TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.

Risk Factors, Use of Preventive Drugs, and Cardiovascular Events in Diabetes Mellitus: The PURE Türkiye Cohort.

BACKGROUND: The risk of cardiovascular disease is correlated with the frequency and control of associated risk factors in diabetes mellitus and may vary according to country. We evaluated risk factors for cardiovascular disease, cardiovascular events, and the use of preventive medications in patients with diabetes mellitus using the Prospective Urban and Rural Epidemiological Türkiye cohort. METHODS: Patients with diabetes mellitus versus without diabetes mellitus were compared for risk factors, cardioprotective drugs (angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists, statins, and antiplatelets), and cardiovascular events. The primary outcome was major cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, or heart failure). RESULTS: Among 4041 participants, 549 (13.6%) had diabetes mellitus. The mean age (54.8 ± 8.4 vs. 49.3 ± 9.0 years, P <.001) and proportion of women (65.4% vs. 59.9%, P =.014) were higher in diabetics compared with non-diabetics. Hypertension, history of coronary heart disease, and use of statin, antiplatelets, and angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists were more common in diabetics; however, the use of these medications at baseline was lower than optimal even in patients with diabetes mellitus and concomitant coronary heart disease (statin 31.2%, antiplatelets 46.9%, and angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists 54.7%). During 11.5 years of follow-up, major cardiovascular events occurred in 288 (7.1%) patients, and the risk was higher in diabetics [hazard ratio (95% confidence interval) 1.71 (1.30-2.24); P <.001]. The increase in the risk of future events was comparable for those with diabetes mellitus alone without cardiovascular disease [hazard ratio 1.62 (1.20-2.20)] versus those with cardiovascular disease alone without diabetes mellitus [hazard ratio 1.31 (0.83-2.07)] and was additive in those with both conditions [hazard ratio 2.79 (1.65-4.69)]. The risk of major coronary events (myocardial infarction, angina, percutaneous, or surgical coronary intervention) was also higher in diabetes mellitus [hazard ratio 1.64 (1.26-2.15); P <.001]. CONCLUSION: Patients with diabetes mellitus have a higher risk of major cardiovascular events, and the risk is comparable to that observed in those with cardiovascular disease but no diabetes mellitus. The use of preventive medicines for cardiovascular diseases is disturbingly low in diabetics.

Comparison of frequency of silent cerebral infarction as assessed by serum neuron specific enolase in patients with non-valvular atrial fibrillation: Warfarin versus direct oral anticoagulant.

BACKGROUND: Cerebral infarction in patients with atrial fibrillation (AF) may clinically vary from being silent to catastrophic. Silent cerebral infarction (SCI) is the neuronal injury in the absence of clinically appearent stroke or transient ischaemic attack. Serum neuron specific enolase (NSE) is suggested to be a valid surrogate biomarker that allows to detect recent neuronal injury. We aimed to evaluate the incidence of recent SCI by positive NSE levels in patients with non-valvular AF (NVAF) on oral anticoagulants. METHODS: Blood samples for NSE were collected from 197 consecutive NVAF patients. NSE levels of greater than 12 ng/ml was considered as positive and suggestive of SCI. RESULTS: Patients were mainly female with a mean age of 69 years. Ninety-eight of them (49.7%) were taking warfarin. Mean INR level was 2.3 ± 0.9. Mean CHA2DS2-VASc score of the study population was 3.5 ± 1.5. Seventy-two patients (36.5%) were found to have NSE elevation. They were more likely to have history of chronic heart failure and previous stroke/TIA. Increased left atrial diameter and higher CHA2DS2-VASc were other factors associated with SCI. Patients on DOACs and patients taking aspirin on top of oral anticoagulant treatment were less likely to have SCI. Multivariate analysis demonstrated that increased left atrial diameter (OR: 2.5; 95% CI: 1.52-4; p < 0.001) and use of warfarin (OR: 2.8; 95% CI: 1.37-5.61; p = 0.005) were detected as independent predictors of SCI. CONCLUSIONS: Our study revealed that DOACs were associated with significantly reduced SCIs compared with warfarin, probably due to more effective and consistent therapeutic level of anticoagulation.

Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective cohort study.

BACKGROUND: The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development. METHODS: We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries. FINDINGS: During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; pinteraction=0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; pinteraction=0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; pinteraction=0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; pinteraction=0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; pinteraction <0·0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2·95; 2·25-3·87; pinteraction <0·0001), but not of cardiovascular diseases or mortality. INTERPRETATION: The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Lipid Modification to Reduce Cardiovascular Risk in Secondary Prevention Patients with Special Emphasis on PCSK9 Inhibitor Requirement: An Analysis Based on Delphi Panel Approach.

OBJECTIVE: The aim of this study is to analyze the low-density lipoprotein cholesterol-lowering therapies in secondary prevention patients by analyzing their plasma low-density lipoprotein cholesterol levels, current treatment, considering their inadequate response to medications (as defined in current guidelines), and the requirement for a protein convertase subtilisin/kexin type 9 inhibitor. METHODS: Delphi panel is used to seek expert consensus of experienced 12 cardiologists. A questionnaire consisting of 6 main questions is used to reflect the opinion of the expert panelists on the practices of low-density lipoprotein cholesterol-lowering therapies of patients with high and very high cardiovascular risk. Patients with atherosclerotic cardiovascular disease are covered in this present analysis. RESULTS: According to expert opinion data, 18.6% of the patient population with atherosclerotic cardiovascular disease is estimated to have experienced recurrent vascular events. The current treatment of the patient population is 39.7% on high dose, 36.9% on low/moderate dose of statin, 13.1% on maximum tolerated dose statin+ezetimibe, and 1.2% on maximum tolerated dose statin+ezetimibe+protein convertase subtilisin/kexin type 9 inhibitor. The percentage of atherosclerotic cardiovascular disease patients with inadequate treatment response is estimated to be 20.2% in those using "maximum tolerated dose statin+ezetimibe." The proportion of patients who will need to be treated with a protein convertase subtilisin/kexin type 9 inhibitor increases as their low-density lipoprotein cholesterol levels rises from 9.1% in 70-99 mg/dL to 50.8% in ≥160 mg/dL for these patients. CONCLUSION: According to expert opinion, although a substantial proportion of patients with secondary prevention have not achieved low-density lipoprotein cholesterol goals, the use of protein convertase subtilisin/kexin type 9 inhibitors is very low. Since the questionnaire subject to panel discussion did not include any question elaborating the issue, the discrepancy between the recommendation of the related guidelines and Turkish practice needs further studies for the explanation.

Psychosocial Risk Factors and Cardiovascular Disease and Death in a Population-Based Cohort From 21 Low-, Middle-, and High-Income Countries.

Importance: Stress may increase the risk of cardiovascular disease (CVD). Most studies on stress and CVD have been conducted in high-income Western countries, but whether stress is associated with CVD in other settings has been less well studied. Objective: To investigate the association of a composite measure of psychosocial stress and the development of CVD events and mortality in a large prospective study involving populations from 21 high-, middle-, and low-income countries across 5 continents. Design, Setting, and Participants: This population-based cohort study used data from the Prospective Urban Rural Epidemiology study, collected between January 2003 and March 2021. Participants included individuals aged 35 to 70 years living in 21 low-, middle-, and high-income countries. Data were analyzed from April 8 to June 15, 2021. Exposures: All participants were assessed on a composite measure of psychosocial stress assessed at study entry using brief questionnaires concerning stress at work and home, major life events, and financial stress. Main Outcomes and Measures: The outcomes of interest were stroke, major coronary heart disease (CHD), CVD, and all-cause mortality. Results: A total of 118 706 participants (mean [SD] age 50.4 [9.6] years; 69 842 [58.8%] women and 48 864 [41.2%] men) without prior CVD and with complete baseline and follow-up data were included. Of these, 8699 participants (7.3%) reported high stress, 21 797 participants (18.4%) reported moderate stress, 34 958 participants (29.4%) reported low stress, and 53 252 participants (44.8%) reported no stress. High stress, compared with no stress, was more likely with younger age (mean [SD] age, 48.9 [8.9] years vs 51.1 [9.8] years), abdominal obesity (2981 participants [34.3%] vs 10 599 participants [19.9%]), current smoking (2319 participants [26.7%] vs 10 477 participants [19.7%]) and former smoking (1571 participants [18.1%] vs 3978 participants [7.5%]), alcohol use (4222 participants [48.5%] vs 13 222 participants [24.8%]), and family history of CVD (5435 participants [62.5%] vs 20 255 participants [38.0%]). During a median (IQR) follow-up of 10.2 (8.6-11.9) years, a total of 7248 deaths occurred. During the course of follow-up, there were 5934 CVD events, 4107 CHD events, and 2880 stroke events. Compared with no stress and after adjustment for age, sex, education, marital status, location, abdominal obesity, hypertension, smoking, diabetes, and family history of CVD, as the level of stress increased, there were increases in risk of death (low stress: hazard ratio [HR], 1.09 [95% CI, 1.03-1.16]; high stress: 1.17 [95% CI, 1.06-1.29]) and CHD (low stress: HR, 1.09 [95% CI, 1.01-1.18]; high stress: HR, 1.24 [95% CI, 1.08-1.42]). High stress, but not low or moderate stress, was associated with CVD (HR, 1.22 [95% CI, 1.08-1.37]) and stroke (HR, 1.30 [95% CI, 1.09-1.56]) after adjustment. Conclusions and Relevance: This cohort study found that higher psychosocial stress, measured as a composite score of self-perceived stress, life events, and financial stress, was significantly associated with mortality as well as with CVD, CHD, and stroke events.

Relationship between silent cerebral infarcts and quality of anticoagulation in patients with prosthetic mitral valves.

OBJECTIVE: Although patients with prosthetic heart valves have an increased risk of clinically overt cerebrovascular events, evidence for the risk of silent cerebral infarction (SCI) is scarce. Serum neuron-specific enolase (NSE) is suggested to be a valid biomarker that allows for the quantification of the degree of neuronal injury. We aimed to assess whether NSE is elevated as a marker of recent SCI in patients with a prosthetic mitral valve. METHODS: We measured the NSE levels in 103 patients with a prosthetic mitral valve (PMV), admitted to our outpatient clinics for routine evaluation. International normalized ratio (INR) and time in target therapeutic range (TTR) were noted as anticoagulation quality measures. RESULTS: Most of the patients were females (58%), and a mean age was 65 years. NSE values of >12 ng/mL, suggesting a recent SCI, was detected in 25 patients (24%). NSE was negatively correlated with admission INR (r=-0.307, p=0.002). Multivariate analyses demonstrated subtherapeutic INR (INR <2.5) and suboptimal TTR as independent predictors of SCI [odds ratio (OR) 5.420; 95% confidence interval (CI) 1.589 to 18.483; p=0.007, and OR 4.149; 95% CI 1.019 to 16.949; p=0.047, respectively]. Being a current smoker (OR 10.798; 95% CI 2.520 to 46.272; p=0.001), large left atrium (OR 6.763; 95% CI 2.253 to 20.302; p=0.001), and not using aspirin (OR 10.526; 95% CI 1.298 to 83.333; p=0.027) were other independent predictors. CONCLUSION: Our data suggest that silent brain infarcts are very prevalent among patients with a PMV, as one fourth of them had the event during their routine outpatient visit. Poor quality of anticoagulation partly explains the increased prevalence.

Associations of Fish Consumption With Risk of Cardiovascular Disease and Mortality Among Individuals With or Without Vascular Disease From 58 Countries.

Importance: Cohort studies report inconsistent associations between fish consumption, a major source of long-chain ω-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown. Objective: To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease. Design, Setting, and Participants: This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies-147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. This analysis was conducted from January to June 2020. Exposures: Fish consumption was recorded using validated food frequency questionnaires. In 1 of the cohorts with vascular disease, a separate qualitative food frequency questionnaire was used to assess intake of individual types of fish. Main Outcomes and Measures: Mortality and major CVD events (including myocardial infarction, stroke, congestive heart failure, or sudden death). Results: Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] male) were included in the present analysis. During 9.1 years of follow-up in PURE, compared with little or no fish intake (≤50 g/mo), an intake of 350 g/wk or more was not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 0.88-1.05). By contrast, in the 3 cohorts of patients with vascular disease, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/wk (or approximately 2 servings/wk) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher. Fish with higher amounts of ω-3 fatty acids were strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other fish were neutral (collected in 1 cohort of patients with vascular disease). The association between fish intake and each outcome varied by CVD status, with a lower risk found among patients with vascular disease but not in general populations (for major CVD, I2 = 82.6 [P = .02]; for death, I2 = 90.8 [P = .001]). Conclusions and Relevance: Findings of this pooled analysis of 4 cohort studies indicated that a minimal fish intake of 175 g (approximately 2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease.

Availability and affordability of medicines and cardiovascular outcomes in 21 high-income, middle-income and low-income countries.

OBJECTIVES: We aimed to examine the relationship between access to medicine for cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs) among people at high risk of CVD in high-income countries (HICs), upper and lower middle-income countries (UMICs, LMICs) and low-income countries (LICs) participating in the Prospective Urban Rural Epidemiology (PURE) study. METHODS: We defined high CVD risk as the presence of any of the following: hypertension, coronary artery disease, stroke, smoker, diabetes or age >55 years. Availability and affordability of blood pressure lowering drugs, antiplatelets and statins were obtained from pharmacies. Participants were categorised: group 1-all three drug types were available and affordable, group 2-all three drugs were available but not affordable and group 3-all three drugs were not available. We used multivariable Cox proportional hazard models with nested clustering at country and community levels, adjusting for comorbidities, sociodemographic and economic factors. RESULTS: Of 163 466 participants, there were 93 200 with high CVD risk from 21 countries (mean age 54.7, 49% female). Of these, 44.9% were from group 1, 29.4% from group 2 and 25.7% from group 3. Compared with participants from group 1, the risk of MACEs was higher among participants in group 2 (HR 1.19, 95% CI 1.07 to 1.31), and among participants from group 3 (HR 1.25, 95% CI 1.08 to 1.50). CONCLUSION: Lower availability and affordability of essential CVD medicines were associated with higher risk of MACEs and mortality. Improving access to CVD medicines should be a key part of the strategy to lower CVD globally.

Risk of cardiovascular events in patients with metabolic syndrome: Results of a population-based prospective cohort study (PURE Turkey).

OBJECTIVE: Metabolic syndrome (MetS) includes several cardiovascular (CV) risk factors. This study aimed to assess CV risk of MetS, contribution of its components to the risk, and whether MetS provides additional risk beyond its components. METHODS: The Prospective Urban Rural Epidemiology (PURE) Turkey cohort included 3933 individuals aged between 35 and 70 years, with a median follow-up of 8.9 years. MetS was diagnosed as the presence of any of the following criteria: high blood pressure, high fasting plasma glucose, abdominal obesity, low HDL-cholesterol, or high triglycerides. The primary outcome was the composite of fatal CV events, non-fatal myocardial infarction, stroke or heart failure, adjusted for age, sex, smoking, family history of CV diseases, and LDL-cholesterol. RESULTS: The primary outcome was more common in the MetS group [178 (9.2%) vs. 70 (3.5%); corresponding incidence rate of 11.3 vs. 4.2 per 1000 person-years; log-rank p<0.001]. Each component was significantly associated with the primary outcome; however, when the components were sequentially included in the model, abdominal obesity and high triglycerides did not provide additional risk on top of the other three components. The hazard ratio for MetS for the primary outcome was 2.12 (95% confidence interval 1.59-2.81, p<0.001), and the discriminative ability (c-statistics) of the models with MetS and the components was similar. CONCLUSION: MetS increases the risk of CV events more than two-fold. High blood pressure, high fasting plasma glucose, and low HDL-cholesterol are the top three components of MetS for CV risk. MetS and its components have a similar discriminative ability for CV events.

Socioeconomic status and risk of cardiovascular disease in 20 low-income, middle-income, and high-income countries: the Prospective Urban Rural Epidemiologic (PURE) study

Background Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status­wealth and education­differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. Methods In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorized as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. (AU)

Socioeconomic status and risk of cardiovascular disease in 20 low-income, middle-income, and high-income countries: the Prospective Urban Rural Epidemiologic (PURE) study.

BACKGROUND: Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status-wealth and education-differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. METHODS: In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. FINDINGS: Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96-1·58) for high-income countries, 1·59 (1·42-1·78) in middle-income countries, and 2·23 (1·79-2·77) in low-income countries (pinteraction<0·0001). We observed similar results for all-cause mortality, with HRs of 1·50 (1·14-1·98) for high-income countries, 1·80 (1·58-2·06) in middle-income countries, and 2·76 (2·29-3·31) in low-income countries (pinteraction<0·0001). By contrast, we found no or weak associations between wealth and these two outcomes. Differences in outcomes between educational groups were not explained by differences in risk factors, which decreased as the level of education increased in high-income countries, but increased as the level of education increased in low-income countries (pinteraction<0·0001). Medical care (eg, management of hypertension, diabetes, and secondary prevention) seemed to play an important part in adverse cardiovascular disease outcomes because such care is likely to be poorer in people with the lowest levels of education compared to those with higher levels of education in low-income countries; however, we observed less marked differences in care based on level of education in middle-income countries and no or minor differences in high-income countries. INTERPRETATION: Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Relation of Acute Decompensated Heart Failure to Silent Cerebral Infarcts in Patients With Reduced Left Ventricular Ejection Fraction.

Heart failure (HF) is a prothrombotic state with increased rate of thromboembolic events. Magnetic resonance imaging studies demonstrated increased rate of silent cerebral infarcts (SCI) in this patient group and SCIs were shown lead to dementia, cognitive decline, and depression. We aimed to show acute decompensated phase is associated with increased rate of recent SCI in reduced ejection fraction HF patients. HF patients with sinus rhythm hospitalized for acute decompensation were studied. Neuron specific enolase (NSE), a sensitive neuronal ischemia marker, was used to detect recent SCI. Decompensated and compensated phase blood samples for NSE were collected on the day of admission and on the third day of compensation, respectively. One hundred and forty seven patients with mean age of 72 were studied. There were significantly more patients with positive NSE levels at decompensated state (29% vs 4%, p <0.001). Multivariate predictors for recent SCI were smoking, new onset atrial fibrillation, spontaneous echo contrast of left ventricle, and aneurysmatic apex. Statin use was found to be protective against NSE elevation. In conclusion, our data reveal that decompensated HF is significantly associated with increased levels of NSE suggestive for silent neuronal injury.

Urinary sodium excretion, blood pressure, cardiovascular disease, and mortality: a community-level prospective epidemiological cohort study.

BACKGROUND: WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality. METHODS: The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all >50 participants) and cardiovascular disease and mortality in 255 communities (all >100 participants), and used individual-level data to adjust for known confounders. FINDINGS: 95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p<0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile <4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile >5·08 g/day, mean intake 5·75 g/day, >5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p<0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries. INTERPRETATION: Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate. FUNDING: Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.

Urinary sodium excretion, blood pressure, cardiovascular disease, and mortality: a community-level prospective epidemiological cohort study

BACKGROUND: WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality. METHODS: The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all >50 participants) and cardiovascular disease and mortality in 255 communities (all >100 participants), and used individual-level data to adjust for known confounders. FINDINGS: 95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p<0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile <4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile >5·08 g/day, mean intake 5·75 g/day, >5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p<0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries. INTERPRETATION: Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate.

Comparison of Frequency of Silent Cerebral Infarction After Coronary Angiography and Stenting With Transradial Versus Transfemoral Approaches.

Silent cerebral infarction (SCI) can be seen after coronary procedures. We investigated whether vascular access sites have an impact on the risk of SCI. A total of 255 consecutive patients who underwent diagnostic or interventional coronary procedures through transfemoral (n = 126 patients) or transradial (n = 129 patients) approach were evaluated. Neuron-specific enolase (NSE) levels were studied before and 12 hours after the procedure. Elevation of greater than 12 ng/ml was considered as SCI. Patients were mainly men (60%) with a mean age of 62 years. SCI was observed in 74 of 255 patients (29%). It was significantly more prevalent among transradial group. Elevation of NSE was observed in 36% of transradial group (n = 47) and 21% of the transfemoral group (n = 27) (p = 0.008). Patients with SCI were more likely to have male sexuality, hyperlipidemia, history of smoking, and previous myocardial infarction. Multivariate analysis demonstrated that patients who underwent coronary procedures through transradial approach were 2.1 times more likely to have an SCI than patients with transfemoral approach (95% confidence interval [CI] 1.205 to 3.666; p = 0.008). Other independent predictors of NSE elevation were previous myocardial infarction (odds ratio 8.6; 95% CI 4.209 to 17.572; p <0.001) and smoking history (odds ratio 7.251; 95% CI 3.855 to 13.639; p <0.001). The present study suggests that transradial coronary procedures carry higher risk of SCI when compared with transfemoral route.

Prognostic validation of a non-laboratory and a laboratory based cardiovascular disease risk score in multiple regions of the world.

OBJECTIVE: To evaluate the performance of the non-laboratory INTERHEART risk score (NL-IHRS) to predict incident cardiovascular disease (CVD) across seven major geographic regions of the world. The secondary objective was to evaluate the performance of the fasting cholesterol-based IHRS (FC-IHRS). METHODS: Using measures of discrimination and calibration, we tested the performance of the NL-IHRS (n=100 475) and FC-IHRS (n=107 863) for predicting incident CVD in a community-based, prospective study across seven geographic regions: South Asia, China, Southeast Asia, Middle East, Europe/North America, South America and Africa. CVD was defined as the composite of cardiovascular death, myocardial infarction, stroke, heart failure or coronary revascularisation. RESULTS: Mean age of the study population was 50.53 (SD 9.79) years and mean follow-up was 4.89 (SD 2.24) years. The NL-IHRS had moderate to good discrimination for incident CVD across geographic regions (concordance statistic (C-statistic) ranging from 0.64 to 0.74), although recalibration was necessary in all regions, which improved its performance in the overall cohort (increase in C-statistic from 0.69 to 0.72, p<0.001). Regional recalibration was also necessary for the FC-IHRS, which also improved its overall discrimination (increase in C-statistic from 0.71 to 0.74, p<0.001). In 85 078 participants with complete data for both scores, discrimination was only modestly better with the FC-IHRS compared with the NL-IHRS (0.74 vs 0.73, p<0.001). CONCLUSIONS: External validations of the NL-IHRS and FC-IHRS suggest that regionally recalibrated versions of both can be useful for estimating CVD risk across a diverse range of community-based populations. CVD prediction using a non-laboratory score can provide similar accuracy to laboratory-based methods.