RESUMO
The increasing attention towards diabetic cardiomyopathy as a distinctive complication of diabetes mellitus has highlighted the need for standardized diagnostic criteria and targeted treatment approaches in clinical practice. Ongoing research is gradually unravelling the pathogenesis of diabetic cardiomyopathy, with a particular emphasis on investigating various post-translational modifications. These modifications dynamically regulate protein function in response to changes in the internal and external environment, and their disturbance of homeostasis holds significant relevance for the development of chronic ailments. This review provides a comprehensive overview of the common post-translational modifications involved in the initiation and progression of diabetic cardiomyopathy, including O-GlcNAcylation, phosphorylation, methylation, acetylation and ubiquitination. Additionally, the review discusses drug development strategies for targeting key post-translational modification targets, such as agonists, inhibitors and PROTAC (proteolysis targeting chimaera) technology that targets E3 ubiquitin ligases.
Assuntos
Diabetes Mellitus , Cardiomiopatias Diabéticas , Humanos , Cardiomiopatias Diabéticas/genética , Processamento de Proteína Pós-Traducional , Ubiquitinação , Fosforilação , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention on cardiovascular disease has not been established. We aimed to test the effectiveness of such an intervention compared with usual care on risk of cardiovascular disease and all-cause death among individuals with hypertension. METHODS: In this open-label, blinded-endpoint, cluster-randomised trial, we recruited individuals aged at least 40 years with an untreated systolic blood pressure of at least 140 mm Hg or a diastolic blood pressure of at least 90 mm Hg (≥130 mm Hg and ≥80 mm Hg for those at high risk for cardiovascular disease or if currently taking antihypertensive medication). We randomly assigned (1:1) 326 villages to a non-physician community health-care provider-led intervention or usual care, stratified by provinces, counties, and townships. In the intervention group, trained non-physician community health-care providers initiated and titrated antihypertensive medications according to a simple stepped-care protocol to achieve a systolic blood pressure goal of less than 130 mm Hg and diastolic blood pressure goal of less than 80 mm Hg with supervision from primary care physicians. They also delivered discounted or free antihypertensive medications and health coaching for patients. The primary effectiveness outcome was a composite outcome of myocardial infarction, stroke, heart failure requiring hospitalisation, and cardiovascular disease death during the 36-month follow-up in the study participants. Safety was assessed every 6 months. This trial is registered with ClinicalTrials.gov, NCT03527719. FINDINGS: Between May 8 and Nov 28, 2018, we enrolled 163 villages per group with 33 995 participants. Over 36 months, the net group difference in systolic blood pressure reduction was -23·1 mm Hg (95% CI -24·4 to -21·9; p<0·0001) and in diastolic blood pressure reduction, it was -9·9 mm Hg (-10·6 to -9·3; p<0·0001). Fewer patients in the intervention group than the usual care group had a primary outcome (1·62% vs 2·40% per year; hazard ratio [HR] 0·67, 95% CI 0·61-0·73; p<0·0001). Secondary outcomes were also reduced in the intervention group: myocardial infarction (HR 0·77, 95% CI 0·60-0·98; p=0·037), stroke (0·66, 0·60-0·73; p<0·0001), heart failure (0·58, 0·42-0·81; p=0·0016), cardiovascular disease death (0·70, 0·58-0·83; p<0·0001), and all-cause death (0·85, 0·76-0·95; p=0·0037). The risk reduction of the primary outcome was consistent across subgroups of age, sex, education, antihypertensive medication use, and baseline cardiovascular disease risk. Hypotension was higher in the intervention than in the usual care group (1·75% vs 0·89%; p<0·0001). INTERPRETATION: The non-physician community health-care provider-led intensive blood pressure intervention is effective in reducing cardiovascular disease and death. FUNDING: The Ministry of Science and Technology of China and the Science and Technology Program of Liaoning Province, China.
Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Hipertensão , Hipotensão , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Doenças Cardiovasculares/complicações , Pressão Sanguínea , Anti-Hipertensivos/uso terapêutico , Saúde Pública , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Hipotensão/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológicoRESUMO
BACKGROUND: The 2018/2023 ESC/ESH Guidelines underlined a gap how baseline cardiovascular disease (CVD) risk predicted blood pressure (BP) lowering benefits. Further, 2017 ACC/AHA Guideline and 2021 WHO Guideline recommended implementation studies about intensive BP control. Now, to bridge these guideline gaps, we conducted a post hoc analysis to validate whether the baseline CVD risk influences the effectiveness of the intensive BP control strategy, which was designed by China Rural Hypertension Control Project (CRHCP). METHODS: This is a post hoc analysis of CRHCP, among which participants were enrolled except those having CVD history, over 80 years old, or missing data. Subjects were stratified into quartiles by baseline estimated CVD risk and then grouped into intervention and usual care group according to original assignment in CRHCP. Participants in the intervention group received an integrated, multi-faceted treatment strategy, executed by trained non-physician community health-care providers, aiming to achieve a BP target of < 130/80 mmHg. Cox proportional-hazards models were used to estimate the hazard ratios of outcomes for intervention in each quartile, while interaction effect between intervention and estimated CVD risk quartiles was additionally assessed. The primary outcome comprised myocardial infarction, stroke, hospitalization for heart failure, or CVD deaths. RESULTS: Significant lower rates of primary outcomes for intervention group compared with usual care for each estimated CVD risk quartile were reported. The hazard ratios (95% confidence interval) in the four quartiles (from Q1 to Q4) were 0.59 (0.40, 0.87), 0.54 (0.40, 0.72), 0.72 (0.57, 0.91) and 0.65 (0.53, 0.80), respectively (all Ps < 0.01). There's no significant difference of hazard ratios by intervention across risk quartiles (P for interaction = 0.370). Only the relative risk of hypotension, not symptomatic hypotension, was elevated in the intervention group among upper three quartiles. CONCLUSIONS: Intensive BP lowering strategy designed by CRHCP group was effective and safe in preventing cardiovascular events independent of baseline CVD risk. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov, NCT03527719.
Assuntos
Doenças Cardiovasculares , Hipertensão , Humanos , Masculino , Feminino , China/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Pressão Sanguínea/fisiologia , População Rural , Anti-Hipertensivos/uso terapêutico , Resultado do Tratamento , Fatores de Risco de Doenças CardíacasRESUMO
Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a key factor in the morbidity and mortality of many CVDs. Cardiomyocyte death can be regulated by specific signaling pathways known as programmed cell death (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, etc. Abnormalities in PCD can lead to the development of a variety of cardiovascular diseases, and there are also molecular-level interconnections between different PCD pathways under the same cardiovascular disease model. Currently, the link between programmed cell death in cardiomyocytes and cardiovascular disease is not fully understood. This review describes the molecular mechanisms of programmed death and the impact of cardiomyocyte death on cardiovascular disease development. Emphasis is placed on a summary of drugs and potential therapeutic approaches that can be used to treat cardiovascular disease by targeting and blocking programmed cell death in cardiomyocytes.
Assuntos
Doenças Cardiovasculares , Miócitos Cardíacos , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Miócitos Cardíacos/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Animais , Apoptose/efeitos dos fármacos , Transdução de Sinais , Fármacos Cardiovasculares/uso terapêutico , Fármacos Cardiovasculares/farmacologiaRESUMO
BACKGROUND: The prevalence of uncontrolled hypertension is high and increasing in low-income and middle-income countries. We tested the effectiveness of a multifaceted intervention for blood pressure control in rural China led by village doctors (community health workers on the front line of primary health care). METHODS: In this open, cluster randomised trial (China Rural Hypertension Control Project), 326 villages that had a regular village doctor and participated in the China New Rural Cooperative Medical Scheme were randomly assigned (1:1) to either village doctor-led multifaceted intervention or enhanced usual care (control), with stratification by provinces, counties, and townships. We recruited individuals aged 40 years or older with an untreated blood pressure of 140/90 mm Hg or higher (≥130/80 mm Hg among those with a history of cardiovascular disease, diabetes, or chronic kidney disease) or a treated blood pressure of 130/80 mm Hg or higher. In the intervention group, trained village doctors initiated and titrated antihypertensive medications according to a standard protocol with supervision from primary care physicians. Village doctors also conducted health coaching on home blood pressure monitoring, lifestyle changes, and medication adherence. The primary outcome (reported here) was the proportion of patients with a blood pressure of less than 130/80 mm Hg at 18 months. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03527719, and is ongoing. FINDINGS: Between May 8 and November 28, 2018, we enrolled 33 995 individuals from 163 intervention and 163 control villages. At 18 months, 8865 (57·0%) of 15 414 patients in the intervention group and 2895 (19·9%) of 14 500 patients in the control group had a blood pressure of less than 130/80 mm Hg, with a group difference of 37·0% (95% CI 34·9 to 39·1%; p<0·0001). Mean systolic blood pressure decreased by -26·3 mm Hg (95% CI -27·1 to -25·4) from baseline to 18 months in the intervention group and by -11·8 mm Hg (-12·6 to -11·0) in the control group, with a group difference of -14·5 mm Hg (95% CI -15·7 to -13·3 mm Hg; p<0·0001). Mean diastolic blood pressure decreased by -14·6 mm Hg (-15·1 to -14·2) from baseline to 18 months in the intervention group and by -7·5 mm Hg (-7·9 to -7·2) in the control group, with a group difference of -7·1 mm Hg (-7·7 to -6·5 mm Hg; p<0·0001). No treatment-related serious adverse events were reported in either group. INTERPRETATION: Compared with enhanced usual care, village doctor-led intervention resulted in statistically significant improvements in blood pressure control among rural residents in China. This feasible, effective, and sustainable implementation strategy could be scaled up in rural China and other low-income and middle-income countries for hypertension control. FUNDING: Ministry of Science and Technology of China.
Assuntos
Hipertensão , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , China/epidemiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/prevenção & controleRESUMO
Cardiovascular disease (CVD) is a major threat to human health, accounting for 46% of non-communicable disease deaths. Glycolysis is a conserved and rigorous biological process that breaks down glucose into pyruvate, and its primary function is to provide the body with the energy and intermediate products needed for life activities. The non-glycolytic actions of enzymes associated with the glycolytic pathway have long been found to be associated with the development of CVD, typically exemplified by metabolic remodeling in heart failure, which is a condition in which the heart exhibits a rapid adaptive response to hypoxic and hypoxic conditions, occurring early in the course of heart failure. It is mainly characterized by a decrease in oxidative phosphorylation and a rise in the glycolytic pathway, and the rise in glycolysis is considered a hallmark of metabolic remodeling. In addition to this, the glycolytic metabolic pathway is the main source of energy for cardiomyocytes during ischemia-reperfusion. Not only that, the auxiliary pathways of glycolysis, such as the polyol pathway, hexosamine pathway, and pentose phosphate pathway, are also closely related to CVD. Therefore, targeting glycolysis is very attractive for therapeutic intervention in CVD. However, the relationship between glycolytic pathway and CVD is very complex, and some preclinical studies have confirmed that targeting glycolysis does have a certain degree of efficacy, but its specific role in the development of CVD has yet to be explored. This article aims to summarize the current knowledge regarding the glycolytic pathway and its key enzymes (including hexokinase (HK), phosphoglucose isomerase (PGI), phosphofructokinase-1 (PFK1), aldolase (Aldolase), phosphoglycerate metatase (PGAM), enolase (ENO) pyruvate kinase (PKM) lactate dehydrogenase (LDH)) for their role in cardiovascular diseases (e.g., heart failure, myocardial infarction, atherosclerosis) and possible emerging therapeutic targets.
Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Humanos , Fosforilação Oxidativa , Aldeído Liases , Redes e Vias MetabólicasRESUMO
BACKGROUND: Cardiovascular disease (CVD) brings high mortality and economic burden to patients, especially in rural areas. Simple, low-cost abdominal adiposity measures may help identify individuals with increased CVD risk. It is unclear that which obesity indices is the best to predict CVD in hypertensive people. METHODS: Northeast China Rural Cardiovascular Health Study (NCRCHS) is a prospective cohort study in a general population in Northeast China. The study examined the cardiovascular health from 2013 to 2015, and follow-up captured the CVD incidence in 2018. Baseline waist-to-height ratio (WHtR), waist circumference (WC), waist-to-hip (WHR)and body mass index (BMI) were calculated and analyzed in relation to the CVD incidence. RESULTS: A total of 4244 hypertensive adults without pre-existing CVD at baseline were included in this analysis (age 35-92 years; 2108 men). Over a median follow-up of 4.66 years, a total of 290 CVD cases (6.83%) were documented during the follow-up. Baseline WHtR showed a significant positive association with CVD incidence, even after adjusting for age, sex, diabetes, drinking, smoking, SBP, DBP, Triglyceride, HDL-C, LDL-C, and TC (Hazard Ratios per SD of WHtR ranging from 1.03 to 1.31, p = 0.017). Reclassification and discrimination analyses indicated WHtR addition could improve the conventional model for predicting adverse outcomes within 4 years. Moreover, WHtR predicted the CVD incidence better than other obesity indices (BMI, WC, WHR). CONCLUSION: These findings support a positive association between WHtR and CVD incidence in CVD-free hypertensive adults. WHtR can be used to predict CVD incidence in hypertensive adults.
Assuntos
Doenças Cardiovasculares , Hipertensão , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/epidemiologia , Estudos Prospectivos , Fatores de Risco , Circunferência da Cintura , Razão Cintura-Estatura , Relação Cintura-QuadrilRESUMO
BACKGROUND: To investigate the combined effect of hypertension and hyperuricemia to the risk of ischemic stroke in a rural Chinese population. METHODS: The cross-sectional study was conducted from 2012 to 2013 in a rural area of China. After exclusion for missing data, we finally included 11,731 participants into analysis. RESULTS: After adjusting for age, current smoking, current drinking, BMI, TG, HDL-C and eGFR, hypertension was significantly associated with ischemic stroke in men (OR: 2.783, 95% CI: 1.793, 4.320) and in women (OR: 4.800, 95% CI: 2.945, 7.822). However, hyperuricemia was significantly associated with ischemic stroke only in women (OR: 1.888, 95% CI: 1.244, 2.864). After full adjustment, participants with both hypertension and hyperuricemia had 8.9 times higher risk than those without them. Finally, the interaction between hypertension and hyperuricemia was statistically significant only in women rather than in men after full adjustment. CONCLUSIONS: This study demonstrated the positive correlations between hypertension, hyperuricemia and ischemic stroke. Our study also demonstrated the joint effect between hypertension and hyperuricemia towards ischemic stroke only in women, not in men.
Assuntos
Isquemia Encefálica , Hipertensão , Hiperuricemia , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hipertensão/epidemiologia , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Masculino , Fatores de Risco , População Rural , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: The new ACC/AHA hypertension guideline lower the definition of hypertension from 140/90 mmHg to 130/80 mmHg and eliminate the category of prehypertension thus increasing the prevalence of hypertension. A purpose of this study is to explore the applicability of the new guidelines in rural China. METHODS: In total, 3229 participants aged ≥35 years and free of stroke at baseline were followed for up to 4.8 years during 2012 to 2017 in a rural community-based prospective cohort study of Xifeng County. The hazard ratio (HR) and 95% Confidence interval (CI) of different blood pressure (BP) levels for risk of incident stroke were analyzed by multivariable Cox proportional hazard models. RESULTS: During the follow-up, 81 new strokes occurred among the 3229 participants. Compared with normal BP (Systolic BP (SBP)<120 mmHg and Diastolic BP (DBP)<80 mmHg), stage 2 hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg) had approximately 2.1 greater risks for stroke (HR: 2.10, 95% CI: 1.13 to 3.91, P = 0.020). However, there was no significant association between elevated (SBP:120-129 mmHg and DBP<80 mmHg), stage1 hypertension (SBP:130-139 mmHg or DBP:80-89 mmHg) and stroke incidence (HR: 0.93, 95% CI: 0.33 to 2.61, P = 0.888; HR: 0.96, 95% CI: 0.46 to 2.02, P = 0.920, respectively). An increase of the SBP by 1-SD increases the risk for stroke by 56% (HR: 1.56, 95%CI: 1.29 to 1.88, P < 0.001). An increase of the SBP by 20 mmHg increases the risk for stroke by 51% (HR: 1.51, 95%CI: 1.27 to 1.80, P < 0.001). CONCLUSIONS: Compared with normal BP, the stage 2 hypertension based on 2017 ACC/AHA guideline significantly increases the risk of stroke incidence, but this association was not observed between elevated, stage1 hypertension and stroke incidence in Chinese rural adults.
Assuntos
Pressão Sanguínea , Hipertensão/epidemiologia , Saúde da População Rural , Acidente Vascular Cerebral/epidemiologia , Adulto , China/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND AND AIMS: Obesity and insulin levels can influence each other by metabolism. However, their temporal sequences and influence on hypertension are generally unknown, especially in Chinese adults. Recently, some scholars have proposed that triglycerides-glucose index (TyG) is an important indicator of insulin resistance. The study aims to describe the relationship between body mass index (BMI) and TyG index and its impact on hypertension. METHODS AND RESULTS: A total of 4081 adults (56.33% women) without antihypertensive, hypoglycemic or lipid-lowering medications were selected for the present study. Measurements of BMI and TyG index were obtained twice from 2012 to 2017. Cross-lagged panel analysis was used to describe the temporal sequences between BMI and TyG index, and the effect of their temporal relationship patterns on hypertension was explored through mediation analysis. After adjusting for confounding factors (age, sex, ethnicity et al.), the cross-lagged path coefficient from baseline BMI to follow-up TyG (ρ2 = 0.135, P < 0.001) was significantly greater than the path coefficient from baseline TyG to follow-up BMI (ρ1 = 0.043, P < 0.001), and P < 0.001 for the difference between ρ1 and ρ2. Furthermore, the sensitivity analyses between women and men revealed identical findings. In addition, TyG index mediation effect on BMI-hypertension was estimated to be 38.45% (P < 0.001) in total population, 25.24% in women and 57.35% in men. CONCLUSION: These results provided evidence that the temporal relationship between BMI and insulin resistance is reciprocal and a higher BMI precedes hyperinsulinemia in Chinese adults. This relationship plays an essential role in the development of hypertension, while there is a difference between women and men.
Assuntos
Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Hiperinsulinismo/epidemiologia , Hipertensão/epidemiologia , Resistência à Insulina , Obesidade/epidemiologia , Triglicerídeos/sangue , Adulto , Biomarcadores/sangue , Feminino , Disparidades nos Níveis de Saúde , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/fisiopatologia , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Prognóstico , Medição de Risco , Fatores de Risco , Saúde da População Rural , Fatores Sexuais , Fatores de TempoRESUMO
BACKGROUND: To explore the potential correlation between 10-year atherosclerotic cardiovascular disease (ASCVD) risk and depressive symptoms in a general population. METHODS: A cross-sectional study involving 11,956 permanent residents of Liaoning Province in China ≥35 years of age was conducted. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9) while 10-year ASCVD risk was calculated using the tool suitable for China. RESULTS: Males had significantly higher 10-year ASCVD risk than females (14.2 ± 10.7% vs. 9.3 ± 9.1%; P < 0.001) but lower PHQ-9 score (2.34 ± 3.13 vs. 3.63 ± 4.02; P < 0.001). The mean PHQ-9 score increased significantly with advancing 10-year ASCVD risk category in both males (from 2.03 to 2.61; P for trend < 0.001) and females (from 3.04 to 4.61; P for trend < 0.001), and the increasing trend was more apparent in females (P < 0.001). Pearson correlation analyses showed that 10-year ASCVD risk positively correlated with PHQ-9 score in both sexes (Ps < 0.001). In multivariate linear regression analyses adjusting for confounding risk factors, the independent associations of 10-year ASCVD risk with PHQ-9 score were all significant in the total (ß = 2.61; P < 0.001), male (ß = 1.64; P = 0.001), and female subjects (ß = 3.71; P < 0.001). Further, the interaction analysis proved the impacts of 10-year ASCVD risk on PHQ-9 score were more apparent in females than males (Ps < 0.001). CONCLUSIONS: The 10-year ASCVD risk was positively associated with depressive symptoms in both males and females, which was more apparent in the latter. These findings provided some novel data about the value of 10-year ASCVD risk in estimating depressive symptoms.
Assuntos
Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/psicologia , Depressão/epidemiologia , Depressão/psicologia , Vigilância da População , Adulto , Idoso , China/epidemiologia , Análise por Conglomerados , Doença da Artéria Coronariana/diagnóstico , Estudos Transversais , Depressão/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Distribuição Aleatória , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Few studies investigate sex difference in stroke incidence in rural China hypertensive population. METHODS: A total of 5097 hypertensive patients aged ≥35 years (mean age, 56.3 ± 11.2 years; 43.8% men) were included in our analysis with a median follow-up 8.4 years in Fuxin county of Liaoning province in China. Cox proportional hazard models were used to analyze the association between the potential factors and incident stroke. RESULTS: We observed 501 new strokes (310 ischemic, 186 hemorrhagic, and 5 unclassified stroke) during the follow-up. The overall incidence of stroke was 1235.21 per 100,000 person-years; for men, the rates were 1652.51 and 920.80 for women. This sex difference in all stroke can be explained by approximately 25% through age, systolic blood pressure, body mass index, low-density lipoprotein-cholesterol, current smoking, current drinking, antihypertensive drugs, education and physical activity. Subgroup analysis indicated that in hemorrhagic stroke this sex difference was more remarkable (63.89% can be explained). CONCLUSIONS: The incidence of stroke was higher in men than that in women and this difference was partly explained by several traditional cardiovascular risk factors.
Assuntos
Pressão Sanguínea , Hipertensão/epidemiologia , Caracteres Sexuais , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Índice de Massa Corporal , China/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologiaRESUMO
BACKGROUND/AIMS: Many clinical and experimental studies have shown that treatment with statins could prevent myocardial hypertrophy and remodeling induced by hypertension and myocardial infarction. But the molecular mechanism was not clear. We aimed to investigate the beneficial effects of atorvastatin on hypertension-induced myocardial hypertrophy and remodeling in spontaneously hypertensive rats (SHR) with the hope of revealing other potential mechanisms or target pathways to interpret the pleiotropic effects of atorvastatin on myocardial hypertrophy. METHODS: The male and age-matched animals were randomly divided into three groups: control group (8 WKY), SHR (8 rats) and intervention group (8 SHR). The SHR in intervention group were administered by oral gavage with atorvastatin (suspension in distilled water, 10 mg/Kg once a day) for 6 weeks, and the other two groups were administered by gavage with equal quantity distilled water. Blood pressure of rats was measured every weeks using a standard tail cuff sphygmomanometer. Left ventricular (LV) dimensions were measured from short-axis views of LV under M-mode tracings using Doppler echocardiograph. Cardiomyocyte apoptosis was assessed by the TUNEL assay. The protein expression of C/EBPß, PGC-1α and UCP3 were detected by immunohistochemistry or Western blot analysis. RESULTS: At the age of 16 weeks, the mean arterial pressure of rats in three groups were 103.6±6.1, 151.8±12.5 and 159.1±6.2 mmHg respectively, and there wasn't statistically significant difference between the SHR and intervention groups. Staining with Masson's trichrome demonstrated that the increased interstitial fibrosis of LV and ventricular remodeling in the SHR group were attenuated by atorvastatin treatment. Echocardiography examination exhibited that SHR with atorvastatin treatment showed an LV wall thickness that was obviously lower than that of water-treated SHR. In hypertrophic myocardium, accompanied by increasing C/EBPß expression and the percentage of TUNEL-positive cells, the expression of Bcl-2/Bax ratio, PGC-1α and UCP3 were reduced, all of which could be abrogated by treatment with atorvastatin for 6 weeks. CONCLUSION: This study further confirmed that atorvastatin could attenuate myocardial hypertrophy and remodeling in SHR by inhibiting apoptosis and reversing changes in mitochondrial metabolism. The C/EBPß/PGC-1α/UCP3 signaling pathway might also be important for elucidating the beneficial pleiotropic effects of atorvastatin on myocardial hypertrophy.
Assuntos
Atorvastatina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/patologia , Transdução de Sinais/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Atorvastatina/uso terapêutico , Fator Natriurético Atrial/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Ecocardiografia , Hipertensão/complicações , Hipertrofia/diagnóstico por imagem , Hipertrofia/tratamento farmacológico , Hipertrofia/etiologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Proteína Desacopladora 3/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: Various anthropometric indices can be used to estimate obesity, and it is important to determine which one is the best in predicting the risk of coronary heart disease (CHD) and to define the optimal cut-off point for the best index. METHODS: This cross-sectional study investigated a consecutive sample of 11,247 adults, who had lived in rural areas of China and were older than 35 years of age. Eight obesity indices, including the body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), abdominal volume index (AVI), body adiposity index (BAI), body roundness index (BRI) and a body shape index (ABSI) were investigated. The risk of CHD was evaluated by the 10-year coronary event risk (Framingham risk score). Receiver operating characteristic (ROC) curve analyses were used to evaluate the predictive ability of the obesity indices for CHD risk. RESULTS: Of the whole population, 3636 (32.32%) participants had a risk score higher than 10%. Those who suffered medium or high CHD risk were more likely to have higher mean anthropometric indices, except for BMI in males. In the multivariate-adjusted logistic regression, all these anthropometric measurements were statistically associated with CHD risk in males. After adjusting for all the possible confounders, these anthropometric measurements, except for ABSI, remained as independent indicators of CHD risk in females. According to the ROC analyses, ABSI provided the largest area under the curve (AUC) value in males, and BMI showed the lowest AUC value, with AUC varying from 0.52 to 0.60. WHtR and BRI provided the largest AUC value in female, and similarly, BMI showed the lowest AUC value, with AUC varying from 0.59 to 0.70. The optimal cut-off values were as follows: WHtR (females: 0.54), BRI (females: 4.21), and ABSI (males: 0.078). CONCLUSIONS: ABSI was the best anthropometric index for estimating CHD risk in males, and WHtR and BRI were the best indicators in females. Males should maintain an ABSI of less than 0.078, and females should maintain a WHtR of less than 0.54 or a BRI of less than 4.21.
Assuntos
Antropometria/métodos , Doença das Coronárias/epidemiologia , Obesidade/diagnóstico , Adulto , Área Sob a Curva , Distribuição de Qui-Quadrado , China/epidemiologia , Doença das Coronárias/diagnóstico , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/epidemiologia , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Saúde da População Rural , Fatores SexuaisRESUMO
BACKGROUND: Many previous clinical studies have reported that prolongation of the QT interval corrected for heart rate (QTc) is associated with an increased risk of sudden cardiac death and all-cause mortality. This study aimed to explore associations between serum electrolytes and QTc prolongation in the north-eastern Chinese rural general population. METHODS: We performed a cross-sectional study including 10,334 (4820 men and 5514 women) from the general population aged ≥35 years in the Liaoning Province from 2012 to 2013. Anthropometric measurements, laboratory examinations and self-reported lifestyle factor information, echocardiography and electrocardiogram were collected by trained personnel. The associations between serum electrolytes and QTc prolongation were tested using multiple linear regression and logistic regression analyses. RESULTS: The mean QTc interval were 415.6 ± 18.8 and 470.1 ± 23.1 ms in normal group and QTc prolongation group respectively. The prevalence of QTc prolongation increased significantly with a decrease in serum potassium and an increase in magnesium. Stepwise multiple linear regression showed that age, hypertension, waist circumference were prominently positive associated with QTc interval both in male and female population. But serum potassium was significantly inversely associated with QTc interval. Serum magnesium and calcium also showed a positive relationship with QTc interval. Furthermore, multiple logistic regression found that lower quartile of serum potassium had higher risk for QTc prolongation, especially in female population (Q2 vs. Q4: OR: 1.54, 95%CI: 1.01-2.35; Q1 vs. Q4: OR: 2.02, 95%CI: 1.36-3.01). In addition, the higher serum magnesium increased the risk of QTc prolongation, which was significantly only in male population. CONCLUSIONS: In present Chinese rural general population, even with normal range, a decrease in serum potassium and an increase in serum magnesium are important risk factors for QTc prolongation.
Assuntos
Potenciais de Ação , Arritmias Cardíacas/sangue , Arritmias Cardíacas/fisiopatologia , Eletrólitos/sangue , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Adulto , Idoso , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Biomarcadores/sangue , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Saúde da População Rural , Fatores Sexuais , Fatores de TempoRESUMO
The aim of this article was to explore the link between postmenopausal status according to years since menopause (YSM) and the prevalence of metabolic syndrome (MetS). This survey was conducted from January 2012 to August 2013. A total of 6022 women (3511, 58.3% were post-menopause) from Rural Northeast China were randomly selected and examined. The prevalence of the MetS was significantly higher in postmenopausal women (Post-MW) than in premenopausal women (Pre-MW) (55.0% vs. 33.1%, p .001). The risk for MetS in Post-MW increased with the number of YSM, reaching the peak level in the 5- to 9-year group (OR, 1.55; 95% CI, 1.23-1.96), and then decreased. The 5- to 9-year group had the highest risk of high glucose (OR, 1.48; 95% CI, 1.20-1.83) and high triglycerides (adjusted OR, 1.92; 95% CI, 1.53-2.41) whereas the risk for abdominal obesity, high BP, and low HDL-C was not significantly associated with the number of YSM. These findings suggested that, in China, Post-MW with 5-9 YSMs had the highest risk of MetS. YSM can be a useful screening tool to identify women at high risk for MetS.
Assuntos
Menopausa , Síndrome Metabólica/epidemiologia , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , População RuralRESUMO
Previous evidences suggested that atorvastatin not only reduced blood lipids but also reduced myocardial hypertrophy and remodeling. And it was reported that C/EBPß (CCAAT/enhancer-binding protein ß) played a pivotal role both in the physiologic and pathological cardiac hypertrophy. However, it has not been reported before whether this signaling pathway of C/EBPß participates in protective effect of atorvastatin for hypertrophy cardiomyocytes. In present study, We found that overexpression of C/EBPß significantly abrogated the effect of atorvastatin on increasing Bcl-2/Bax and PGC-1α while the early and late apoptosis rate increased and mitochondrial membrane potential (MMP) was reduced. In conclusion, we further identified the protective effect of atorvastatin on hypertrophic cardiomyocytes induced by Angiotensin II by rescuing the MMP and inhibiting apoptosis, which might be at least partly attributed to down-regulation of C/EBPß. And C/EBPß might be a new target to rescue mitochondrion function and apoptosis in pathological cardiac hypertrophy.
Assuntos
Angiotensina II/farmacologia , Antagonistas de Receptores de Angiotensina/farmacologia , Anticolesterolemiantes/farmacologia , Atorvastatina/farmacologia , Proteína beta Intensificadora de Ligação a CCAAT/genética , Miócitos Cardíacos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Linhagem Celular , Regulação da Expressão Gênica , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Transdução de Sinais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Little is known about the relationship between homocysteine (Hcy) levels and the QT interval. We examined the association of different Hcy levels with corrected QT (QTc) intervals in a general population. METHODS: Plasma levels of Hcy were assessed in a population-based study of 7002 participants 35 years of age and older from 2012 to 2013. Twelve-lead ECGs were performed on all participants and analyzed automatically. RESULTS: The distribution of Hcy levels was determined for an entire population after the data were grouped into quartiles (Q1: <=11.1umol/L; Q2: 11.1-13.8umol/L; Q3: 13.8-18.2 umol/L; Q4 > 18.2 umol/L). The mean value of the QTc interval in each quartile was 433.2 ± 23.8 ms, 430.0 ± 24.6 ms, 429.2 ± 24.5 ms and 430.6 ± 25.7 ms. Multiple logistic regression analyses showed that, compared with the second quartile, and after fully adjusting for potential confounding factors, the odds for QTc > 440 ms in the first and fourth quartile increased (P < 0.05), (OR: 1.23, 95% CI: 1.05-1.43 for Q1; OR: 1.40, 95% CI: 1.19-1.65 for Q4). CONCLUSIONS: QTc interval was associated with the Hcy level in this general population.
Assuntos
Arritmias Cardíacas/sangue , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , Potenciais de Ação , Adulto , Idoso , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Biomarcadores/sangue , China/epidemiologia , Eletrocardiografia , Feminino , Humanos , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: To investigate the association between CHADS2 score, depressive symptoms, and quality of life in a large general population from China. METHODS: A cross-sectional study of 11,956 permanent residents of Liaoning Province in China ≥ 35 years of age was conducted between January and August 2013 (response rate 85.3%). All participants completed a questionnaire, had a physical examination, and underwent blood examination. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9), while the quality of life (QoL) was measured using the World Health Organization Quality of Life Brief Scale (WHOQOL-BREF). RESULTS: With increasing CHADS2 score, the prevalence of depressive symptoms increased from 4.9 to 27.8% (P < 0.001), and all scores of WHOQOL-BREF decreased significantly (all Ps < 0.001). After adjusting for confounding risk factors, subjects with CHADS2 score ≥ 3 had higher risk of depressive symptoms than those with CHADS2 score = 0 (all Ps < 0.05). Also, CHADS2 score was negatively associated with all scores of WHOQOL-BREF (all Ps < 0.001). Furthermore, subjects with any item in CHADS2 had higher prevalence of depressive symptoms (all Ps < 0.001). Heart failure and stroke remained independently associated with depressive symptoms after adjusting for confounding risk factors and other items (Ps < 0.001), while heart failure, age ≥ 75 years, diabetes mellitus, and stroke were all independently negatively associated with the total score of WHOQOL-BREF (all Ps < 0.05). CONCLUSIONS: The CHADS2 score is significantly associated with depressive symptoms and impaired quality of life in the general population.
Assuntos
Depressão/diagnóstico , Qualidade de Vida/psicologia , Inquéritos e Questionários , Adulto , Idoso , China , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Till now, no evidence illustrates the prevalence and predictors of metabolically healthy obesity (MHO) in rural areas of China. The objective of this study was, firstly, to examine the prevalence of MHO in rural areas of China, and identify contributing determinants of MHO, Secondly, to comprehensively investigate to the different characteristics between MHO and metabolically unhealthy obesity (MUO). We conducted a population-based cross-sectional study of 2037 participants with obesity in rural Liaoning Province during 2012-2013. Obesity was defined as BMI ≥28 kg/m2 and metabolically healthy was defined as not having the metabolic syndrome. The prevalence of MHO was 23.1%, and significantly decreased with advancing age in female group. However there was no significant tendency with advancing age in male group. Independent determinant factors for MHO were age <55 years (odds ratio [OR] 1.659; p = .001), non-current smoking (OR 1.397; p = .038), pre-menopause (OR 1.648; p = .030) and non-hyperuricemia (OR 2.317; p < .001), whereas race, gender, diet score, current drinking, marriage, sleep duration, hyperhomocysteinemia, levels of physical activity, annual income and educational status were not significant contributors. In conclusion, we found that age <55 years, non-current smoking, pre-menopause and non-hyperuricemia were identified as independent determinant factors for MHO in this population.