Renata Micha

Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Dariush Mozaffarian and colleagues conduct a systematic review and meta-analysis to investigate the effect of consuming polyunsaturated fats in place of saturated fats for lowering the risk of coronary heart disease.

Red and Processed Meat Consumption and Risk of Incident Coronary Heart Disease, Stroke, and Diabetes Mellitus A Systematic Review and Meta-Analysis

Background— Meat consumption is inconsistently associated with development of coronary heart disease (CHD), stroke, and diabetes mellitus, limiting quantitative recommendations for consumption levels. Effects of meat intake on these different outcomes, as well as of red versus processed meat, may also vary. Methods and Results— We performed a systematic review and meta-analysis of evidence for relationships of red (unprocessed), processed, and total meat consumption with incident CHD, stroke, and diabetes mellitus. We searched for any cohort study, case-control study, or randomized trial that assessed these exposures and outcomes in generally healthy adults. Of 1598 identified abstracts, 20 studies met inclusion criteria, including 17 prospective cohorts and 3 case-control studies. All data were abstracted independently in duplicate. Random-effects generalized least squares models for trend estimation were used to derive pooled dose-response estimates. The 20 studies included 1 218 380 individuals and 23 889 CHD, 2280 stroke, and 10 797 diabetes mellitus cases. Red meat intake was not associated with CHD (n=4 studies; relative risk per 100-g serving per day=1.00; 95% confidence interval, 0.81 to 1.23; P for heterogeneity=0.36) or diabetes mellitus (n=5; relative risk=1.16; 95% confidence interval, 0.92 to 1.46; P=0.25). Conversely, processed meat intake was associated with 42% higher risk of CHD (n=5; relative risk per 50-g serving per day=1.42; 95% confidence interval, 1.07 to 1.89; P=0.04) and 19% higher risk of diabetes mellitus (n=7; relative risk=1.19; 95% confidence interval, 1.11 to 1.27; P<0.001). Associations were intermediate for total meat intake. Consumption of red and processed meat were not associated with stroke, but only 3 studies evaluated these relationships. Conclusions— Consumption of processed meats, but not red meats, is associated with higher incidence of CHD and diabetes mellitus. These results highlight the need for better understanding of potential mechanisms of effects and for particular focus on processed meats for dietary and policy recommendations.

Saturated Fat and Cardiometabolic Risk Factors, Coronary Heart Disease, Stroke, and Diabetes: a Fresh Look at the Evidence

Dietary and policy recommendations frequently focus on reducing saturated fatty acid consumption for improving cardiometabolic health, based largely on ecologic and animal studies. Recent advances in nutritional science now allow assessment of critical questions about health effects of saturated fatty acids (SFA). We reviewed the evidence from randomized controlled trials (RCTs) of lipid and non-lipid risk factors, prospective cohort studies of disease endpoints, and RCTs of disease endpoints for cardiometabolic effects of SFA consumption in humans, including whether effects vary depending on specific SFA chain-length; on the replacement nutrient; or on disease outcomes evaluated. Compared with carbohydrate, the TC:HDL-C ratio is nonsignificantly affected by consumption of myristic or palmitic acid, is nonsignificantly decreased by stearic acid, and is significantly decreased by lauric acid. However, insufficient evidence exists for different chain-length-specific effects on other risk pathways or, more importantly, disease endpoints. Based on consistent evidence from human studies, replacing SFA with polyunsaturated fat modestly lowers coronary heart disease risk, with ~10% risk reduction for a 5% energy substitution; whereas replacing SFA with carbohydrate has no benefit and replacing SFA with monounsaturated fat has uncertain effects. Evidence for the effects of SFA consumption on vascular function, insulin resistance, diabetes, and stroke is mixed, with many studies showing no clear effects, highlighting a need for further investigation of these endpoints. Public health emphasis on reducing SFA consumption without considering the replacement nutrient or, more importantly, the many other food-based risk factors for cardiometabolic disease is unlikely to produce substantial intended benefits.

Systematic Review and Meta-analysis of Methotrexate Use and Risk of Cardiovascular Disease

Inflammation predicts risk for cardiovascular disease (CVD) events, but the relation of drugs that directly target inflammation with CVD risk is not established. Methotrexate is a disease-modifying antirheumatic drug broadly used for the treatment of chronic inflammatory disorders. A systematic review and meta-analysis of evidence of relations of methotrexate with CVD occurrence were performed. Cohorts, case-control studies, and randomized trials were included if they reported associations between methotrexate and CVD risk. Inclusions and exclusions were independently adjudicated, and all data were extracted in duplicate. Pooled effects were calculated using inverse variance-weighted meta-analysis. Of 694 identified publications, 10 observational studies in which methotrexate was administered in patients with rheumatoid arthritis, psoriasis, or polyarthritis met the inclusion criteria. Methotrexate was associated with a 21% lower risk for total CVD (n = 10 studies, 95% confidence interval [CI] 0.73 to 0.87, p <0.001) and an 18% lower risk for myocardial infarction (n = 5, 95% CI 0.71 to 0.96, p = 0.01), without evidence for statistical between-study heterogeneity (p = 0.30 and p = 0.33, respectively). Among prespecified sources of heterogeneity explored, stronger associations were observed in studies that adjusted for underlying disease severity (relative risk 0.64, 95% CI 0.43 to 0.96, p <0.01) and for other concomitant medication (relative risk 0.73, 95% CI 0.63 to 0.84, p <0.001). Publication bias was potentially evident (funnel plot, Beggs test, p = 0.06); excluding studies with extreme risk estimates did not, however, alter results (relative risk 0.81, 95% CI 0.74 to 0.89). In conclusion, methotrexate use is associated with a lower risk for CVD in patients with chronic inflammation. These findings suggest that a direct treatment of inflammation may reduce CVD risk.

Global, regional and national sodium intakes in 1990 and 2010: a systematic analysis of 24 h urinary sodium excretion and dietary surveys worldwide.

Objectives To estimate global, regional (21 regions) and national (187 countries) sodium intakes in adults in 1990 and 2010. Design Bayesian hierarchical modelling using all identifiable primary sources. Data sources and eligibility We searched and obtained published and unpublished data from 142 surveys of 24 h urinary sodium and 103 of dietary sodium conducted between 1980 and 2010 across 66 countries. Dietary estimates were converted to urine equivalents based on 79 pairs of dual measurements. Modelling methods Bayesian hierarchical modelling used survey data and their characteristics to estimate mean sodium intake, by sex, 5 years age group and associated uncertainty for persons aged 20+ in 187 countries in 1990 and 2010. Country-level covariates were national income/person and composition of food supplies. Main outcome measures Mean sodium intake (g/day) as estimable by 24 h urine collections, without adjustment for non-urinary losses. Results In 2010, global mean sodium intake was 3.95 g/day (95% uncertainty interval: 3.89 to 4.01). This was nearly twice the WHO recommended limit of 2 g/day and equivalent to 10.06 (9.88–10.21) g/day of salt. Intake in men was ∼10% higher than in women; differences by age were small. Intakes were highest in East Asia, Central Asia and Eastern Europe (mean >4.2 g/day) and in Central Europe and Middle East/North Africa (3.9–4.2 g/day). Regional mean intakes in North America, Western Europe and Australia/New Zealand ranged from 3.4 to 3.8 g/day. Intakes were lower (<3.3 g/day), but more uncertain, in sub-Saharan Africa and Latin America. Between 1990 and 2010, modest, but uncertain, increases in sodium intakes were identified. Conclusions Sodium intakes exceed the recommended levels in almost all countries with small differences by age and sex. Virtually all populations would benefit from sodium reduction, supported by enhanced surveillance.

Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis.

The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood sources (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant sources (alpha-linolenic acid, ALA) and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95 % CI. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n = 13 studies; RR per 100 g/d = 1·12, 95 % CI = 0·94, 1·34); nor were consumption of EPA+DHA (n = 16 cohorts; RR per 250 mg/d = 1·04, 95 % CI = 0·97, 1·10) nor circulating levels of EPA+DHA biomarkers (n = 5 cohorts; RR per 3 % of total fatty acids = 0·94, 95 % CI = 0·75, 1·17). Both dietary ALA (n = 7 studies; RR per 0·5 g/d = 0·93, 95 % CI = 0·83, 1·04) and circulating ALA biomarker levels (n = 6 studies; RR per 0·1 % of total fatty acid = 0·90, 95 % CI = 0·80, 1·00, P = 0·06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I²~80 %) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity ( < 55 %) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-interaction ≤ 0·02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.

Global, regional, and national consumption levels of dietary fats and oils in 1990 and 2010: a systematic analysis including 266 country-specific nutrition surveys

Objectives To quantify global consumption of key dietary fats and oils by country, age, and sex in 1990 and 2010. Design Data were identified, obtained, and assessed among adults in 16 age- and sex-specific groups from dietary surveys worldwide on saturated, omega 6, seafood omega 3, plant omega 3, and trans fats, and dietary cholesterol. We included 266 surveys in adults (83% nationally representative) comprising 1 630 069 unique individuals, representing 113 of 187 countries and 82% of the global population. A multilevel hierarchical Bayesian model accounted for differences in national and regional levels of missing data, measurement incomparability, study representativeness, and sampling and modelling uncertainty. Setting and population Global adult population, by age, sex, country, and time. Results In 2010, global saturated fat consumption was 9.4%E (95%UI=9.2 to 9.5); country-specific intakes varied dramatically from 2.3 to 27.5%E; in 75 of 187 countries representing 61.8% of the world’s adult population, the mean intake was <10%E. Country-specific omega 6 consumption ranged from 1.2 to 12.5%E (global mean=5.9%E); corresponding range was 0.2 to 6.5%E (1.4%E) for trans fat; 97 to 440 mg/day (228 mg/day) for dietary cholesterol; 5 to 3,886 mg/day (163 mg/day) for seafood omega 3; and <100 to 5,542 mg/day (1,371 mg/day) for plant omega 3. Countries representing 52.4% of the global population had national mean intakes for omega 6 fat ≥5%E; corresponding proportions meeting optimal intakes were 0.6% for trans fat (≤0.5%E); 87.6% for dietary cholesterol (<300 mg/day); 18.9% for seafood omega 3 fat (≥250 mg/day); and 43.9% for plant omega 3 fat (≥1,100 mg/day). Trans fat intakes were generally higher at younger ages; and dietary cholesterol and seafood omega 3 fats generally higher at older ages. Intakes were similar by sex. Between 1990 and 2010, global saturated fat, dietary cholesterol, and trans fat intakes remained stable, while omega 6, seafood omega 3, and plant omega 3 fat intakes each increased. Conclusions These novel global data on dietary fats and oils identify dramatic diversity across nations and inform policies and priorities for improving global health.

Dietary quality among men and women in 187 countries in 1990 and 2010: a systematic assessment

Summary Background Healthy dietary patterns are a global priority to reduce non-communicable diseases. Yet neither worldwide patterns of diets nor their trends with time are well established. We aimed to characterise global changes (or trends) in dietary patterns nationally and regionally and to assess heterogeneity by age, sex, national income, and type of dietary pattern. Methods In this systematic assessment, we evaluated global consumption of key dietary items (foods and nutrients) by region, nation, age, and sex in 1990 and 2010. Consumption data were evaluated from 325 surveys (71·7% nationally representative) covering 88·7% of the global adult population. Two types of dietary pattern were assessed: one reflecting greater consumption of ten healthy dietary items and the other based on lesser consumption of seven unhealthy dietary items. The mean intakes of each dietary factor were divided into quintiles, and each quintile was assigned an ordinal score, with higher scores being equivalent to healthier diets (range 0–100). The dietary patterns were assessed by hierarchical linear regression including country, age, sex, national income, and time as exploratory variables. Findings From 1990 to 2010, diets based on healthy items improved globally (by 2·2 points, 95% uncertainty interval (UI) 0·9 to 3·5), whereas diets based on unhealthy items worsened (−2·5, −3·3 to −1·7). In 2010, the global mean scores were 44·0 (SD 10·5) for the healthy pattern and 52·1 (18·6) for the unhealthy pattern, with weak intercorrelation (r=–0·08) between countries. On average, better diets were seen in older adults compared with younger adults, and in women compared with men (p<0·0001 each). Compared with low-income nations, high-income nations had better diets based on healthy items (+2·5 points, 95% UI 0·3 to 4·1), but substantially poorer diets based on unhealthy items (−33·0, −37·8 to −28·3). Diets and their trends were very heterogeneous across the world regions. For example, both types of dietary patterns improved in high-income countries, but worsened in some low-income countries in Africa and Asia. Middle-income countries showed the largest improvement in dietary patterns based on healthy items, but the largest deterioration in dietary patterns based on unhealthy items. Interpretation Consumption of healthy items improved, while consumption of unhealthy items worsened across the world, with heterogeneity across regions and countries. These global data provide the best estimates to date of nutrition transitions across the world and inform policies and priorities for reducing the health and economic burdens of poor diet quality. Funding The Bill & Melinda Gates Foundation and Medical Research Council.

Trans fatty acids: effects on metabolic syndrome, heart disease and diabetes

The major dietary sources of trans fatty acids (TFAs) in most countries are partially hydrogenated vegetable oils. TFA consumption is a modifiable dietary risk factor for metabolic syndrome, diabetes mellitus, and coronary heart disease. Here, we review the available data on various effects of TFAs, including metabolic and signaling pathways that mediate these effects, affected tissues, and relationships with clinical end points. TFA consumption causes metabolic dysfunction: it adversely affects circulating lipid levels, triggers systemic inflammation, induces endothelial dysfunction, and, according to some studies, increases visceral adiposity, body weight, and insulin resistance. Dietary TFAs influence the function of multiple cell types, including hepatocytes, adipocytes, macrophages and endothelial cells. Among dietary fats and nutrients, TFAs seem to have a unique cardiometabolic imprint that is linked to insulin-resistance and metabolic-syndrome pathways. Consistent with these adverse physiological effects, consumption of even small amounts of TFAs (2% of total energy intake) is consistently associated with a markedly increased incidence of coronary heart disease. Relationships between TFA consumption and diabetes mellitus have been less consistent, possibly owing to differences in study designs. Nevertheless, the documented adverse effects of TFAs underscore their potential to cause harm and the importance of policy measures to minimize consumption of industrially produced TFAs.

Estimated Global, Regional, and National Disease Burdens Related to Sugar-Sweetened Beverage Consumption in 2010

Background— Sugar-sweetened beverages (SSBs) are consumed globally and contribute to adiposity. However, the worldwide impact of SSBs on burdens of adiposity-related cardiovascular diseases (CVDs), cancers, and diabetes mellitus has not been assessed by nation, age, and sex. Methods and Results— We modeled global, regional, and national burdens of disease associated with SSB consumption by age/sex in 2010. Data on SSB consumption levels were pooled from national dietary surveys worldwide. The effects of SSB intake on body mass index and diabetes mellitus, and of elevated body mass index on CVD, diabetes mellitus, and cancers were derived from large prospective cohort pooling studies. Disease-specific mortality/morbidity data were obtained from Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We computed cause-specific population-attributable fractions for SSB consumption, which were multiplied by cause-specific mortality/morbidity to compute estimates of SSB-attributable death/disability. Analyses were done by country/age/sex; uncertainties of all input data were propagated into final estimates. Worldwide, the model estimated 184 000 (95% uncertainty interval, 161 000–208 000) deaths/y attributable to SSB consumption: 133 000 (126 000–139 000) from diabetes mellitus, 45 000 (26 000–61 000) from CVD, and 6450 (4300–8600) from cancers. Five percent of SSB-related deaths occurred in low-income, 70.9% in middle-income, and 24.1% in high-income countries. Proportional mortality attributable to SSBs ranged from <1% in Japanese >65 years if age to 30% in Mexicans <45 years of age. Among the 20 most populous countries, Mexico had largest absolute (405 deaths/million adults) and proportional (12.1%) deaths from SSBs. A total of 8.5 (2.8, 19.2) million disability-adjusted life years were related to SSB intake (4.5% of diabetes mellitus–related disability-adjusted life years). Conclusions— SSBs are a single, modifiable component of diet that can impact preventable death/disability in adults in high-, middle-, and low-income countries, indicating an urgent need for strong global prevention programs.