Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study

Rosengren A., Smyth A., Rangarajan S., Ramasundarahettige C., Bangdiwala S.I., AlHabib K.F., Avezum A., Bengtsson Boström K., Chifamba J., Gulec S., Gupta R., Igumbor E.U., Iqbal R., Ismail N., Joseph P., et. al.

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.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.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

Welsh C.E., Welsh P., Jhund P., Delles C., Celis-Morales C., Lewsey J.D., Gray S., Lyall D., Iliodromiti S., Gill J.M., Sattar N., Mark P.B.

Hypertension is a risk factor for cardiovascular disease. Increased urinary sodium excretion, representing dietary sodium intake, is associated with hypertension. Low sodium intake has been associated with increased mortality in observational studies. Further studies should assess whether confounding relationships explain associations between sodium intake and outcomes. We studied UK Biobank participants (n=457 484; mean age, 56.3 years; 44.7% men) with urinary electrolytes and blood pressure data. Estimated daily urinary sodium excretion was calculated using Kawasaki formulae. We analyzed associations between sodium excretion and blood pressure in subjects without cardiovascular disease, treated hypertension, or diabetes mellitus at baseline (n=322 624). We tested relationships between sodium excretion, incidence of fatal and nonfatal cardiovascular disease, heart failure, and mortality. Subjects in higher quintiles of sodium excretion were younger, with more men and higher body mass index. There was a linear relationship between increasing urinary sodium excretion and blood pressure. During median follow-up of 6.99 years, there were 11 932 deaths (1125 cardiovascular deaths) with 10 717 nonfatal cardiovascular events. There was no relationship between quintile of sodium excretion and outcomes. These relationships were unchanged after adjustment for comorbidity or excluding subjects with events during the first 2 years follow-up. No differing risk of incident heart failure (1174 events) existed across sodium excretion quintiles. Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. No pattern of increased cardiovascular disease, heart failure, or mortality risk was demonstrated with either high or low sodium intake.

Stanaway J.D., Afshin A., Gakidou E., Lim S.S., Abate D., Abate K.H., Abbafati C., Abbasi N., Abbastabar H., Abd-Allah F., Abdela J., Abdelalim A., Abdollahpour I., Abdulkader R.S., Abebe M., et. al.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk-outcome associations.We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.In 2017, 34·1 million (95% uncertainty interval [UI] 33·3-35·0) deaths and 1·21 billion (1·14-1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6-62·4) of deaths and 48·3% (46·3-50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39-11·5) deaths and 218 million (198-237) DALYs, followed by smoking (7·10 million [6·83-7·37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6·53 million [5·23-8·23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4·72 million [2·99-6·70] deaths and 148 million [98·6-202] DALYs), and short gestation for birthweight (1·43 million [1·36-1·51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3-6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low.By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning.Bill & Melinda Gates Foundation.

Roth G.A., Abate D., Abate K.H., Abay S.M., Abbafati C., Abbasi N., Abbastabar H., Abd-Allah F., Abdela J., Abdelalim A., Abdollahpour I., Abdulkader R.S., Abebe H.T., Abebe M., Abebe Z., et. al.

Summary Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries—Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5–23·9), representing an additional 7·61 million (7·20–8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0–8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0–24·0) and the death rate by 31·8% (30·1–33·3). Total deaths from injuries increased by 2·3% (0·5–4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2–15·1) to 57·9 deaths (55·9–59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000–289 000) globally in 2007 to 352 000 (334 000–363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8–148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2–40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2–36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990—neonatal disorders, lower respiratory infections, and diarrhoeal diseases—were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Funding Bill & Melinda Gates Foundation.

Mente A., O'Donnell M., Rangarajan S., McQueen M., Dagenais G., Wielgosz A., Lear S., Ah S.T., Wei L., Diaz R., Avezum A., Lopez-Jaramillo P., Lanas F., Mony P., Szuba A., et. al.

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.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.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 (p5·08-7·49; 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

Shaddick G., Thomas M.L., Amini H., Broday D., Cohen A., Frostad J., Green A., Gumy S., Liu Y., Martin R.V., Pruss-Ustun A., Simpson D., van Donkelaar A., Brauer M.

Air pollution is a leading global disease risk factor. Tracking progress (e.g., for Sustainable Development Goals) requires accurate, spatially resolved, routinely updated exposure estimates. A Bayesian hierarchical model was developed to estimate annual average fine particle (PM2.5) concentrations at 0.1° × 0.1° spatial resolution globally for 2010-2016. The model incorporated spatially varying relationships between 6003 ground measurements from 117 countries, satellite-based estimates, and other predictors. Model coefficients indicated larger contributions from satellite-based estimates in countries with low monitor density. Within and out-of-sample cross-validation indicated improved predictions of ground measurements compared to previous (Global Burden of Disease 2013) estimates (increased within-sample R2 from 0.64 to 0.91, reduced out-of-sample, global population-weighted root mean squared error from 23 μg/m3 to 12 μg/m3). In 2016, 95% of the world's population lived in areas where ambient PM2.5 levels exceeded the World Health Organization 10 μg/m3 (annual average) guideline; 58% resided in areas above the 35 μg/m3 Interim Target-1. Global population-weighted PM2.5 concentrations were 18% higher in 2016 (51.1 μg/m3) than in 2010 (43.2 μg/m3), reflecting in particular increases in populous South Asian countries and from Saharan dust transported to West Africa. Concentrations in China were high (2016 population-weighted mean: 56.4 μg/m3) but stable during this period.

Stringhini S., Carmeli C., Jokela M., Avendaño M., Muennig P., Guida F., Ricceri F., d'Errico A., Barros H., Bochud M., Chadeau-Hyam M., Clavel-Chapelon F., Costa G., Delpierre C., Fraga S., et. al.

In 2011, WHO member states signed up to the 25 × 25 initiative, a plan to cut mortality due to non-communicable diseases by 25% by 2025. However, socioeconomic factors influencing non-communicable diseases have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to mortality and years-of-life-lost with that of the 25 × 25 conventional risk factors.We did a multicohort study and meta-analysis with individual-level data from 48 independent prospective cohort studies with information about socioeconomic status, indexed by occupational position, 25 × 25 risk factors (high alcohol intake, physical inactivity, current smoking, hypertension, diabetes, and obesity), and mortality, for a total population of 1 751 479 (54% women) from seven high-income WHO member countries. We estimated the association of socioeconomic status and the 25 × 25 risk factors with all-cause mortality and cause-specific mortality by calculating minimally adjusted and mutually adjusted hazard ratios [HR] and 95% CIs. We also estimated the population attributable fraction and the years of life lost due to suboptimal risk factors.During 26·6 million person-years at risk (mean follow-up 13·3 years [SD 6·4 years]), 310 277 participants died. HR for the 25 × 25 risk factors and mortality varied between 1·04 (95% CI 0·98-1·11) for obesity in men and 2 ·17 (2·06-2·29) for current smoking in men. Participants with low socioeconomic status had greater mortality compared with those with high socioeconomic status (HR 1·42, 95% CI 1·38-1·45 for men; 1·34, 1·28-1·39 for women); this association remained significant in mutually adjusted models that included the 25 × 25 factors (HR 1·26, 1·21-1·32, men and women combined). The population attributable fraction was highest for smoking, followed by physical inactivity then socioeconomic status. Low socioeconomic status was associated with a 2·1-year reduction in life expectancy between ages 40 and 85 years, the corresponding years-of-life-lost were 0·5 years for high alcohol intake, 0·7 years for obesity, 3·9 years for diabetes, 1·6 years for hypertension, 2·4 years for physical inactivity, and 4·8 years for current smoking.Socioeconomic circumstances, in addition to the 25 × 25 factors, should be targeted by local and global health strategies and health risk surveillance to reduce mortality.European Commission, Swiss State Secretariat for Education, Swiss National Science Foundation, the Medical Research Council, NordForsk, Portuguese Foundation for Science and Technology.

O'Donnell M.J., Chin S.L., Rangarajan S., Xavier D., Liu L., Zhang H., Rao-Melacini P., Zhang X., Pais P., Agapay S., Lopez-Jaramillo P., Damasceno A., Langhorne P., McQueen M.J., Rosengren A., et. al.

Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke.We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals.Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p

Ferguson J., Alvarez-Iglesias A., Newell J., Hinde J., O’Donnell M.

Chronic diseases tend to depend on a large number of risk factors, both environmental and genetic. Average attributable fractions were introduced by Eide and Gefeller as a way of partitioning overall disease burden into contributions from individual risk factors; this may be useful in deciding which risk factors to target in disease interventions. Here, we introduce new estimation methods for average attributable fractions that are appropriate for both case–control designs and prospective studies. Confidence intervals, derived using Monte Carlo simulation, are also described. Finally, we introduce a novel approximation for the sample average attributable fraction that will ensure a computationally tractable approach when the number of risk factors is large. An R package, [Formula: see text], implementing the methods described in this manuscript can be downloaded from the CRAN repository.

Ravnskov U., Diamond D.M., Hama R., Hamazaki T., Hammarskjöld B., Hynes N., Kendrick M., Langsjoen P.H., Malhotra A., Mascitelli L., McCully K.S., Ogushi Y., Okuyama H., Rosch P.J., Schersten T., et. al.

Objective It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.Setting, participants and outcome measures We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population.Results We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found.Conclusions High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

Skalamera J., Hummer R.A.

We documented health-related behavior clustering among US young adults and assessed the extent to which educational attainment was associated with the identified clusters.Using data from Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health), we performed latent class analysis on 8 health-related behaviors (n=14,338), documenting clustering of behavior separately by gender. Subsequently, we used multinomial logistic regression and estimated associations between educational attainment and the health-related behavior clusters.Twenty-eight percent of young women grouped into the most favorable health behavior cluster, while 22% grouped into a very high-risk cluster. A larger percentage of young men (40%) grouped into the highest risk cluster. Individuals with educational attainment at the college and advanced degree levels exhibited much lower risk of being in the unhealthy behavioral clusters than individuals with lower educational attainment, net of a range of confounders.Substantial fractions of US young adults, particularly those with less than college degrees, exhibit unhealthy behavior profiles. Efforts to improve health among young adults should focus particular attention on the clustering of poor health-related behavior, especially among individuals who have less than a college degree.

Leong D.P., Teo K.K., Rangarajan S., Lopez-Jaramillo P., Avezum A., Orlandini A., Seron P., Ahmed S.H., Rosengren A., Kelishadi R., Rahman O., Swaminathan S., Iqbal R., Gupta R., Lear S.A., et. al.

Reduced muscular strength, as measured by grip strength, has been associated with an increased risk of all-cause and cardiovascular mortality. Grip strength is appealing as a simple, quick, and inexpensive means of stratifying an individual's risk of cardiovascular death. However, the prognostic value of grip strength with respect to the number and range of populations and confounders is unknown. The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries.The Prospective Urban-Rural Epidemiology (PURE) study is a large, longitudinal population study done in 17 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years and if household members intended to stay at that address for another 4 years. Participants were assessed for grip strength, measured using a Jamar dynamometer. During a median follow-up of 4.0 years (IQR 2.9-5.1), we assessed all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, stroke, diabetes, cancer, pneumonia, hospital admission for pneumonia or chronic obstructive pulmonary disease (COPD), hospital admission for any respiratory disease (including COPD, asthma, tuberculosis, and pneumonia), injury due to fall, and fracture. Study outcomes were adjudicated using source documents by a local investigator, and a subset were adjudicated centrally.Between January, 2003, and December, 2009, a total of 142,861 participants were enrolled in the PURE study, of whom 139,691 with known vital status were included in the analysis. During a median follow-up of 4.0 years (IQR 2.9-5.1), 3379 (2%) of 139,691 participants died. After adjustment, the association between grip strength and each outcome, with the exceptions of cancer and hospital admission due to respiratory illness, was similar across country-income strata. Grip strength was inversely associated with all-cause mortality (hazard ratio per 5 kg reduction in grip strength 1.16, 95% CI 1.13-1.20; p

Mente A., O'Donnell M.J., Rangarajan S., McQueen M.J., Poirier P., Wielgosz A., Morrison H., Li W., Wang X., Di C., Mony P., Devanath A., Rosengren A., Oguz A., Zatonska K., et. al.

Higher levels of sodium intake are reported to be associated with higher blood pressure. Whether this relationship varies according to levels of sodium or potassium intake and in different populations is unknown.We studied 102,216 adults from 18 countries. Estimates of 24-hour sodium and potassium excretion were made from a single fasting morning urine specimen and were used as surrogates for intake. We assessed the relationship between electrolyte excretion and blood pressure, as measured with an automated device.Regression analyses showed increments of 2.11 mm Hg in systolic blood pressure and 0.78 mm Hg in diastolic blood pressure for each 1-g increment in estimated sodium excretion. The slope of this association was steeper with higher sodium intake (an increment of 2.58 mm Hg in systolic blood pressure per gram for sodium excretion >5 g per day, 1.74 mm Hg per gram for 3 to 5 g per day, and 0.74 mm Hg per gram for

O'Donnell M., Mente A., Rangarajan S., McQueen M.J., Wang X., Liu L., Yan H., Lee S.F., Mony P., Devanath A., Rosengren A., Lopez-Jaramillo P., Diaz R., Avezum A., Lanas F., et. al.

The optimal range of sodium intake for cardiovascular health is controversial.We obtained morning fasting urine samples from 101,945 persons in 17 countries and estimated 24-hour sodium and potassium excretion (used as a surrogate for intake). We examined the association between estimated urinary sodium and potassium excretion and the composite outcome of death and major cardiovascular events.The mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow-up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (≥ 7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The association between a high estimated sodium excretion and the composite outcome was strongest among participants with hypertension (P=0.02 for interaction), with an increased risk at an estimated sodium excretion of 6.00 g or more per day. As compared with the reference range, an estimated sodium excretion that was below 3.00 g per day was also associated with an increased risk of the composite outcome (odds ratio, 1.27; 95% CI, 1.12 to 1.44). As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a reduced risk of the composite outcome.In this study in which sodium intake was estimated on the basis of measured urinary excretion, an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events. (Funded by the Population Health Research Institute and others.).

Corsi D.J., Subramanian S.V., Chow C.K., McKee M., Chifamba J., Dagenais G., Diaz R., Iqbal R., Kelishadi R., Kruger A., Lanas F., López-Jaramilo P., Mony P., Mohan V., Avezum A., et. al.

Huang Y., Wang S., Tian L., Zhang X., Liu S., Zhu Z., Wang W., Shi D., He M., Shang X.

Ni M., Chen Z., Zhang J., Niu Y., Li H., Ning Y., Lin M., Liang H.

Yuan D., Zhang T., Guo C.

Zhao H., Guo M., Yang C., Xing F.

Rivadeneira J., Fuenmayor-González L., Jácome-García M., Flores-Lastra N., Delgado H., Otzen T.

Jin Y., Guo X., Cadilhac D.A., Qiu Y., Wang S., Zhang Z., Zhang L., Lin B.

Płoński A., Krupa A., Pawlak D., Sokołowska K., Sieklucka B., Gabriel M., Płoński A.F., Głowiński J., Pawlak K.

van der Linden E.L., Hoevenaar-Blom M., Beune E., Nkansah Darko S., Twumasi Ankrah S., Meeks K.A., Chilunga F., Hayfron-Benjamin C., Henneman P., van den Born B., Owusu Dabo E., Agyemang C.

Zhu Y., Yao T., Tian L., Zhang Y., Ke Q.

Bernardes de Figueiredo Oliveira G., Belo Nunes R.A., Bassolli de Oliveira Alves L., Miranda de Menezes Neves P.D., Hamamoto Sato V.A., Kamada Triboni A.H., Alves de Oliveira Júnior H., Raupp da Rosa P., Díaz M.L., Lopez-Jaramillo J.P., Lanas F., Joseph P., Avezum Á.

Chang W., Zeng Q., Zhou B.

Ali S.A., Vinding N.E., Butt J.H., Krøll J., Larsson J.E., Schou M., Fosbøl E.L., Løgstrup B.B., Schjødt I., Jhund P.S., Køber L., Gustafsson F., Sattar N., McMurray J.J., Kristensen S.L.

Diaz-Arocutipa C., Salguero-Bodes R., Juárez V., Martín-Asenjo R., Valenzuela-Rodriguez G., Torres-Valencia J., Navarro P.R., Pariona M., Vicent L.

Qin H., Tromp J., ter Maaten J.M., Voordes G.H., van Essen B.J., André de la Rambelje M., van der Hoef C.C., Santema B.T., Lam C.S., Voors A.A.

Adams S.C., Rivera-Theurel F., Scott J.M., Nadler M.B., Foulkes S., Leong D., Nilsen T., Porter C., Haykowsky M., Abdel-Qadir H., Hull S.C., Iyengar N.M., Dieli-Conwright C.M., Dent S.F., Howden E.J.

Abstract The aim of this whitepaper is to review the current state of the literature on the effects of cardio-oncology rehabilitation and exercise (CORE) programmes and provide a roadmap for improving the evidence-based to support the implementation of CORE. There is an urgent need to reinforce and extend the evidence informing the cardiovascular care of cancer survivors. CORE is an attractive model that is potentially scalable to improve the cardiovascular health of cancer survivors as it leverages many of the existing frameworks developed through decades of delivery of cardiac rehabilitation. However, there are several challenges within this burgeoning field, including limited evidence of the efficacy of this approach in patients with cancer. In this paper, a multidisciplinary team of international experts highlights priorities for future research in this field and recommends standards for the conduct of research.