Kaveh Hajifathalian

Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: A pooled analysis of 97 prospective cohorts with 1.8 million participants

Summary Background Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. Methods We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57 161 coronary heart disease and 31 093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m2, or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators. Findings The HR for each 5 kg/m2 higher BMI was 1·27 (95% CI 1·23–1·31) for coronary heart disease and 1·18 (1·14–1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12–1·18) for coronary heart disease and 1·04 (1·01–1·08) for stroke, suggesting that 46% (95% CI 42–50) of the excess risk of BMI for coronary heart disease and 76% (65–91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28–35) of the excess risk for coronary heart disease and 65% (56–75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to <30 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), with 50% (44–58) of the excess risk of overweight and 44% (41–48) of the excess risk of obesity for coronary heart disease mediated by the selected three mediators. The percentages for stroke were 98% (69–155) for overweight and 69% (64–77) for obesity. Interpretation Interventions that reduce high blood pressure, cholesterol, and glucose might address about half of excess risk of coronary heart disease and three-quarters of excess risk of stroke associated with high BMI. Maintenance of optimum bodyweight is needed for the full benefits. Funding US National Institute of Health, UK Medical Research Council, National Institute for Health Research Comprehensive Biomedical Research Centre at Imperial College Healthcare NHS Trust, Lown Scholars in Residence Program on cardiovascular disease prevention, and Harvard Global Health Institute Doctoral Research Grant.

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. DOI: http://dx.doi.org/10.7554/eLife.13410.001

A novel risk score to predict cardiovascular disease risk in national populations (Globorisk): a pooled analysis of prospective cohorts and health examination surveys

BACKGROUND Treatment of cardiovascular risk factors based on disease risk depends on valid risk prediction equations. We aimed to develop, and apply in example countries, a risk prediction equation for cardiovascular disease (consisting here of coronary heart disease and stroke) that can be recalibrated and updated for application in different countries with routinely available information. METHODS We used data from eight prospective cohort studies to estimate coefficients of the risk equation with proportional hazard regressions. The risk prediction equation included smoking, blood pressure, diabetes, and total cholesterol, and allowed the effects of sex and age on cardiovascular disease to vary between cohorts or countries. We developed risk equations for fatal cardiovascular disease and for fatal plus non-fatal cardiovascular disease. We validated the risk equations internally and also using data from three cohorts that were not used to create the equations. We then used the risk prediction equation and data from recent (2006 or later) national health surveys to estimate the proportion of the population at different levels of cardiovascular disease risk in 11 countries from different world regions (China, Czech Republic, Denmark, England, Iran, Japan, Malawi, Mexico, South Korea, Spain, and USA). FINDINGS The risk score discriminated well in internal and external validations, with C statistics generally 70% or more. At any age and risk factor level, the estimated 10 year fatal cardiovascular disease risk varied substantially between countries. The prevalence of people at high risk of fatal cardiovascular disease was lowest in South Korea, Spain, and Denmark, where only 5-10% of men and women had more than a 10% risk, and 62-77% of men and 79-82% of women had less than a 3% risk. Conversely, the proportion of people at high risk of fatal cardiovascular disease was largest in China and Mexico. In China, 33% of men and 28% of women had a 10-year risk of fatal cardiovascular disease of 10% or more, whereas in Mexico, the prevalence of this high risk was 16% for men and 11% for women. The prevalence of less than a 3% risk was 37% for men and 42% for women in China, and 55% for men and 69% for women in Mexico. INTERPRETATION We developed a cardiovascular disease risk equation that can be recalibrated for application in different countries with routinely available information. The estimated percentage of people at high risk of fatal cardiovascular disease was higher in low-income and middle-income countries than in high-income countries. FUNDING US National Institutes of Health, UK Medical Research Council, Wellcome Trust.

Mediators of the effect of body mass index on coronary heart disease: decomposing direct and indirect effects.

Background: The prevalence of overweight and obesity is rising globally and together they constitute a major risk factor for coronary heart disease (CHD). Previous estimates of direct effects of high body mass index (BMI) on CHD did not consider an interaction between BMI and its mediators and did not include inflammatory biomarkers as potential mediators. Methods: We analyzed data from 9 prospective cohort studies with 58,322 participants and 9,459 CHD events and decomposed the total effects into natural direct and indirect effects using a 2-stage regression model. We examined overweight (BMI = 25 to <30 kg/m2) separately. We pooled hazard ratios using random-effects models and calculated the percentages of excess relative risk mediated by blood pressure, cholesterol, glucose, fibrinogen and high-sensitive C-reactive protein. Results: There was no interaction between BMI and its mediators in the multiplicative scale (P < 0.05 for all). Blood pressure was the most important mediator. The percentage of excess relative risk of overweight (versus normal BMI, 20 to <25 kg/m2) mediated was 28% for blood pressure, 10% for blood glucose, and 14% for cholesterol. The same percentages for obesity were 37% for blood pressure, 17% for blood glucose, and 6% for cholesterol. The percentage mediated through all three metabolic risk factors together was 47% (95% confidence interval = 33%–63%) for overweight and 52% (38%–68%) for obesity. Fibrinogen mediated 6% to 9% and high-sensitive C-reactive protein mediated 6% to 8% of the excess relative risk for overweight and obese participants. Conclusions: Metabolic mediators explain about half of the adverse effects of high BMI on CHD. The role of inflammatory and prothrombotic biomarkers is much smaller than that of metabolic factors.

Do mass media campaigns improve physical activity? a systematic review and meta-analysis

BackgroundMass media campaigns are frequently used to influence the health behaviors of various populations. There are currently no quantitative meta-analyses of the effect of mass media campaigns on physical activity in adults.MethodsWe searched six electronic databases from their inception to August 2012 and selected prospective studies that evaluated the effect of mass media campaigns on physical activity in adults. We excluded studies that did not have a proper control group or did not report the uncertainties of the effect estimates. Two reviewers independently screened the title/abstracts and full articles. We used random-effects models to pool effect estimates across studies for 3 selected outcomes.ResultsNine prospective cohorts and before-after studies that followed-up 27,601 people over 8 weeks to 3 years met the inclusion criteria. Based on the pooled results from these studies, mass media campaigns had a significant effect on promoting moderate intensity walking (pooled relative risk (RR) from 3 studies=1.53, 95% Confidence Interval: 1.25 to 1.87), but did not help participants achieve sufficient levels of physical activity [4 studies pooled RR=1.02, 95% CI: 0.91 to 1.14)]. The apparent effect of media campaigns on reducing sedentary behavior (pooled RR=1.15, 95% CI: 1.03 to 1.30) was lost when a relatively low-quality study with large effects was excluded in a sensitivity analysis. In subgroup analyses, campaigns that promoted physical activity as a ‘social norm’ seemed to be more effective in reducing sedentary behavior.ConclusionMass media campaigns may promote walking but may not reduce sedentary behavior or lead to achieving recommended levels of overall physical activity. Further research is warranted on different campaign types and in low- and middle- income countries.

Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: a pooled analysis of prospective cohorts and health surveys.

BACKGROUND Worldwide implementation of risk-based cardiovascular disease (CVD) prevention requires risk prediction tools that are contemporarily recalibrated for the target country and can be used where laboratory measurements are unavailable. We present two cardiovascular risk scores, with and without laboratory-based measurements, and the corresponding risk charts for 182 countries to predict 10-year risk of fatal and non-fatal CVD in adults aged 40-74 years. METHODS Based on our previous laboratory-based prediction model (Globorisk), we used data from eight prospective studies to estimate coefficients of the risk equations using proportional hazard regressions. The laboratory-based risk score included age, sex, smoking, blood pressure, diabetes, and total cholesterol; in the non-laboratory (office-based) risk score, we replaced diabetes and total cholesterol with BMI. We recalibrated risk scores for each sex and age group in each country using country-specific mean risk factor levels and CVD rates. We used recalibrated risk scores and data from national surveys (using data from adults aged 40-64 years) to estimate the proportion of the population at different levels of CVD risk for ten countries from different world regions as examples of the information the risk scores provide; we applied a risk threshold for high risk of at least 10% for high-income countries (HICs) and at least 20% for low-income and middle-income countries (LMICs) on the basis of national and international guidelines for CVD prevention. We estimated the proportion of men and women who were similarly categorised as high risk or low risk by the two risk scores. FINDINGS Predicted risks for the same risk factor profile were generally lower in HICs than in LMICs, with the highest risks in countries in central and southeast Asia and eastern Europe, including China and Russia. In HICs, the proportion of people aged 40-64 years at high risk of CVD ranged from 1% for South Korean women to 42% for Czech men (using a ≥10% risk threshold), and in low-income countries ranged from 2% in Uganda (men and women) to 13% in Iranian men (using a ≥20% risk threshold). More than 80% of adults were similarly classified as low or high risk by the laboratory-based and office-based risk scores. However, the office-based model substantially underestimated the risk among patients with diabetes. INTERPRETATION Our risk charts provide risk assessment tools that are recalibrated for each country and make the estimation of CVD risk possible without using laboratory-based measurements. FUNDING National Institutes of Health.

Co-testing for detection of high-grade cervical intraepithelial neoplasia and cancer compared with cytology alone: a meta-analysis of randomized controlled trials

BACKGROUND Human papillomavirus (HPV) DNA testing combined with cytology has been recommended as a primary cervical cancer screening strategy. METHODS PubMed/MEDLINE, Embase, the Cochrane Library and the NIH trial registry were searched for randomized controlled trials comparing co-testing with cytology alone for the detection of high-grade CIN lesions and cancers. Of 1156 articles identified, four met inclusion criteria. The performance of co-testing and cytology alone was compared at baseline screening, second round screening and overall. Cumulative meta-analysis, Beggs test, Eggers test and sensitivity analysis were performed. RESULTS At baseline, co-testing was associated with a significantly higher detection rate of CIN 2+ [risk ratio (RR) = 1.41, 95% confidence interval (CI): 1.12, 1.76] and a non-significantly higher CIN 3+ detection rate (RR = 1.15, 95% CI: 0.99, 1.33). At second round screening, co-testing was associated with significantly lower detection rates of both CIN 2+ and CIN 3+ (RR = 0.77, 95% CI: 0.63, 0.93; RR = 0·68, 95% CI: 0.55, 0.85). The overall detection rate did not differ between co-testing and cytology alone for CIN 2+ (RR: 1·19, 95% CI: 0.99, 1.46) or CIN3+ (RR: 0.99, 95% CI: 0.87, 1.14). CONCLUSION Co-testing increases the detection of CIN2+ lesions at baseline and significantly decreases the detection rates of CIN2+ or CIN3+ lesions at subsequent screening compared with cytology alone.

Sick Populations and Sick Subpopulations: Reducing Disparities in Cardiovascular Disease Between Blacks and Whites in the United States

Background: Cardiovascular disease (CVD) death rates are much higher in blacks than whites in the United States. It is unclear how CVD risk and events are distributed among blacks versus whites and how interventions reduce racial disparities. Methods: We developed risk models for fatal and for fatal and nonfatal CVD using 8 cohorts in the United States. We used 6154 adults who were 50 to 69 years of age in the National Health and Nutrition Examination Survey 1999 to 2012 to estimate the distributions of risk and events in blacks and whites. We estimated the total and disparity impacts of a range of population-wide, targeted, and risk-based interventions on 10-year CVD risks and event rates. Results: Twenty-five percent (95% confidence interval [CI], 22–28) of black men and 12% (95% CI, 10–14) of black women were at ≥6.67% risk of fatal CVD (almost equivalent to 20% risk of fatal or nonfatal CVD) compared with 10% (95% CI, 8–12) of white men and 3% (95% CI, 2–4) of white women. These high-risk individuals accounted for 55% (95% CI, 49–59) of CVD deaths among black men and 42% (95% CI, 35–46) in black women compared with 30% (95% CI, 24–35) in white men and 18% (95% CI, 13–22) in white women. We estimated that an intervention that treated multiple risk factors in high-risk individuals could reduce black-white difference in CVD death rate from 1659 to 1244 per 100 000 in men and from 1320 to 897 in women. Rates of fatal and nonfatal CVD were generally similar between black and white men. In women, a larger proportion of women were at ≥7.5% risk of CVD (30% versus 19% in whites), and an intervention that targeted multiple risk factors among this group was estimated to reduce black-white differences in CVD rates from 1688 to 1197 per 100 000. Conclusions: A substantially larger proportion of blacks have a high risk of fatal CVD and bear a large share of CVD deaths. A risk-based intervention that reduces multiple risk factors could substantially reduce overall CVD rates and racial disparities in CVD death rates.

Challenges of monitoring global diabetes prevalence

Peter Bennett and colleagues state in their letter that it is unclear whether analyses of diabetes trends by the NCD Risk Factor Collaboration (NCD-RisC) accounted for whether glucose was measured in whole blood versus plasma. NCD-RisC’s approach to handling data sources that had measured glucose in whole blood instead of plasma are described in our global trends papers—in the methods section of the Article by Danaei and colleagues and in table 2 of the appendix of the 2016 Article by NCD-RisC. Specifically, following recommendations by Sacks and colleagues in 2011, measurements of fasting and postprandial gluc ose in venous whole blood and of fasting glucose in capillary whole blood were multiplied by 1·11 to convert them to equivalent plasma glucose concentrations before diabetes prevalence was calculated; a few studies in which postprandial glucose was measured in capillary whole blood were excluded because the association with venous plasma glucose is highly variable. This protocol was applied to individual-level glucose data, including to those from WHO STEPS surveys.

Lack of Incremental Effect of Histamine Receptor Antagonists over Proton Pump Inhibitors on the Risk of Neoplastic Progression in Patients with Barrett's Esophagus: A Cohort Study.

Long‐term acid suppression reduces the risk of progression to esophageal adenocarcinoma (EAC) in patients with Barretts esophagus (BE). Given recent reports about the harmful effects of using chronic proton pump inhibitors (PPI) there is renewed interest in alternative methods of acid suppression. Hence, we studied the effect of H2 receptor antagonists (H2RA) on the risk of progression to neoplasia in our BE cohort.