographic area. Results: The 23 973 participants in the study had a mean (SD) age of 50.6 (10.0) years, and 14 833 (61.9%) were women. Systolic BP had a stronger association (odds ratio [OR] per SD, 1.51; 95% CI, 1.42-1.61) than plaque burden (OR per SD, 1.34; 95% CI, 1.26-1.44) with ischemic stroke, and the associations of systolic BP with each subtype of ischemic stroke were modestly attenuated by adjustment for plaque burden. After adjustment for BP, plaque burden had a stronger association with probable large artery stroke (OR, 1.43; 95% CI, 1.24-1.63) than with lacunar stroke (OR, 1.25; 95% CI, 1.10-1.43) but was not associated with probable cardioembolic stroke (OR, 1.06; 95% CI, 0.83-1.36). Conclusions and Relevance: Although BP was an important risk factor for all ischemic stroke subtypes, carotid atherosclerosis was an important risk factor only for large artery and lacunar strokes, suggesting that drug treatments targeting atherosclerosis may reduce the risk of stroke subtypes to different extents.


Assuntos
Pressão Sanguínea/fisiologia , Doenças das Artérias Carótidas/patologia , Estenose das Carótidas/patologia , Acidente Vascular Cerebral/etiologia , Adulto , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Estenose das Carótidas/diagnóstico por imagem , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/epidemiologia , Ultrassonografia
11.
Lancet ; 393(10183): 1831-1842, 2019 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-30955975

RESUMO

BACKGROUND: Moderate alcohol intake has been associated with reduced cardiovascular risk in many studies, in comparison with abstinence or with heavier drinking. Studies in east Asia can help determine whether these associations are causal, since two common genetic variants greatly affect alcohol drinking patterns. We used these two variants to assess the relationships between cardiovascular risk and genotype-predicted mean alcohol intake in men, contrasting the findings in men with those in women (few of whom drink). METHODS: The prospective China Kadoorie Biobank enrolled 512 715 adults between June 25, 2004, and July 15, 2008, from ten areas of China, recording alcohol use and other characteristics. It followed them for about 10 years (until Jan 1, 2017), monitoring cardiovascular disease (including ischaemic stroke, intracerebral haemorrhage, and myocardial infarction) by linkage with morbidity and mortality registries and electronic hospital records. 161 498 participants were genotyped for two variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984. Adjusted Cox regression was used to obtain the relative risks associating disease incidence with self-reported drinking patterns (conventional epidemiology) or with genotype-predicted mean male alcohol intake (genetic epidemiology-ie, Mendelian randomisation), with stratification by study area to control for variation between areas in disease rates and in genotype-predicted intake. FINDINGS: 33% (69 897/210 205) of men reported drinking alcohol in most weeks, mainly as spirits, compared with only 2% (6245/302 510) of women. Among men, conventional epidemiology showed that self-reported alcohol intake had U-shaped associations with the incidence of ischaemic stroke (n=14 930), intracerebral haemorrhage (n=3496), and acute myocardial infarction (n=2958); men who reported drinking about 100 g of alcohol per week (one to two drinks per day) had lower risks of all three diseases than non-drinkers or heavier drinkers. In contrast, although genotype-predicted mean male alcohol intake varied widely (from 4 to 256 g per week-ie, near zero to about four drinks per day), it did not have any U-shaped associations with risk. For stroke, genotype-predicted mean alcohol intake had a continuously positive log-linear association with risk, which was stronger for intracerebral haemorrhage (relative risk [RR] per 280 g per week 1·58, 95% CI 1·36-1·84, p<0·0001) than for ischaemic stroke (1·27, 1·13-1·43, p=0·0001). For myocardial infarction, however, genotype-predicted mean alcohol intake was not significantly associated with risk (RR per 280 g per week 0·96, 95% CI 0·78-1·18, p=0·69). Usual alcohol intake in current drinkers and genotype-predicted alcohol intake in all men had similarly strong positive associations with systolic blood pressure (each p<0·0001). Among women, few drank and the studied genotypes did not predict high mean alcohol intake and were not positively associated with blood pressure, stroke, or myocardial infarction. INTERPRETATION: Genetic epidemiology shows that the apparently protective effects of moderate alcohol intake against stroke are largely non-causal. Alcohol consumption uniformly increases blood pressure and stroke risk, and appears in this one study to have little net effect on the risk of myocardial infarction. FUNDING: Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, National Natural Science Foundation of China, British Heart Foundation, Cancer Research UK, GlaxoSmithKline, Medical Research Council, and Wellcome Trust.


Assuntos
Álcool Desidrogenase/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , Doenças Cardiovasculares/genética , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Aldeído-Desidrogenase Mitocondrial/metabolismo , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Hemorragia Cerebral/epidemiologia , China/epidemiologia , Extremo Oriente/epidemiologia , Feminino , Genótipo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia
12.
Kidney Int ; 96(1): 170-179, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31005271

RESUMO

Statin-based treatments reduce cardiovascular disease (CVD) risk in patients with non-dialysis chronic kidney disease (CKD), but it is unclear which regimen is the most cost-effective. We used the Study of Heart and Renal Protection (SHARP) CKD-CVD policy model to evaluate the effect of statins and ezetimibe on quality-adjusted life years (QALYs) and health care costs in the United States (US) and the United Kingdom (UK). Net costs below $100,000/QALY (US) or £20,000/QALY (UK) were considered cost-effective. We investigated statin regimens with or without ezetimibe 10 mg. Treatment effects on cardiovascular risk were estimated per 1-mmol/L reduction in low-density lipoprotein (LDL) cholesterol as reported in the Cholesterol Treatment Trialists' Collaboration meta-analysis, and reductions in LDL cholesterol were estimated for each statin/ezetimibe regimen. In the US, atorvastatin 40 mg ($0.103/day as of January 2019) increased life expectancy by 0.23 to 0.31 QALYs in non-dialysis patients with stages 3B to 5 CKD, at a net cost of $20,300 to $78,200/QALY. Adding ezetimibe 10 mg ($0.203/day) increased life expectancy by an additional 0.05 to 0.07 QALYs, at a net cost of $43,600 to $91,500/QALY. The cost-effectiveness findings and policy implications in the UK were similar. In summary, in patients with non-dialysis-dependent CKD, the evidence suggests that statin/ezetimibe combination therapy is a cost-effective treatment to reduce the risk of CVD.

13.
JAMA Netw Open ; 2(3): e190223, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30821829

RESUMO

Importance: Acquisition of reliable randomized clinical trial evidence of the effects of cardiovascular interventions on cognitive decline is a priority. Objectives: To estimate the association of cognitive aging with the avoidance of vascular events in cardiovascular intervention trials and understand whether reports of nonsignificant results exclude worthwhile benefit. Design, Setting, and Participants: This secondary analysis of 3 randomized clinical trials in participants with preexisting occlusive vascular disease or diabetes included survivors to final in-trial follow-up in the Heart Protection Study (HPS), Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), and Treatment of HDL (High-Density Lipoprotein) to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trials of lipid modification for prevention of cardiovascular events. Data were collected from February 1994 through January 2013 and analyzed from January 2015 through December 2018. Exposures: Incident vascular events and diabetes and statin therapy. Main Outcomes and Measures: Cognitive function was assessed at the end of a mean (SD) of 4.9 (1.5) years of follow-up using a 14-item verbal test. Associations of the incidence of vascular events and new-onset diabetes during the trials, with cognitive function at final in-trial follow-up were estimated and expressed as years of cognitive aging (using the association of the score with age >60 years). The benefit on cognitive aging mediated through the effects of lowering low-density lipoprotein cholesterol levels on events was estimated by applying these findings to nonfatal event differences observed with statin therapy in the HPS trial. Results: Among 45 029 participants undergoing cognitive assessment, mean (SD) age was 67.9 (8.0) years; 80.7% were men. Incident stroke (n = 1197) was associated with 7.1 (95% CI, 5.7-8.5) years of cognitive aging; incident transient ischemic attack, myocardial infarction, heart failure, and new-onset diabetes were associated with 1 to 2 years of cognitive aging. In HPS, randomization to statin therapy for 5 years resulted in 2.0% of survivors avoiding a nonfatal stroke or transient ischemic attack and 2.4% avoiding a nonfatal cardiac event, which yielded an expected reduction in cognitive aging of 0.15 (95% CI, 0.11-0.19) years. With 15 926 participants undergoing cognitive assessment, HPS had 80% power to detect a 1-year (ie, 20% during the 5 years) difference in cognitive aging. Conclusions and Relevance: The expected cognitive benefits of the effects of preventive therapies on cardiovascular events during even the largest randomized clinical trials may have been too small to be detectable. Hence, nonsignificant findings may not provide good evidence of a lack of worthwhile benefit on cognitive function with prolonged use of such therapies. Trial Registration: isrctn.com and ClinicalTrials.gov Identifiers: ISRCTN48489393, ISRCTN74348595, and NCT00461630.


Assuntos
Cognição/efeitos dos fármacos , Envelhecimento Cognitivo , Diabetes Mellitus/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Idoso , Feminino , Avaliação Geriátrica/métodos , Humanos , Incidência , Testes de Inteligência , Masculino , Pessoa de Meia-Idade , Doenças Vasculares/complicações , Doenças Vasculares/epidemiologia
14.
Nat Med ; 25(4): 569-574, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30858617

RESUMO

Stroke is the second leading cause of death worldwide and accounts for >2 million deaths annually in China1,2. Ischemic stroke (IS) and intracerebral hemorrhage (ICH) account for an equal number of deaths in China, despite a fourfold greater incidence of IS1,2. Stroke incidence and ICH proportion are higher in China than in Western populations3-5, despite having a lower mean low-density lipoprotein cholesterol (LDL-C) concentration. Observational studies reported weaker positive associations of LDL-C with IS than with coronary heart disease (CHD)6,7, but LDL-C-lowering trials demonstrated similar risk reductions for IS and CHD8-10. Mendelian randomization studies of LDL-C and IS have reported conflicting results11-13, and concerns about the excess risks of ICH associated with lowering LDL-C14,15 may have prevented the more widespread use of statins in China. We examined the associations of biochemically measured lipids with stroke in a nested case-control study in the China Kadoorie Biobank (CKB) and compared the risks for both stroke types associated with equivalent differences in LDL-C in Mendelian randomization analyses. The results demonstrated positive associations of LDL-C with IS and equally strong inverse associations with ICH, which were confirmed by genetic analyses and LDL-C-lowering trials. Lowering LDL-C is still likely to have net benefit for the prevention of overall stroke and cardiovascular disease in China.


Assuntos
Grupo com Ancestrais do Continente Asiático , Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Hemorragia Cerebral/sangue , Hemorragia Cerebral/epidemiologia , Lipídeos/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Fatores de Risco , Triglicerídeos/sangue
15.
Eur Heart J ; 40(14): 1158-1166, 2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-28531320
18.
N Engl J Med ; 379(16): 1529-1539, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30146931

RESUMO

BACKGROUND: Diabetes mellitus is associated with an increased risk of cardiovascular events. Aspirin use reduces the risk of occlusive vascular events but increases the risk of bleeding; the balance of benefits and hazards for the prevention of first cardiovascular events in patients with diabetes is unclear. METHODS: We randomly assigned adults who had diabetes but no evident cardiovascular disease to receive aspirin at a dose of 100 mg daily or matching placebo. The primary efficacy outcome was the first serious vascular event (i.e., myocardial infarction, stroke or transient ischemic attack, or death from any vascular cause, excluding any confirmed intracranial hemorrhage). The primary safety outcome was the first major bleeding event (i.e., intracranial hemorrhage, sight-threatening bleeding event in the eye, gastrointestinal bleeding, or other serious bleeding). Secondary outcomes included gastrointestinal tract cancer. RESULTS: A total of 15,480 participants underwent randomization. During a mean follow-up of 7.4 years, serious vascular events occurred in a significantly lower percentage of participants in the aspirin group than in the placebo group (658 participants [8.5%] vs. 743 [9.6%]; rate ratio, 0.88; 95% confidence interval [CI], 0.79 to 0.97; P=0.01). In contrast, major bleeding events occurred in 314 participants (4.1%) in the aspirin group, as compared with 245 (3.2%) in the placebo group (rate ratio, 1.29; 95% CI, 1.09 to 1.52; P=0.003), with most of the excess being gastrointestinal bleeding and other extracranial bleeding. There was no significant difference between the aspirin group and the placebo group in the incidence of gastrointestinal tract cancer (157 participants [2.0%] and 158 [2.0%], respectively) or all cancers (897 [11.6%] and 887 [11.5%]); long-term follow-up for these outcomes is planned. CONCLUSIONS: Aspirin use prevented serious vascular events in persons who had diabetes and no evident cardiovascular disease at trial entry, but it also caused major bleeding events. The absolute benefits were largely counterbalanced by the bleeding hazard. (Funded by the British Heart Foundation and others; ASCEND Current Controlled Trials number, ISRCTN60635500 ; ClinicalTrials.gov number, NCT00135226 .).


Assuntos
Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Hemorragia/induzido quimicamente , Inibidores da Agregação de Plaquetas/uso terapêutico , Prevenção Primária , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Complicações do Diabetes/epidemiologia , Feminino , Seguimentos , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Distribuição de Poisson , Fatores de Risco
19.
N Engl J Med ; 379(16): 1540-1550, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30146932

RESUMO

BACKGROUND: Increased intake of n-3 fatty acids has been associated with a reduced risk of cardiovascular disease in observational studies, but this finding has not been confirmed in randomized trials. It remains unclear whether n-3 (also called omega-3) fatty acid supplementation has cardiovascular benefit in patients with diabetes mellitus. METHODS: We randomly assigned 15,480 patients with diabetes but without evidence of atherosclerotic cardiovascular disease to receive 1-g capsules containing either n-3 fatty acids (fatty acid group) or matching placebo (olive oil) daily. The primary outcome was a first serious vascular event (i.e., nonfatal myocardial infarction or stroke, transient ischemic attack, or vascular death, excluding confirmed intracranial hemorrhage). The secondary outcome was a first serious vascular event or any arterial revascularization. RESULTS: During a mean follow-up of 7.4 years (adherence rate, 76%), a serious vascular event occurred in 689 patients (8.9%) in the fatty acid group and in 712 (9.2%) in the placebo group (rate ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.55). The composite outcome of a serious vascular event or revascularization occurred in 882 patients (11.4%) and 887 patients (11.5%), respectively (rate ratio, 1.00; 95% CI, 0.91 to 1.09). Death from any cause occurred in 752 patients (9.7%) in the fatty acid group and in 788 (10.2%) in the placebo group (rate ratio, 0.95; 95% CI, 0.86 to 1.05). There were no significant between-group differences in the rates of nonfatal serious adverse events. CONCLUSIONS: Among patients with diabetes without evidence of cardiovascular disease, there was no significant difference in the risk of serious vascular events between those who were assigned to receive n-3 fatty acid supplementation and those who were assigned to receive placebo. (Funded by the British Heart Foundation and others; Current Controlled Trials number, ISRCTN60635500 ; ClinicalTrials.gov number, NCT00135226 .).


Assuntos
Doenças Cardiovasculares/prevenção & controle , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , Adulto , Idoso , Aspirina/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus/mortalidade , Suplementos Nutricionais , Ácidos Graxos Ômega-3/efeitos adversos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Resultado do Tratamento
20.
Lancet Glob Health ; 6(6): e630-e640, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29773119

RESUMO

BACKGROUND: China has high stroke rates despite the population being relatively lean. Uncertainty persists about the relevance of adiposity to risk of stroke types. We aimed to assess the associations of adiposity with incidence of stroke types and effect mediation by blood pressure in Chinese men and women. METHODS: The China Kadoorie Biobank enrolled 512 891 adults aged 30-79 years from ten areas (five urban and five rural) during 2004-08. During a median 9 years (IQR 8-10) of follow-up, 32 448 strokes (about 90% confirmed by neuroimaging) were recorded among 489 301 participants without previous cardiovascular disease. Cox regression analysis was used to produce adjusted hazard ratios (HRs) for ischaemic stroke (n=25 210) and intracerebral haemorrhage (n=5380) associated with adiposity. FINDINGS: Mean baseline body-mass index (BMI) was 23·6 kg/m2 (SD 3·2), and 331 723 (67·8%) participants had a BMI of less than 25 kg/m2. Throughout the range examined (mean 17·1 kg/m2 [SD 0·9] to 31·7 kg/m2 [2·0]), each 5 kg/m2 higher BMI was associated with 8·3 mm Hg (SE 0·04) higher systolic blood pressure. BMI was positively associated with ischaemic stroke, with an HR of 1·30 (95% CI 1·28-1·33 per 5 kg/m2 higher BMI), which was generally consistent with that predicted by equivalent differences in systolic blood pressure (1·25 [1·24-1·26]). The HR for intracerebral haemorrhage (1·11 [1·07-1·16] per 5 kg/m2 higher BMI) was less extreme, and much weaker than that predicted by the corresponding difference in systolic blood pressure (1·48 [1·46-1·50]). Other adiposity measures showed similar associations with stroke types. After adjustment for usual systolic blood pressure, the positive associations with ischaemic stroke were attenuated (1·05 [1·03-1·07] per 5 kg/m2 higher BMI); for intracerebral haemorrhage, they were reversed (0·73 [0·70-0·77]). High adiposity (BMI >23 kg/m2) accounted for 14·7% of total stroke (16·5% of ischaemic stroke and 6·7% of intracerebral haemorrhage). INTERPRETATION: In Chinese adults, adiposity was strongly positively associated with ischaemic stroke, chiefly through its effect on blood pressure. For intracerebral haemorrhage, leanness, either per se or through some other factor (or factors), might increase risk, offsetting the protective effects of lower blood pressure. FUNDING: UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, Chinese National Natural Science Foundation.


Assuntos
Adiposidade , Isquemia Encefálica/epidemiologia , Hemorragia Cerebral/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco
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