Trends in Age of First-Ever Stroke Following Increased Incidence and Life Expectancy in a Low-Income Chinese Population.

BACKGROUND AND PURPOSE: We investigated secular trends in the age of stroke onset and stroke incidence in a low-income population in rural China. METHODS: The study population was recruited from a population-based stroke surveillance study conducted in a township in Tianjin, China, from 1992 to 2014. The trends in mean age and incidence of first-ever stroke were assessed by sex and stroke subtype. Risk factor surveys were conducted in the same population in both 1991 and 2011. RESULTS: A total of 1053 patients experienced first-ever stroke from 1992 to 2014. The mean age of stroke onset in men significantly decreased by 0.28 years annually overall, by 0.56 years for intracerebral hemorrhage, and by 0.22 years for ischemic stroke (P<0.05). However, a similar trend was not observed in women. The age-standardized first-ever stroke incidence in the same population significantly increased across sex and stroke subtypes, increased by 6.3% overall, 5.5% for men, 7.9% for women, 4.6% for intracerebral hemorrhage, and 7.3% for ischemic stroke (P<0.05) during 1992 to 2014. Concurrently, the prevalence of hypertension, diabetes mellitus, obesity, current smoking, and alcohol consumption increased significantly in young and middle-aged adults from 1991 to 2011. CONCLUSIONS: The age of stroke onset tends to be younger among low-income population in China after the dramatic increased incidence of stroke during the gradual extension of life expectancy of population in China. These findings suggested that stroke burden will continue to increase in the long time, unless the risk factors in low-income populations are effectively controlled.

Low total cholesterol level is the independent predictor of poor outcomes in patients with acute ischemic stroke: a hospital-based prospective study.

BACKGROUND: Total cholesterol is a well-documented risk factor for coronary disease. Previous studies have shown that high total cholesterol level is associated with better stroke outcomes, but the association of low total cholesterol levels and ischemic stroke outcomes is rare. Therefore, we aimed to assess the association of low total cholesterol levels and stroke outcomes among acute ischemic stroke patients in China. METHODS: This study recruited 6407 atherothrombotic infarction patients from Tianjin, China, between May 2005 and September 2014. All patients were categorized into five groups according to TC level quintiles at admission. Differences in subtypes, severity, risk factors, and outcomes at 3, 12, and 36 months after stroke were compared between these groups. RESULTS: In total, 1256 (19.6%) patients had low cholesterol levels, with a higher prevalence in men than in women (23.7% vs. 11.2%, P < 0.001). Compared with higher cholesterol levels, the lowest cholesterol level quintile (TC, <4.07 mmol/L) was associated with older age (64.7 years, P = 0.033), anterior circulation infarct (22.8%), atrial fibrillation (4.9%), current smoking (41.1%), and alcohol consumption (21.1%) and lower frequencies of hypertension (72.9%), diabetes (30.7%), and obesity (9.9%). Dependency and recurrence rates were significantly higher at 36 months in patients in the lowest TC level quintile than in those with higher cholesterol levels (dependency rates, 51.2% vs 45.2%; P = 0.007 and recurrence rates, 46.3% vs 37.3%, P = 0.001). Moreover, these differences remained after adjustment for age, sex, stroke severity, and Oxfordshire Community Stroke Project classification (odds ratios [ORs] for dependency rate, 1.41; 95% confidence interval [CI], 1.11, 1.79; P = 0.005 and recurrence rate, 1.50; 95% CI, 1.19, 1.89; P = 0.001). However, mortality rates after stroke were not significantly different between the groups. CONCLUSIONS: These findings suggest that statin treatment for patients with atherothrombotic infarction and low cholesterol levels increase long-term dependency and recurrence rates, but do not increase mortality rates. It is crucial to highlight the different impact of statin treatment on patients with atherothrombotic infarction and lower cholesterol levels for secondary stroke prevention in China.

Low Density Lipoprotein Cholesterol and the Outcome of Acute Ischemic Stroke: Results of a Large Hospital-Based Study.

Studies show inconsistent associations between low-density lipoprotein cholesterol (LDL-C) and stroke outcome. We assessed these associations among patients with first-ever acute ischemic stroke (AIS) in China. Patients with first-ever AIS were categorized into 3 groups: normal LDL, marginally elevated LDL and high LDL - according to the LDL-C values on admission. The outcome measures that were investigated in each group included mortality, dependence and recurrence of vascular events. Patients with high LDL-C had higher mortality rates than did those with normal LDL-C at both 12 and 36 months, but this difference disappeared after adjustment for covariates. There was no difference between groups in mortality at 3 months and dependency or recurrence at 3, 12 or 36 months. LDL-C level was associated with long-term mortality after stroke, but was not an independent prognostic factor.

Moyamoya syndrome as an unusual presenting manifestation of systemic lupus erythematosus in a young woman.

OBJECTIVE: To describe a rare case of moyamoya syndrome associated with systemic lupus erythematosus (SLE). PRESENTATION AND INTERVENTION: A 22-year-old woman presented with left-sided hemiparesis in addition to fever, fatigue and malar rash. Brain magnetic resonance imaging revealed acute infarction in the right middle cerebral artery territory. Cerebral angiography showed features of moyamoya syndrome. Brain biopsy showed evidence of vasculitis. She responded well to steroid therapy. CONCLUSION: This case represented a rare co-occurrence of SLE-related vasculitis and moyamoya syndrome. Early vascular imaging is critical in patients with SLE and suspected ischemic stroke.

Antioxidative polyphenols attenuate pyocyanin-induced ROS production in neuronal HT22 cell lines.

Pyocyanin, a secreted virulence factor, plays an essential role during Pseudomonas aeruginosa infection. Infection of the central nervous system by this bacterium results in high mortality, but the studies on its mechanism are still rather limited. In this study, we first evaluate the neuronal damage caused by pyocyanin exposure in neuronal HT22 cells. Pyocyanin leads to mitochondrial syndrome and antioxidant defense disruption, therefore increasing intercellular reactive oxygen species (ROS) production. Several typical superior antioxidant polyphenols effectively protect against pyocyanin-induced neuronal cell damage. These findings suggest the neuronal protective activity more or less relies on the structure, rather than the residues. Pre-incubation of catechin activates the essential pathway, indicating inverse correlation of ERK and AMPK phosphorylation participates in this process. These data outline a novel strategy to eliminate intracellular generated ROS. The investigated candidates could be potentially used as therapeutic agents against various ROS-related neurological diseases.

Whole genome sequencing of 10K patients with acute ischaemic stroke or transient ischaemic attack: design, methods and baseline patient characteristics.

BACKGROUND AND PURPOSE: Stroke is the second leading cause of death worldwide and the leading cause of mortality and long-term disability in China, but its underlying risk genes and pathways are far from being comprehensively understood. We here describe the design and methods of whole genome sequencing (WGS) for 10 914 patients with acute ischaemic stroke or transient ischaemic attack from the Third China National Stroke Registry (CNSR-III). METHODS: Baseline clinical characteristics of the included patients in this study were reported. DNA was extracted from white blood cells of participants. Libraries are constructed using qualified DNA, and WGS is conducted on BGISEQ-500 platform. The average depth is intended to be greater than 30× for each subject. Afterwards, Sentieon software is applied to process the sequencing data under the Genome Analysis Toolkit best practice guidance to call genotypes of single nucleotide variants (SNVs) and insertion-deletions. For each included subject, 21 fingerprint SNVs are genotyped by MassARRAY assays to verify that DNA sample and sequencing data originate from the same individual. The copy number variations and structural variations are also called for each patient. All of the genetic variants are annotated and predicted by bioinformatics software or by reviewing public databases. RESULTS: The average age of the included 10 914 patients was 62.2±11.3 years, and 31.4% patients were women. Most of the baseline clinical characteristics of the 10 914 and the excluded patients were balanced. CONCLUSIONS: The WGS data together with abundant clinical and imaging data of CNSR-III could provide opportunity to elucidate the molecular mechanisms and discover novel therapeutic targets for stroke.

Attenuated glutamate induced ROS production by antioxidative compounds in neural cell lines.

Glutamate is an excitatory neurotransmitter involved in neural function. Excess accumulation of intercellular glutamate leads to increasing concentration of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in neuronal cells. In this study, we investigated the antioxidant activity of several typical superior compounds among four neuronal cells, and determined the scavenging activity of free radicals. The in vivo assay was also carried out to compare the protective effect of glutamate-induced cell damage. Hierarchical clustering analysis was used to identify the common properties. Glutamate induced neurotoxicity and ROS production, suggesting glutamate cytotoxicity was related to oxidative stress and widely exists in different cell lines. Those screening compounds exhibited strong antioxidant ability, but low cytotoxicity to neuronal cells, acting as agents against neurodegenerative diseases. Finally, a hierarchical clustering analysis assay indicated that hyperoside and rutin hydrate are the most effective compounds for attenuating intercellular ROS levels. The results suggested the activity more or less relies on structure, rather than residues. These data generate new supporting ideas to remove intracellular ROS and the identified compounds serve as potential therapeutic agents in multiple neurological diseases.

Trends in the incidence of recurrent stroke at 5 years after the first-ever stroke in rural China: a population-based stroke surveillance from 1992 to 2017.

Recent data on the incidence and trends for recurrent strokes in China are scarce. We assessed the temporal trends in recurrent stroke incidence using in rural China. The age-standardized incidences of recurrent stroke, within 5 years of the incident stroke event, were estimated for 3 time periods: 1992-1998, 1999-2005, and 2006-2012. Among the 768 documented incident stroke cases, 26.3% of the patients experienced recurrent stroke within 5 years. The overall age-adjusted recurrent stroke incidence was 43.93 per 100,000 person-years (1992-2012). During the 2006-2012 period, the recurrent stroke incidence per 100,000 person-years was 107.79 in men, and 557.76 in individuals ≥65 years old. There were significant upward tendencies observed in this population across sex, age, or type of stroke (except for among individuals ≥65 years old with incident intracerebral hemorrhages). Compared with the recurrent stroke incidence observed in the 1992-1998 period, that observed during the 2006-2012 period was more than 3-fold higher; the greatest increase (6.8-fold) was observed in women. These findings suggest an urgent need to improve risk factor management and implement appropriate medical resources to contain this upward trend in recurrent stroke incidence and reduce the overall stroke burden in China.

Hesperidin attenuates learning and memory deficits in APP/PS1 mice through activation of Akt/Nrf2 signaling and inhibition of RAGE/NF-κB signaling.

Numerous studies have demonstrated that oxidative stress and inflammation play a pivotal role in the pathophysiology of Alzheimer disease (AD). Hesperidin (HP) has various pharmacological effects including anti-oxidative, anti-inflammatory and neuroprotective properties. In this study, APP/PS1 mice were used to evaluate the neuroprotective effects of HP. We reported that intragastric administration of HP (40 mg/kg) for 90 days significantly attenuated cognitive impairment in APP/PS1 mice. HP treatment suppressed oxidative stress by reducing the levels of ROS, LPO, protein carbonyl and 8-OHdG and increasing the activity of HO-1, SOD, catalase, and GSH-Px. HP treatment also inhibited inflammation by decreasing the levels of TNF-α, C-reactive protein and MCP-1 and reducing the activity of NF-κB. Moreover, HP could reverse the decreased phosphorylation of Akt, the decreased phosphorylation of GSK-3ß, the lessened Nrf2 and the reduced expression of HO-1. HP could also inhibit the increased the RAGE expression, the enhanced phosphorylation of IκBα, and the augmented nuclear translocation of NF-κB/p65 in cortex of APP/PS1 mice. Taken together, HP suppresses oxidative stress and inflammation via activation of Akt/Nrf2 signaling and inhibition of RAGE/NF-κB signaling and further confers neuroprotection.

Sex differences in outcomes and associated factors among stroke patients with small artery occlusion in China.

BACKGROUND: Sex differences in outcomes after small artery occlusion (SAO) stroke have not been well described, particularly in a Chinese population. We aimed to assess sex differences in outcomes and related risk factors among patients with SAO. METHODS: All consecutive patients with SAO were recruited between May 2005 and September 2014. Clinical features and risk factors were recorded. The mortality, recurrence, and dependency rates at 3 months after stroke were assessed. RESULTS: A total of 2524 patients with SAO were included in this study. There was a higher frequency of mild stroke, current smoking, and alcohol consumption in men than in women. Women were more likely than men to be older, to have diabetes and obesity, and to have higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. There were worse outcomes in men than in women at 3 months after stroke (P < 0.05). There were more independent risk factors of poor outcome in men than in women. Older age was a common predictive factor of outcome both in men and in women. In men, low triglyceride levels and high fasting plasma glucose levels were independent risk factors for mortality; in addition, a high low-density lipoprotein cholesterol level was associated with recurrence. Moreover, in men, moderate and severe stroke, and high total cholesterol and fasting plasma glucose levels were risk factors for dependency. A negative association was found between low-density lipoprotein cholesterol level and risk of mortality and between total cholesterol level and risk of recurrence in women. CONCLUSIONS: These findings suggest that it is crucial to control conventional risk factors and fasting plasma glucose and lipid levels among patients with SAO, especially male patients, to reduce the burden of stroke in China.

Effect of age on long-term outcomes after stroke with atrial fibrillation: a hospital-based follow-up study in China.

Atrial fibrillation (AF) is an established predictor of poor outcomes after stroke. We aimed to assess the effect of age on outcomes at 1 year and 3 years in stroke patients with AF. We recruited acute ischemic stroke patients with AF between January 2006 and September 2014 in Tianjin, China. Clinical features and outcomes at 1 year and 3 years after stroke were compared between younger group and elderly group. Overall, 951 consecutive stroke patients with AF were included in this study. There was a higher mortality and dependency rate in the elderly group than in the young group at both 1 and 3 years after stroke. Recurrence rates were significantly higher in the elderly group than in the young group at 3 years after stroke. The higher risks of mortality and dependency in elderly patients remained unchanged, but disappeared in recurrence rates after adjusting for stroke subtype, severity, risk factors, and lifestyle. These findings suggest that it is crucial to highlight the treatment of elderly stroke patients with AF in order to reduce poor outcomes and to reduce the burden of AF in China.

Sex Differences in the Clinical Features, Risk Factors, and Outcomes of Intracerebral Hemorrhage: a Large Hospital-based Stroke Registry in China.

Intracerebral hemorrhage (ICH) is common in China. However, the sex differences in clinical features, risk factors, and outcomes of ICH remain controversial. Between 2005 and 2014, we recruited patients with primary ICH in Tianjin, China, and evaluated sex differences in clinical features, risk factors, and outcomes at 3, 12, and 36 months after ICH. The 1,325 patients included 897 men (67.7%) and 428 women (32.3%). The mean age at ICH onset was younger among men (59.14 years) than among women (63.12 years, P < 0.001). Men were more likely to have a hematoma in the basal ganglia, while women were more likely to have one in the thalamus. Women had higher frequencies of urinary tract infections, diabetes mellitus, cardiovascular diseases, and obesity. Men had a greater risk of death at 3 months after ICH. However, no sex differences were observed for mortality at 12 and 36 months after ICH or for recurrence and dependency at 3, 12, and 36 months after ICH. These findings suggested that it crucial to strengthen management of AF and complications in patients with ICH, especially management of blood pressure in men for reducing the mortality rates and the burden of ICH in China.

Sex Differences in Outcomes among Stroke Survivors with Non-Valvular Atrial Fibrillation in China.

Atrial fibrillation (AF) significantly increases the risk of stroke and disease burden and is an established predictor of poor outcomes after stroke. However, data regarding sex differences in long-term outcomes following stroke in patients with AF are scarce. We thus aimed to assess these differences. We recruited 951 consecutive patients with acute ischemic stroke and non-valvular atrial fibrillation (NVAF) treated at three hospitals in Tianjin, China, from January 2006 to September 2014. Information regarding stroke subtype, severity, risk factors, and outcomes (mortality, dependency, and recurrence) at 3, 12, and 36 months after stroke was recorded. The prevalence of NVAF was 8.4% overall, with a higher frequency in women than in men (11.3 vs. 6.9%, P < 0.001). Among patients with NVAF, women were older than men. Women were more likely than men to have severe stroke (38.8 vs. 29.5%, P < 0.001), high levels of total cholesterol and high- and low-density lipoprotein cholesterol (all P < 0.001), hypertension (69.1 vs. 61.2%, P = 0.012), dyslipidemia (29.8 vs. 20.7%, P = 0.001), and obesity (18.5 vs. 11.6%, P = 0.003); they were less likely than men to be current smokers (12.2 vs. 33.6%, P < 0.001) and to consume alcohol (0.9 vs. 13.9%, P < 0.001). There were greater risks of dependency and recurrence at 36 months after stroke in women than in men [odds ratios (95% confidence intervals), 1.64 (1.02-2.64) for dependency, P = 0.043; and 2.03 (1.28-3.20) for recurrence, P = 0.002] after adjustment for stroke subtype, severity, and risk factors. These findings suggest that it is crucial to emphasize the need for individualized stroke prevention education and promotion of healthy lifestyles in order to improve NVAF-related stroke outcomes and reduce disease burden in women.

Sex differences in outcomes after stroke among patients with low total cholesterol levels: a large hospital-based prospective study.

BACKGROUND: Previous studies have shown that total cholesterol (TC) levels are associated with stroke outcomes, but sex differences in the association between TC levels, especially a low TC level, and ischemic stroke outcomes are unknown. We aimed to assess the sex differences in stroke outcomes among patients with atherothrombotic infarctions and low TC levels in China. METHODS: This study recruited patients with atherothrombotic infarctions from Tianjin, China, between May 2005 and September 2014. Patients with low TC levels (defined as TC <4.22 mmol/L) were analyzed in this study. Sex differences in stroke subtypes, severity, risk factors, and outcomes at 3 and 12 months after stroke were compared. RESULTS: Overall, 1587 patients with low TC levels were recruited to this study from among 6407 patients with atherothrombotic infarctions listed in a stroke registry. Women were more likely than men to have posterior circulation infarcts, severe stroke, hypertension, and obesity but less likely to be current smokers or to consume alcohol. There were no sex differences in stroke outcomes. Older age and severe stroke were common risk factors for poor outcomes after stroke in this study. The presence of diabetes mellitus was an independent predictor of low mortality at 12 months after stroke, possibly because a drug commonly used to treat diabetes, metformin, enhances angiogenesis. Obesity was the determinant of the recurrence and dependency rates at 12 months after stroke. CONCLUSIONS: These findings suggest that patients (both men and women) with atherothrombotic infarction who have low TC levels would not benefit from receiving statin treatment. Therefore, it is crucial to explore the impact of statin treatment on outcomes in Asian patients, especially Chinese patients with atherothrombotic and low TC levels, in order to improve outcomes after stroke and reduce the disease burden.

Mortality, Recurrence, and Dependency Rates Are Higher after Acute Ischemic Stroke in Elderly Patients with Diabetes Compared to Younger Patients.

Stroke has a greater effect on the elderly than on younger patients. However, the long-term outcomes associated with stroke among elderly patients with diabetes are unknown. We aimed to assess the differences in long-term outcomes between young and elderly stroke patients with diabetes. A total of 3,615 acute ischemic stroke patients with diabetes were recruited for this study between 2006 and 2014. Outcomes at 12 and 36 months after stroke (including mortality, recurrence, and dependency) were compared between younger (age <75 years) and elderly (age ≥75 years) patients. The elderly group included 692 patients (19.1%) overall. Elderly patients were more likely than younger patients to have a Trial of Org 10172 in Acute Stroke Treatment classification of stroke due to cardioembolism, moderate and severe stroke, and atrial fibrillation, but less likely to have hypertension and dyslipidemia, current smokers, and alcohol consumers. Mortality, dependency, and recurrence rates at 12 months after stroke were 19.0, 48.5, and 20.9% in the elderly group and 7.4, 30.9, and 15.4% in the younger group, respectively (all P < 0.05). Corresponding rates at 36 months after stroke were 35.4, 78.7, and 53.8% in the elderly group and 13.7, 61.7, and 43.0% in the younger group, respectively (all P < 0.001). The mortality, dependency, and recurrence rates at 12 and 36 months after stroke were significantly higher in the elderly group than in the younger group after adjusting for stroke subtypes, stroke severity, and risk factors. Odds ratios (95% confidence interval) at 12 and 36 months after stroke were 2.18 (1.64-2.89) and 3.10 (2.35-4.08), respectively, for mortality, all P < 0.001; 1.81 (1.49-2.20) and 2.04 (1.57-2.34), respectively, for dependency, all P < 0.001; and 1.37 (1.06-1.76) and 1.40 (1.07-1.85), respectively, for recurrence, P = 0.016. The findings from this study suggest that management and secondary prevention should be emphasized in elderly patients with diabetes in China to reduce mortality, recurrence, and dependency after stroke.

Sex Differences in Stroke Subtypes, Severity, Risk Factors, and Outcomes among Elderly Patients with Acute Ischemic Stroke.

BACKGROUND: Although the age-specific incidence and mortality of stroke is higher among men, stroke has a greater clinical effect on women. However, the sex differences in stroke among elderly patients are unknown. Therefore, we aimed to assess the sex differences in stroke among elderly stroke patients. METHODS: Between 2005 and 2013, we recruited 1484 consecutive acute ischemic stroke (AIS) patients (≥75 years old) from a specialized neurology hospital in Tianjin, China. Information regarding their stroke subtypes, severity, risk factors, and outcomes at 3 and 12 months after stroke were recorded. RESULTS: Comparing with men, women had a significantly higher prevalence of severe stroke (17.20 vs. 12.54%), hypertension (76.42 vs. 66.39%), dyslipidemias (30.35 vs. 22.76%), and obesity (18.40 vs. 9.32%), P < 0.05. Comparing with women, men had a significantly higher prevalence of intracranial artery stenosis (23.11 vs. 17.45%), current smoking (29.60 vs. 13.05%), and alcohol consumption (12.15 vs. 0.47%), P < 0.05. Moreover, dependency was more common among women at 3 and 12 months after stroke, although the sex difference disappeared after adjusting for stroke subtypes, severity, and risk factors. CONCLUSION: Elderly women with AIS had more severe stroke status and worse outcomes at 3 and 12 months after stroke. Thus, elderly female post-AIS patients are a crucial population that should be assisted with controlling their risk factors for stroke and changing their lifestyle.

Sex differences in long-term outcomes among acute ischemic stroke patients with diabetes in China.

BACKGROUND: Diabetes has been shown to be significantly associated with poor outcome after stroke. However, the sex differences in stroke outcome among patients with diabetes are unknown. Therefore, we aimed to assess the sex differences in long-term prognosis among acute ischemic stroke patients with diabetes. METHODS: The ischemic stroke patients with diabetes were recruited to this study between May 2005 and September 2014 in Tianjin, China. Sex differences in mortality, dependency (modified rank scale > 2), and recurrence at 3, 12, and 36 months after stroke were analyzed. RESULTS: A total of 2360 patients were recruited in this study. The age of stroke onset, National Institute of Health stroke scale (NIHSS), and modified rank scale (mRS) on admission were greater in women than in men (P < 0.05). Women were more likely to have hypertension, obesity, atrial fibrillation, and dyslipidemias. In contrast, men were more likely to have artery stenosis, current smoking, and alcohol consumption (P < 0.001). There was higher mortality in women than in men at 3 months (7.9 % vs 5.2 %), 12 months (12.2 % vs 8.2 %), and 36 months (21.9 % vs 16.1 %) after stroke; but no differences were found in dependency and recurrence. Sex differences were found in associated factors of outcomes by time-point. Trial of Org 10172 in Acute Stroke Treatment (TOAST) of large artery atherothrombosis (LAA), cardioembolism (CE), and smoking were risk factors of outcomes in women at short term and medium term; but atrial fibrillation (AF), obesity, and alcohol were risk factors of outcomes in men at medium term and long term. CONCLUSIONS: These findings suggest that it is crucial to establish the individual scheme of therapy for every patient by different risk factors of stroke, strengthen the rehabilitation of stroke, and carry on the health education early for the secondary prevention of stroke in patients with diabetes mellitus (DM).

Increasing stroke incidence and prevalence of risk factors in a low-income Chinese population.

OBJECTIVE: We investigated secular trends in incidence of first-ever stroke and the prevalence of stroke risk factors within the same population in rural China. METHODS: In 1985, 15,438 residents from a township of Tianjin, China, were recruited to the Tianjin Brain Study, a population-based stroke surveillance study. Stroke events and all deaths were registered annually. Because imaging technology was first available in 1992, we analyzed the incidence of first-ever stroke over 3 study periods-1992-1998, 1999-2005, and 2006-2012-from 1992 to 2012. Risk factor surveys were conducted in 1991 and 2011. RESULTS: The age-standardized incidence of first-ever stroke per 100,000 person-years increased rapidly from 124.5 in 1992-1998 to 190.0 in 1999-2005 and to 318.2 in 2006-2012; incidence increased annually by 6.5% overall and by 12% among men aged 45-64 years (p < 0.05). From 1992 to 2012, the age at first-ever stroke in men was earlier by 3.3 years overall, but a similar trend was not observed in women. Concurrently, the prevalence of high fasting glucose and alcohol consumption increased significantly in both men and women, especially in men aged <45 years; the prevalence of obesity and high fasting glucose increased by 8.8-fold and 11-fold, respectively, from 1992 to 2012. CONCLUSIONS: The incidence of stroke in rural China increased rapidly, particularly among middle-aged adults, along with a concurrent increase in risk factor prevalence. These findings suggest that without controlling these risk factors, stroke incidence will continue to increase over future decades in China.