RESUMO
BACKGROUND: Stroke is a leading cause of mortality and permanent disability in China, with large and unexplained geographic variations in rates of different stroke types. Chronic hepatitis B virus infection is prevalent among Chinese adults and may play a role in stroke cause. METHODS: The prospective China Kadoorie Biobank included >500â 000 adults aged 30 to 79 years who were recruited from 10 (5 urban and 5 rural) geographically diverse areas of China from 2004 to 2008, with determination of hepatitis B surface antigen (HBsAg) positivity at baseline. During 11 years of follow-up, a total of 59â 117 incident stroke cases occurred, including 11â 318 intracerebral hemorrhage (ICH), 49â 971 ischemic stroke, 995 subarachnoid hemorrhage, and 3036 other/unspecified stroke. Cox regression models were used to estimate adjusted hazard ratios (HRs) for risk of stroke types associated with HBsAg positivity. In a subset of 17â 833 participants, liver enzymes and lipids levels were measured and compared by HBsAg status. RESULTS: Overall, 3.0% of participants were positive for HBsAg. HBsAg positivity was associated with an increased risk of ICH (adjusted HR, 1.29 [95% CI, 1.16-1.44]), similarly for fatal (n=5982; adjusted HR, 1.36 [95% CI, 1.16-1.59]) and nonfatal (n=5336; adjusted HR, 1.23 [95% CI, 1.06-1.44]) ICH. There were no significant associations of HBsAg positivity with risks of ischemic stroke (adjusted HR, 0.97 [95% CI, 0.92-1.03]), subarachnoid hemorrhage (adjusted HR, 0.87 [95% CI, 0.57-1.33]), or other/unspecified stroke (adjusted HR, 1.12 [95% CI, 0.89-1.42]). Compared with HBsAg-negative counterparts, HBsAg-positive individuals had lower lipid and albumin levels and higher liver enzyme levels. After adjustment for liver enzymes and albumin, the association with ICH from HBsAg positivity attenuated to 1.15 (0.90-1.48), suggesting possible mediation by abnormal liver function. CONCLUSIONS: Among Chinese adults, chronic hepatitis B virus infection is associated with an increased risk of ICH but not other stroke types, which may be mediated through liver dysfunction and altered lipid metabolism.
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Hemorragia Cerebral , Acidente Vascular Cerebral Hemorrágico , Hepatite B Crônica , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Albuminas , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/complicações , População do Leste Asiático , Acidente Vascular Cerebral Hemorrágico/epidemiologia , Acidente Vascular Cerebral Hemorrágico/etiologia , Antígenos de Superfície da Hepatite B , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , AVC Isquêmico/complicações , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/complicações , Hemorragia Subaracnóidea/complicaçõesRESUMO
BACKGROUND: Taller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke. METHODS AND FINDINGS: Height-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations. Two-sample MR approaches were used to examine the associations of genetically determined height with ischemic stroke and its subtypes (cardioembolic stroke, large-artery stroke, and small-vessel stroke) in multiple ancestries (the MEGASTROKE consortium, which included genome-wide studies of stroke and stroke subtypes: 60,341 ischemic stroke cases) supported by additional cases in individuals of white British ancestry (UK Biobank [UKB]: 4,055 cases) and Chinese ancestry (China Kadoorie Biobank [CKB]: 10,297 cases). The associations of genetically determined height with established cardiovascular and other risk factors were examined in 336,750 participants from UKB and 58,277 participants from CKB. In MEGASTROKE, genetically determined height was associated with a 4% lower risk (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.94, 0.99; p = 0.007) of ischemic stroke per 1 standard deviation (SD) taller height, but this masked a much stronger positive association of height with cardioembolic stroke (13% higher risk, OR 1.13 [95% CI 1.07, 1.19], p < 0.001) and stronger inverse associations with large-artery stroke (11% lower risk, OR 0.89 [0.84, 0.95], p < 0.001) and small-vessel stroke (13% lower risk, OR 0.87 [0.83, 0.92], p < 0.001). The findings in both UKB and CKB were directionally concordant with those observed in MEGASTROKE, but did not reach statistical significance: For presumed cardioembolic stroke, the ORs were 1.08 (95% CI 0.86, 1.35; p = 0.53) in UKB and 1.20 (0.77, 1.85; p = 0.43) in CKB; for other subtypes of ischemic stroke in UKB, the OR was 0.97 (95% CI 0.90, 1.05; p = 0.49); and for other nonlacunar stroke and lacunar stroke in CKB, the ORs were 0.89 (0.80, 1.00; p = 0.06) and 0.99 (0.88, 1.12; p = 0.85), respectively. In addition, genetically determined height was also positively associated with atrial fibrillation (available only in UKB), and with lean body mass and lung function, and inversely associated with low-density lipoprotein (LDL) cholesterol in both British and Chinese ancestries. Limitations of this study include potential bias from assortative mating or pleiotropic effects of genetic variants and incomplete generalizability of genetic instruments to different populations. CONCLUSIONS: The findings provide support for a causal association of taller adult height with higher risk of cardioembolic stroke and lower risk of other ischemic stroke subtypes in diverse ancestries. Further research is needed to understand the shared biological and physical pathways underlying the associations between height and stroke risks, which could identify potential targets for treatments to prevent stroke.
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AVC Embólico , AVC Isquêmico , Acidente Vascular Cerebral , Adulto , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genéticaRESUMO
BACKGROUND: Alcohol consumption is an important risk factor for hepatic neoplastic and non-neoplastic diseases. Questions remain, however, about the relevance to disease risk of drinking patterns and alcohol tolerability, which differ appreciably between Chinese and Western populations. METHODS: The prospective China Kadoorie Biobank included 512,715 adults (41% men) aged 30-79 years recruited from ten areas during 2004-2008, recording alcohol intake, drinking patterns, and other characteristics. After median 10 years' follow-up, 2531 incident liver cancer, 2040 liver cirrhosis, 260 alcoholic liver disease (ALD), and 1262 non-alcoholic fatty liver disease (NAFLD) cases were recorded among 492,643 participants without prior cancer or chronic liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) relating alcohol intake and drinking patterns to each disease. RESULTS: Overall, 33% of men and 2% of women drank alcohol regularly (i.e. at least weekly) at baseline. Among male current regular drinkers, alcohol consumption showed positive dose-response associations with risks of several major chronic liver diseases, with HRs per 280 g/week (i.e. around four drinks/day) higher usual alcohol intake of 1.44 (95% CI 1.23-1.69) for liver cancer (n = 547), 1.83 (1.60-2.09) for liver cirrhosis (n = 388), 2.01 (1.77-2.28) for ALD (n = 200), 1.71 (1.35-2.16) for NAFLD (n = 198), and 1.52 (1.40-1.64) for total liver disease (n = 1775). The association with ALD appeared stronger among men reporting flushing (i.e., with low alcohol tolerance). After adjustment for the total amount of weekly alcohol consumption, daily drinkers had significantly increased risk of ALD (2.15, 1.40-3.31) compared with non-daily drinkers, and drinking without meals was associated with significantly greater risks of liver cancer (1.32, 1.01-1.72), liver cirrhosis (1.37, 1.02-1.85), and ALD (1.60, 1.09-2.33) compared with drinking with meals. Female current regular drinkers had significantly higher risk of ALD, but not other liver diseases, than female abstainers. CONCLUSIONS: In Chinese men, alcohol intake was associated with significantly increased risks of several major chronic liver diseases, and certain drinking patterns (e.g. drinking daily, drinking without meals) may further exacerbate the disease risks.
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Consumo de Bebidas Alcoólicas , Neoplasias Hepáticas , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , China/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: There is limited prospective evidence on the association of physical activity with hepatobiliary cancer subtypes and other major hepatobiliary diseases, especially in China. We aimed to quantify the associations with risk of these diseases. METHODS: The study population involved 460 937 participants of the prospective China Kadoorie Biobank aged 30-79 years from 10 diverse areas in China without history of cancer or hepatobiliary disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with self-reported total and domain-specific physical activity (occupational and non-occupational, ie, leisure time, household and commuting). RESULTS: During ~10 years of follow-up, 22 012 incident cases of hepatobiliary diseases were recorded. The overall mean (SD) total physical activity was 21.2 (13.9) metabolic equivalent of task (MET)-hours/day, with 62% from occupational activity. Total physical activity was inversely associated with hospitalised non-alcoholic fatty liver disease (HR comparing top vs bottom quintile: 0.62, 95% confidence interval (CI) 0.53 to 0.72), viral hepatitis (0.73, 95% CI 0.62 to 0.87), cirrhosis (0.76, 95% CI 0.66 to 0.88) and liver cancer (0.81, 95% CI 0.71 to 0.93), as well as gallstone disease (0.86, 95% CI 0.81 to 0.90), gallbladder cancer (0.51, 95% CI 0.32 to 0.80) and biliary tract cancer (0.55, 95% CI 0.38 to 0.78). The associations for occupational physical activity were similar to those for total physical activity, but for non-occupational physical activity they differed by disease subtype. For leisure-time physical activity, there was an inverse association with liver cancer and an inverse trend for gallstone disease (HR comparing ≥7.5 MET-hours/day with none: 0.83, 95% CI 0.75 to 0.91 and 0.82, 95% CI 0.66 to 1.01). CONCLUSION: Among Chinese adults, high total physical activity, particularly occupational physical activity, was inversely associated with risk of major hepatobiliary cancers and diseases, including non-alcoholic fatty liver disease, cirrhosis and certain types of cancer.
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Doenças do Sistema Digestório , Exercício Físico , Adulto , Idoso , China/epidemiologia , Doenças do Sistema Digestório/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
The prevalence of diabetes is increasing rapidly in China. However, evidence is limited about its effects on chronic liver diseases and liver cancer. We examined the associations of diabetes with chronic liver diseases and liver cancer and of random plasma glucose (RPG) with these liver diseases among participants without diabetes in Chinese adults and the possible interaction by hepatitis B virus (HBV) infection. The prospective China Kadoorie Biobank recruited 512,891 adults. During 10 years of follow-up, 2,568 liver cancer, 2,082 cirrhosis, 1,298 hospitalized nonalcoholic fatty liver disease (NAFLD), and 244 hospitalized alcoholic liver disease (ALD) cases were recorded among 503,993 participants without prior history of cancer or chronic liver diseases at baseline. Cox regression was used to estimate hazard ratios (HRs) for each disease by diabetes status (previously diagnosed or screen-detected) and, among those without previously diagnosed diabetes, by levels of RPG. Overall 5.8% of participants had diabetes at baseline. Compared to those without diabetes, individuals with diabetes had adjusted HRs of 1.49 (95% confidence interval 1.30-1.70) for liver cancer, 1.81 (1.57-2.09) for cirrhosis, 1.76 (1.47-2.16) for NAFLD, and 2.24 (1.42-3.54) for ALD. The excess risks decreased but remained elevated in those with longer duration. Among those without previously diagnosed diabetes, RPG was positively associated with liver diseases, with adjusted HRs per 1 mmol/L higher RPG of 1.04 (1.03-1.06) for liver cancer, 1.07 (1.05-1.09) for cirrhosis, 1.07 (1.05-1.10) for NAFLD, and 1.10 (1.05-1.15) for ALD. These associations did not differ by HBV infection. CONCLUSION: In Chinese adults, diabetes and higher blood glucose levels among those without known diabetes are associated with higher risks of liver cancer and major chronic liver diseases.
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Glicemia/análise , Diabetes Mellitus/epidemiologia , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Fatores Etários , Idoso , China/epidemiologia , Estudos de Coortes , Comorbidade , Diabetes Mellitus/sangue , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores Sexuais , Análise de SobrevidaRESUMO
BACKGROUND: Little prospective evidence exists about risk factors and prognosis of acute pancreatitis in China. We examined the associations of certain metabolic and lifestyle factors with risk of acute pancreatitis in Chinese adults. METHODS AND FINDINGS: The prospective China Kadoorie Biobank (CKB) recruited 512,891 adults aged 30 to 79 years from 5 urban and 5 rural areas between 25 June 2004 and 15 July 2008. During 9.2 years of follow-up (to 1 January 2015), 1,079 cases of acute pancreatitis were recorded. Cox regression was used to estimate adjusted hazard ratios (HRs) for acute pancreatitis associated with various metabolic and lifestyle factors among all or male (for smoking and alcohol drinking) participants. Overall, the mean waist circumference (WC) was 82.1 cm (SD 9.8) cm in men and 79.0 cm (SD 9.5) cm in women, 6% had diabetes, and 6% had gallbladder disease at baseline. WC was positively associated with risk of acute pancreatitis, with an adjusted HR of 1.35 (95% CI 1.27-1.43; p < 0.001) per 1-SD-higher WC. Individuals with diabetes or gallbladder disease had HRs of 1.34 (1.07-1.69; p = 0.01) and 2.42 (2.03-2.88; p < 0.001), respectively. Physical activity was inversely associated with risk of acute pancreatitis, with each 4 metabolic equivalent of task (MET) hours per day (MET-h/day) higher physical activity associated with an adjusted HR of 0.95 (0.91-0.99; p = 0.03). Compared with those without any metabolic risk factors (i.e., obesity, diabetes, gallbladder disease, and physical inactivity), the HRs of acute pancreatitis for those with 1, 2, or ≥3 risk factors were 1.61 (1.47-1.76), 2.36 (2.01-2.78), and 3.41 (2.46-4.72), respectively (p < 0.001). Among men, heavy alcohol drinkers (≥420 g/week) had an HR of 1.52 (1.11-2.09; p = 0.04, compared with abstainers), and current regular smokers had an HR of 1.45 (1.28-1.64; p = 0.02, compared with never smokers). Following a diagnosis of acute pancreatitis, there were higher risks of pancreatic cancer (HR = 8.26 [3.42-19.98]; p < 0.001; 13 pancreatic cancer cases) and death (1.53 [1.17-2.01]; p = 0.002; 89 deaths). Other diseases of the pancreas had similar risk factor profiles and prognosis to acute pancreatitis. The main study limitations are ascertainment of pancreatitis using hospital records and residual confounding. CONCLUSIONS: In this relatively lean Chinese population, several modifiable metabolic and lifestyle factors were associated with higher risks of acute pancreatitis, and individuals with acute pancreatitis had higher risks of pancreatic cancer and death.
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Consumo de Bebidas Alcoólicas/epidemiologia , Diabetes Mellitus/epidemiologia , Exercício Físico , Doenças da Vesícula Biliar/epidemiologia , Obesidade/epidemiologia , Pancreatite/epidemiologia , Fumar/epidemiologia , Doença Aguda , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Estilo de Vida , Masculino , Equivalente Metabólico , Pessoa de Meia-Idade , Mortalidade , Neoplasias Pancreáticas/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Circunferência da CinturaRESUMO
BACKGROUND: Despite the well-recognised health benefits of fresh fruit consumption, substantial uncertainties remain about its potential effects on incident diabetes and, among those with diabetes, on risks of death and major vascular complications. METHODS AND FINDINGS: Between June 2004 and July 2008, the nationwide China Kadoorie Biobank study recruited 0.5 million adults aged 30-79 (mean 51) y from ten diverse localities across China. During ~7 y of follow-up, 9,504 new diabetes cases were recorded among 482,591 participants without prevalent (previously diagnosed or screen-detected) diabetes at baseline, with an overall incidence rate of 2.8 per 1,000 person-years. Among 30,300 (5.9%) participants who had diabetes at baseline, 3,389 deaths occurred (overall mortality rate 16.5 per 1,000), along with 9,746 cases of macrovascular disease and 1,345 cases of microvascular disease. Cox regression yielded adjusted hazard ratios (HRs) associating each disease outcome with self-reported fresh fruit consumption, adjusting for potential confounders such as age, sex, region, socio-economic status, other lifestyle factors, body mass index, and family history of diabetes. Overall, 18.8% of participants reported consuming fresh fruit daily, and 6.4% never/rarely (non-consumers), with the proportion of non-consumers about three times higher in individuals with previously diagnosed diabetes (18.9%) than in those with screen-detected diabetes (6.7%) or no diabetes (6.0%). Among those without diabetes at baseline, higher fruit consumption was associated with significantly lower risk of developing diabetes (adjusted HR = 0.88 [95% CI 0.83-0.93] for daily versus non-consumers, p < 0.001, corresponding to a 0.2% difference in 5-y absolute risk), with a clear dose-response relationship. Among those with baseline diabetes, higher fruit consumption was associated with lower risks of all-cause mortality (adjusted HR = 0.83 [95% CI 0.74-0.93] per 100 g/d) and microvascular (0.72 [0.61-0.87]) and macrovascular (0.87 [0.82-0.93]) complications (p < 0.001), with similar HRs in individuals with previously diagnosed and screen-detected diabetes; estimated differences in 5-y absolute risk between daily and non-consumers were 1.9%, 1.1%, and 5.4%, respectively. The main limitation of this study was that, owing to its observational nature, we could not fully exclude the effects of residual confounding. CONCLUSION: In this large epidemiological study in Chinese adults, higher fresh fruit consumption was associated with significantly lower risk of diabetes and, among diabetic individuals, lower risks of death and development of major vascular complications.
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Diabetes Mellitus/epidemiologia , Angiopatias Diabéticas/epidemiologia , Comportamento Alimentar , Frutas , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores de RiscoRESUMO
Importance: In China, diabetes prevalence has increased substantially in recent decades, but there are no reliable estimates of the excess mortality currently associated with diabetes. Objectives: To assess the proportional excess mortality associated with diabetes and estimate the diabetes-related absolute excess mortality in rural and urban areas of China. Design, Setting, and Participants: A 7-year nationwide prospective study of 512â¯869 adults aged 30 to 79 years from 10 (5 rural and 5 urban) regions in China, who were recruited between June 2004 and July 2008 and were followed up until January 2014. Exposures: Diabetes (previously diagnosed or detected by screening) recorded at baseline. Main Outcomes and Measures: All-cause and cause-specific mortality, collected through established death registries. Cox regression was used to estimate adjusted mortality rate ratio (RR) comparing individuals with diabetes vs those without diabetes at baseline. Results: Among the 512â¯869 participants, the mean (SD) age was 51.5 (10.7) years, 59% (n = 302â¯618) were women, and 5.9% (n = 30â¯280) had diabetes (4.1% in rural areas, 8.1% in urban areas, 5.8% of men, 6.1% of women, 3.1% had been previously diagnosed, and 2.8% were detected by screening). During 3.64 million person-years of follow-up, there were 24â¯909 deaths, including 3384 among individuals with diabetes. Compared with adults without diabetes, individuals with diabetes had a significantly increased risk of all-cause mortality (1373 vs 646 deaths per 100â¯000; adjusted RR, 2.00 [95% CI, 1.93-2.08]), which was higher in rural areas than in urban areas (rural RR, 2.17 [95% CI, 2.07-2.29]; urban RR, 1.83 [95% CI, 1.73-1.94]). Presence of diabetes was associated with increased mortality from ischemic heart disease (3287 deaths; RR, 2.40 [95% CI, 2.19-2.63]), stroke (4444 deaths; RR, 1.98 [95% CI, 1.81-2.17]), chronic liver disease (481 deaths; RR, 2.32 [95% CI, 1.76-3.06]), infections (425 deaths; RR, 2.29 [95% CI, 1.76-2.99]), and cancer of the liver (1325 deaths; RR, 1.54 [95% CI, 1.28-1.86]), pancreas (357 deaths; RR, 1.84 [95% CI, 1.35-2.51]), female breast (217 deaths; RR, 1.84 [95% CI, 1.24-2.74]), and female reproductive system (210 deaths; RR, 1.81 [95% CI, 1.20-2.74]). For chronic kidney disease (365 deaths), the RR was higher in rural areas (18.69 [95% CI, 14.22-24.57]) than in urban areas (6.83 [95% CI, 4.73-9.88]). Among those with diabetes, 10% of all deaths (16% rural; 4% urban) were due to definite or probable diabetic ketoacidosis or coma (408 deaths). Conclusions and Relevance: Among adults in China, diabetes was associated with increased mortality from a range of cardiovascular and noncardiovascular diseases. Although diabetes was more common in urban areas, it was associated with greater excess mortality in rural areas.
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Diabetes Mellitus/mortalidade , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Neoplasias da Mama/mortalidade , Causas de Morte , China/epidemiologia , Feminino , Neoplasias dos Genitais Femininos/mortalidade , Humanos , Infecções/mortalidade , Hepatopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Pancreatopatias/mortalidade , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Insuficiência Renal Crônica/mortalidade , Distribuição por Sexo , Acidente Vascular Cerebral/mortalidadeRESUMO
Aims: The prevalence of atrial fibrillation (AF) is positively correlated with prior cardiovascular diseases (CVD) and CVD risk factors but is lower in Chinese than Europeans despite their higher burden of CVD. We examined the prevalence and prognosis of AF and other electrocardiogram (ECG) abnormalities in the China Kadoorie Biobank. Methods and results: A random sample of 25 239 adults (mean age 59.5 years, 62% women) had a 12-lead ECG recorded and interpreted using a Mortara VERITAS™ algorithm in 2013-14. Participants were followed up for 5 years for incident stroke, ischaemic heart disease, heart failure (HF), and all CVD, overall and by CHA2DS2-VASc scores, age, sex, and area. Overall, 1.2% had AF, 13.6% had left ventricular hypertrophy (LVH), and 28.1% had ischaemia (two-thirds of AF cases also had ischaemia or LVH). The prevalence of AF increased with age, prior CVD, and levels of CHA2DS2-VASc scores (0.5%, 1.3%, 2.1%, 2.9%, and 4.4% for scores <2, 2, 3, 4, and ≥5, respectively). Atrial fibrillation was associated with two-fold higher hazard ratios (HR) for CVD (2.15; 95% CI, 1.71-2.69) and stroke (1.88; 1.44-2.47) and a four-fold higher HR for HF (3.79; 2.21-6.49). The 5-year cumulative incidence of CVD was comparable for AF, prior CVD, and CHA2DS2-VASc scores ≥ 2 (36.7% vs. 36.2% vs. 37.7%, respectively) but was two-fold greater than for ischaemia (19.4%), LVH (18.0%), or normal ECG (14.1%), respectively. Conclusion: The findings highlight the importance of screening for AF together with estimation of CHA2DS2-VASc scores for prevention of CVD in Chinese adults.
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BACKGROUND: Infectious diseases remain a major global health concern, including in China, with an estimated >10 million cases of infectious disease in 2019. We describe the burden of site-specific infectious diseases among Chinese adults. METHODS: From 2004 to 2008, the prospective China Kadoorie Biobank enrolled 512,726 adults aged 30-79 years from 10 diverse areas (5 rural, 5 urban) of China. During the 12 years of follow-up, 101,673 participants were hospitalized for any infectious disease. Descriptive analyses examined standardized incidence, mortality and case fatality of infections. FINDINGS: The incidence of any infectious disease was 1856 per 100,000 person-years; respiratory tract infections (1069) were most common. The infectious disease mortality rate was 31.8 per 100,000 person-years (20.3 and 9.4 for respiratory and non-respiratory infections, respectively) and case fatality was 2.2% (2.6% and 1.6% for respiratory and non-respiratory infections, respectively). Infectious disease incidence and mortality rates were higher at older ages and in rural areas. There were no clear sex differences in infectious disease incidence rates, but mortality and case fatality rates were twice as high in men as in women. INTERPRETATION: Infectious diseases were common in Chinese adults. The observed burden of, and disparities in, site-specific infections can inform targeted prevention efforts. FUNDING: Kadoorie Foundation, Wellcome Trust, MRC, BHF, CR-UK, MoST, NNSF.
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AIMS: Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition. METHODS AND RESULTS: In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)]. Logistic regression gave estimated odds ratios (ORs) for PCSK9-GS associations with CVD and non-CVD outcomes, scaled to 1 SD lower LDL-C. PCSK9-GS was associated with lower risks of carotid plaque [n = 8340 cases; OR = 0.61 (95% confidence interval: 0.45-0.83); P = 0.0015], major occlusive vascular events [n = 15 752; 0.80 (0.67-0.95); P = 0.011], and ischaemic stroke [n = 11 467; 0.80 (0.66-0.98); P = 0.029]. However, PCSK9-GS was also associated with higher risk of hospitalization with chronic obstructive pulmonary disease [COPD: n = 6836; 1.38 (1.08-1.76); P = 0.0089] and with even higher risk of fatal exacerbations amongst individuals with pre-existing COPD [n = 730; 3.61 (1.71-7.60); P = 7.3 × 10-4]. We also replicated associations for a PCSK9 variant, reported in UK Biobank, with increased risks of acute upper respiratory tract infection (URTI) [pooled OR after meta-analysis of 1.87 (1.38-2.54); P = 5.4 × 10-5] and self-reported asthma [pooled OR of 1.17 (1.04-1.30); P = 0.0071]. There was no association of a polygenic LDL-C score with COPD hospitalization, COPD exacerbation, or URTI. CONCLUSION: The LDL-C-lowering PCSK9 genetic variants are associated with lower risk of subclinical and clinical atherosclerotic vascular disease but higher risks of respiratory diseases. Pharmacovigilance studies may be required to monitor patients treated with therapeutic PCSK9 inhibitors for exacerbations of respiratory diseases or respiratory tract infections. LAY SUMMARY: Genetic analyses of over 100 000 participants of the China Kadoorie Biobank, mimicking the effect of new drugs intended to reduce cholesterol by targeting the PCSK9 protein, have identified potential severe effects of lower PCSK9 activity in patients with existing respiratory disease.PCSK9 genetic variants that are associated with lower cholesterol and reduced rates of cardiovascular disease are also associated with increased risk of a range of respiratory diseases, including asthma, upper respiratory tract infections, and hospitalization with chronic obstructive pulmonary disease (COPD).These genetic variants are not associated with whether or not individuals have COPD; instead, they are specifically associated with an increase in the chance of those who already have COPD being hospitalized and even dying, suggesting that careful monitoring of such patients should be considered during development of and treatment with anti-PCSK9 medication.
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Predisposição Genética para Doença , Pró-Proteína Convertase 9 , Humanos , Pró-Proteína Convertase 9/genética , China/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Reino Unido/epidemiologia , Medição de Risco , Estudos Prospectivos , Fatores de Risco , LDL-Colesterol/sangue , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/epidemiologia , Biomarcadores/sangue , Fenótipo , População do Leste AsiáticoRESUMO
BACKGROUND: Reliable classification of ischemic stroke (IS) etiological subtypes is required in research and clinical practice, but the predictive properties of these subtypes in population studies with incomplete investigations are poorly understood. AIMS: To compare the prognosis of etiologically classified IS subtypes and use machine learning (ML) to classify incompletely investigated IS cases. METHODS: In a 9-year follow-up of a prospective study of 512,726 Chinese adults, 22,216 incident IS cases, confirmed by clinical adjudication of medical records, were assigned subtypes using a modified Causative Classification System for Ischemic Stroke (CCS) (large artery atherosclerosis (LAA), small artery occlusion (SAO), cardioaortic embolism (CE), or undetermined etiology) and classified by CCS as "evident," "probable," or "possible" IS cases. For incompletely investigated IS cases where CCS yielded an undetermined etiology, an ML model was developed to predict IS subtypes from baseline risk factors and screening for cardioaortic sources of embolism. The 5-year risks of subsequent stroke and all-cause mortality (measured using cumulative incidence functions and 1 minus Kaplan-Meier estimates, respectively) for the ML-predicted IS subtypes were compared with etiologically classified IS subtypes. RESULTS: Among 7443 IS subtypes with evident or probable etiology, 66% had SAO, 32% had LAA, and 2% had CE, but proportions of SAO-to-LAA cases varied by regions in China. CE had the highest rates of subsequent stroke and mortality (43.5% and 40.7%), followed by LAA (43.2% and 17.4%) and SAO (38.1% and 11.1%), respectively. ML provided classifications for cases with undetermined etiology and incomplete clinical data (24% of all IS cases; n = 5276), with area under the curves (AUC) of 0.99 (0.99-1.00) for CE, 0.67 (0.64-0.70) for LAA, and 0.70 (0.67-0.73) for SAO for unseen cases. ML-predicted IS subtypes yielded comparable subsequent stroke and all-cause mortality rates to the etiologically classified IS subtypes. CONCLUSION: This study highlighted substantial heterogeneity in prognosis of IS subtypes and utility of ML approaches for classification of IS cases with incomplete clinical investigations.
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Aterosclerose , Isquemia Encefálica , Embolia , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Adulto , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , AVC Isquêmico/complicações , Estudos Prospectivos , Seguimentos , População do Leste Asiático , Prognóstico , Fatores de Risco , Embolia/complicações , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologiaRESUMO
BACKGROUND: The relevance of folic acid for stroke prevention in low-folate populations such as in China is uncertain. Genetic studies of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which increases plasma homocysteine (tHcy) levels, could clarify the causal relevance of elevated tHcy levels for stroke, ischaemic heart disease (IHD) and other diseases in populations without folic acid fortification. METHODS: In the prospective China Kadoorie Biobank, 156â253 participants were genotyped for MTHFR and 12â240 developed a stroke during the 12-year follow-up. Logistic regression was used to estimate region-specific odds ratios (ORs) for total stroke and stroke types, IHD and other diseases comparing TT genotype for MTHFR C677T (two thymine alleles at position 677 of MTHFR C677T polymorphism) vs CC (two cytosine alleles) after adjustment for age and sex, and these were combined using inverse-variance weighting. RESULTS: Overall, 21% of participants had TT genotypes, but this varied from 5% to 41% across the 10 study regions. Individuals with TT genotypes had 13% (adjusted OR 1.13, 95% CI 1.09-1.17) higher risks of any stroke [with a 2-fold stronger association with intracerebral haemorrhage (1.24, 1.17-1.32) than for ischaemic stroke (1.11, 1.07-1.15)] than the reference CC genotype. In contrast, MTHFR C677T was unrelated to risk of IHD or any other non-vascular diseases, including cancer, diabetes and chronic obstructive lung disease. CONCLUSIONS: In Chinese adults, the MTHFR C677T polymorphism was associated with higher risks of stroke. The findings warrant corroboration by further trials of folic acid and implementation of mandatory folic acid fortification programmes for stroke prevention in low-folate populations.
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Isquemia Encefálica , Doença da Artéria Coronariana , Acidente Vascular Cerebral , Adulto , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Ácido Fólico , Genótipo , Homocisteína/genéticaRESUMO
Background: Widespread use of brain imaging in suspected stroke cases in Chinese adults has prompted the need for clinical adjudication studies of stroke types. We conducted a clinical adjudication study to assess the reporting and diagnostic accuracy of major stroke types. Methods: The prospective China Kadoorie Biobank recruited >512,000 adults (mean age 52 years, 59% women) from 10 urban and rural areas in China during 2004-2008, and recorded 45,859 first-ever incident stroke cases during an 11-year follow-up. Medical records were retrieved in â¼85%, and clinical details were recorded using a handheld computer for specialist physician adjudicators who applied conventional WHO clinical criteria for diagnosis of stroke. The positive predictive value (PPV) for reported and adjudicated stroke cases was examined for major stroke types (ischaemic stroke [IS], intracerebral haemorrhage [ICH], subarachnoid haemorrhage [SAH]), calendar year, area, and hospital type. Findings: Of 38,823 cases with retrieved medical records, the PPV for reported strokes was 91%. Among 29,952 adjudicated cases, the PPV for adjudicated cases was 81%, with higher PPV for ICH (n = 3391; 98%) and SAH (364; 98%) than for IS (20,473; 79%). Of 5504 cases with a verified IS diagnosis that was refuted on adjudication, 3763 (68%) had silent lacunar infarcts (LACI). The proportion of cases with silent LACI increased from 7.1% in 2004-2008 to 18.2% in 2016-2017. If cases with silent LACI were classified as IS, as advocated by new International Classification of Diseases (ICD-11) diagnostic criteria for stroke involving imaging and clinical rather than clinical criteria alone, the PPV increased to 93%. Interpretation: While the overall reporting and diagnostic accuracy of stroke types in Chinese adults is high, the recent implementation of new diagnostic criteria for IS has important implications for contemporary clinical practice and research on stroke in Chinese populations. Funding: Kadoorie Charitable Foundation, Hong Kong, China, UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), Chinese National Natural Science Foundation (91843302), and the National Key Research and Development Program of China (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904). British Heart Foundation, and UK Medical Research Council, and Cancer Research UK.
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BACKGROUND: Globally, the burden of obesity and associated nonalcoholic fatty liver disease (NAFLD) are rising, but little is known about the role that circulating metabolomic biomarkers play in mediating their association. OBJECTIVES: We aimed to examine the observational and genetic associations of adiposity with metabolomic biomarkers and the observational associations of metabolomic biomarkers with incident NAFLD. METHODS: A case-subcohort study within the prospective China Kadoorie Biobank included 176 NAFLD cases and 180 subcohort individuals and measured 1208 metabolites in stored baseline plasma using a Metabolon assay. In the subcohort the observational and genetic associations of BMI with biomarkers were assessed using linear regression, with adjustment for multiple testing. Cox regression was used to estimate adjusted HRs for NAFLD associated with biomarkers. RESULTS: In observational analyses, BMI (kg/m2; mean: 23.9 in the subcohort) was associated with 199 metabolites at a 5% false discovery rate. The effects of genetically elevated BMI with specific metabolites were directionally consistent with the observational associations. Overall, 35 metabolites were associated with NAFLD risk, of which 15 were also associated with BMI, including glutamate (HR per 1-SD higher metabolite: 1.95; 95% CI: 1.48, 2.56), cysteine-glutathione disulfide (0.44; 0.31, 0.62), diaclyglycerol (C32:1) (1.71; 1.24, 2.35), behenoyl dihydrosphingomyelin (C40:0) (1.92; 1.42, 2.59), butyrylcarnitine (C4) (1.91; 1.38, 2.35), 2-hydroxybehenate (1.81; 1.34, 2.45), and 4-cholesten-3-one (1.79; 1.27, 2.54). The discriminatory performance of known risk factors was increased when 28 metabolites were also considered simultaneously in the model (weighted C-statistic: 0.84 to 0.90; P < 0.001). CONCLUSIONS: Among relatively lean Chinese adults, a range of metabolomic biomarkers are associated with NAFLD risk and these biomarkers may lie on the pathway between adiposity and NAFLD.
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Adiposidade , Hepatopatia Gordurosa não Alcoólica , Adulto , Biomarcadores , Estudos de Coortes , Humanos , Obesidade/metabolismo , Estudos ProspectivosRESUMO
BACKGROUND: Tobacco smoking is estimated to account for more than 1 million annual deaths in China, and the epidemic continues to increase in men. Large nationwide prospective studies linked to different health records can help to periodically assess disease burden attributed to smoking. We aimed to examine associations of smoking with incidence of and mortality from an extensive range of diseases in China. METHODS: We analysed data from the prospective China Kadoorie Biobank, which recruited 512â726 adults aged 30-79 years, of whom 210â201 were men and 302â525 were women. Participants who had no major disabilities were identified through local residential records in 100-150 administrative units, which were randomly selected by use of multistage cluster sampling, from each of the ten diverse study areas of China. They were invited and recruited between June 25, 2004, and July 15, 2008. Upon study entry, trained health workers administered a questionnaire assessing detailed smoking behaviours and other key characteristics (eg, sociodemographics, lifestyle, and medical history). Participants were followed up via electronic record linkages to death and disease registries and health insurance databases, from baseline to Jan 1, 2018. During a median 11-year follow-up (IQR 10-12), 285â542 (55·7%) participants were ever hospitalised, 48â869 (9·5%) died, and 5252 (1·0%) were lost to follow-up during the age-at-risk of 35-84 years. Cox regression yielded hazard ratios (HRs) associating smoking with disease incidence and mortality, adjusting for multiple testing. FINDINGS: At baseline, 74·3% of men and 3·2% of women (overall 32·4%) ever smoked regularly. During follow-up, 1â137â603 International Classification of Diseases, 10th revision (ICD-10)-coded incident events occurred, involving 476 distinct conditions and 85 causes of death, each with at least 100 cases. Compared with never-regular smokers, ever-regular smokers had significantly higher risks for nine of 18 ICD-10 chapters examined at age-at-risk of 35-84 years. For individual conditions, smokers had significantly higher risks of 56 diseases (50 for men and 24 for women) and 22 causes of death (17 for men and nine for women). Among men, ever-regular smokers had an HR of 1·09 (95% CI 1·08-1·11) for any disease incidence when compared with never-regular smokers, and significantly more episodes and longer duration of hospitalisation, particularly those due to cancer and respiratory diseases. For overall mortality, the HRs were greater in men from urban areas than in men from rural areas (1·50 [1·42-1·58] vs 1·25 [1·20-1·30]). Among men from urban areas who began smoking at younger than 18 years, the HRs were 2·06 (1·89-2·24) for overall mortality and 1·32 (1·27-1·37) for any disease incidence. In this population, 19·6% of male (24·3% of men residing in urban settings and 16·2% of men residing in rural settings) and 2·8% of female deaths were attributed to ever-regular smoking. INTERPRETATION: Among Chinese adults, smoking was associated with higher risks of morbidity and mortality from a wide range of diseases. Among men, the future smoking-attributed disease burden will increase further, highlighting a pressing need for reducing consumption through widespread cessation and uptake prevention. FUNDING: British Heart Foundation, Cancer Research UK, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, UK Medical Research Council, National Natural Science Foundation of China, Wellcome Trust.
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Fumar , Fumar Tabaco , Adulto , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Prospectivos , China/epidemiologia , Efeitos Psicossociais da DoençaRESUMO
OBJECTIVE: To identify factors associated with hypertension control among treated middle-aged UK adults. METHODS: A cross-sectional population-based study including 99 468 previously diagnosed, treated hypertensives enrolled in the UK Biobank. Hypertension control was defined as systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg. RESULTS: Median age was 62.3 years (IQR 57.3 to 66.0), 45.9% female, 92.0% white, 40.1% obese, 9.3% current smokers and 19.4% had prior cardiovascular disease. 38.1% (95% CI 37.8% to 38.4%) were controlled. In multivariable logistic regression, associations with lack of hypertension control included: older age (OR 0.61, 95% CI 0.58 to 0.64 for 60-69 years compared with age 40-50 years), higher alcohol use (OR 0.61, 95% CI 0.58 to 0.64, for consuming >30 units per week compared with none), black ethnicity (OR 0.73, 95% CI 0.65 to 0.82 compared with white), obesity (OR 0.73, 95% CI 0.71 to 0.76 compared with normal body mass index). The strongest positive association with control was having ≥3 comorbidities (OR 2.09, 95% CI 1.95 to 2.23). Comorbidities associated with control included cardiovascular disease (OR 2.11, 95% CI 2.04 to 2.19), migraines (OR 1.68, 95% CI 1.56 to 1.81), diabetes (OR 1.32, 95% CI 1.27 to 1.36) and depression (OR 1.27, 95% CI 1.20 to 1.34). CONCLUSIONS: In one of the largest population-based analyses of middle-aged adults with measured blood pressure, the majority of treated hypertensives were uncontrolled. Risk factors for hypertension were associated with a lower probability of control. Having a comorbidity was associated with higher probability of control, possibly due to more frequent interaction with the healthcare system and/or appropriate management of those at greater cardiovascular risk.
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Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Hipertensão/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Seguimentos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: There is limited nationwide evidence about the standard management characteristics of stroke types and prognosis in China. This study aimed to assess clinical characteristics, in-hospital and after-discharge management characteristics and prognosis for stroke types in China. METHODS: A nationwide registry recruited 14 244 imaging-confirmed first-ever incident strokes from 132 hospitals across 31 provinces of China during 2007-2008, recording presenting characteristics, diagnostic procedures and in-hospital treatment. After hospital discharge, patients were followed up for 6 months. Conventional statistical methods were used to examine the patterns of management and prognosis. RESULTS: Overall, 68.7%, 26.9% and 4.4% were ischaemic stroke (IS), intracerebral haemorrhage (ICH), and subarachnoid haemorrhage (SAH), respectively. Only 20% were managed in a dedicated stroke unit. Among IS, 1.3% received thrombolysis within 3 hours after symptom onset, whereas the proportions of receiving in-hospital antiplatelet therapy, neuroprotective agents and traditional Chinese medicines (TCM) were 88.4%, 69.7% and 70.6%, respectively. For ICH, 63.3% and 36.3% received neuroprotective agents and TCM in hospital, respectively. At discharge, 70.7% and 38.0% of the patients with IS were given antiplatelet and statin therapies, respectively, decreasing to 64.8% and 23.9%, respectively, at 6 months. In-hospital mortality was 3.2%, 9.3% and 10.1% for IS, ICH and SAH, respectively, with a further 8.6%, 18.2% and 22.0%, respectively, died by 6 month. Meanwhile, in-hospital recurrence rate was 2.6%, 1.9% and 7.2% for IS, ICH and SAH, respectively, with a further 8.0%, 5.1% and 7.5%, respectively, recurred by 6 month. CONCLUSIONS: In China, the mortality rate of stroke is lower than that reported from west populations, though most strokes are not managed in specialised stroke unit. There is widespread use of some unproven therapies but limited proven treatments, especially after discharge, leading to unnecessary recurrent risks.
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Isquemia Encefálica , Acidente Vascular Cerebral , China/epidemiologia , Humanos , Prognóstico , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapiaRESUMO
OBJECTIVES: To compare hospital treatments for major stroke types in Chinese adults by stroke pathological types, sex, age, calendar year, hospital tier, region and other factors. DESIGN: Cross-sectional analysis of medical records retrieved from 20 229 stroke cases in the China Kadoorie Biobank. SETTING: Ten diverse areas (five urban, five rural) in China. PARTICIPANTS: First-incident stroke cases who were recruited during an 11-year follow-up of 0.5M participants in the China Kadoorie Biobank. METHODS: Electronic copies of medical records of stroke cases were retrieved for clinical adjudication by local neurologists. Stroke cases were classified as ischaemic stroke (IS) (including lacunar infarction (LACI) and non-LACI (non-LACI)), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) and unspecified stroke types. RESULTS: Among 20 299 first-ever stroke cases, 17 306 (85%) had IS, 7123 had non-LACI, 6690 had LACI, 3493 had silent LACI, 2623 (13%) had ICH and 370 (2%) had SAH. Among IS cases, antiplatelet treatment was used by 64% (65% non-LACI, 66% LACI, 56% silent LACI), lipid-lowering by 50% (52% non-LACI, 53% LACI, 43% silent LACI) and blood pressure-lowering by ~42% of all IS types, with positive trends in the use of these treatments by calendar year and hospital tier. Among ICH cases, 53% used blood pressure-lowering and 10% used lipid-lowering treatments, respectively. In contrast, traditional Chinese medicines (TCMs) were used by 59% of IS (50% non-LACI, 62% LACI, 74% silent LACI), 38% of ICH and 30% of SAH cases, with positive trends by calendar year and by hospital tier. CONCLUSIONS: Among IS cases, use of antiplatelet and lipid-lowering medications increased in recent years, but use of TCM still exceeded use of blood pressure-lowering treatment. In contrast, blood pressure-lowering treatment was widely used for ICH, but only half of all ICH cases used blood pressure-lowering treatment.
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Isquemia Encefálica , Acidente Vascular Cerebral , Adulto , Hemorragia Cerebral/epidemiologia , China/epidemiologia , Estudos Transversais , Hospitais , Humanos , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Widespread use of brain imaging in China has resulted in an increased prevalence of silent lacunar infarct (LACI) in addition to symptomatic LACI, but their clinical relevance is not fully understood. METHODS: We compared the 5-year risks of recurrent stroke and all-cause mortality for silent LACI vs symptomatic LACI in a prospective study of 489,597 Chinese adults with no history of stroke or ischemic heart disease at baseline. Data on recurrent stroke and all-cause mortality were obtained by linkage with local stroke and mortality registries and health insurance records for all hospital admissions. FINDINGS: Among 12,150 cases with an adjudicated diagnosis of first-ever LACI, 4,134 (34%) had silent LACI and 8,016 (66%) had symptomatic LACI. All cases had brain imaging, but only 33% of silent LACI and 40% of symptomatic LACI cases had brain magnetic resonance imaging (MRI). The standardized event rates for silent LACI were 2-fold greater in urban than rural areas, but the ratios of silent LACI vs symptomatic LACI were similar in all areas. Cases with silent LACI vs symptomatic LACI had comparable 5-year risks of recurrent stroke (38% vs 43%) and all-cause mortality (11% vs 14%), respectively. For both silent and symptomatic LACI cases, most cases of recurrent stroke had non-LACI (70% vs 72%). While the relative risks of recurrent stroke did not differ by age, sex and area, the absolute risks of all-cause mortality varied by sex, age and area. INTERPRETATION: The prognosis of cases with silent LACI was comparable with symptomatic LACI, and the results highlight the need for further randomized trials assessing the efficacy and safety of established treatments for ischemic stroke in cases with silent LACI. FUNDING: Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z) and National Key Research and Development Program of China (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) and National Natural Science Foundation of China (91843302); UK Medical Research Council (MC_UU_00017/1,MC_UU_12026/2 MC_U137686851), Cancer Research UK (C16077/A29186; C500/A16896) and British Heart Foundation (CH/1996001/9454). ZH was supported West China Hospital, Sichuan University (ZYGD18009 and 2016YFC1300505) for a visiting scholarship to the University of Oxford, UK, during 2018-19.