Overweight, obesity and risk of cardiometabolic multimorbidity: pooled analysis of individual-level data for 120,813 adults from 16 cohort studies from the USA and Europe

Background Although overweight and obesity have been studied in relation to individual cardiometabolic diseases, their association with risk of cardiometabolic multimorbidity is poorly understood. Here we aimed to establish the risk of incident cardiometabolic multimorbidity (ie, at least two from: type 2 diabetes, coronary heart disease, and stroke) in adults who are overweight and obese compared with those who are a healthy weight. Methods We pooled individual-participant data for BMI and incident cardiometabolic multimorbidity from 16 prospective cohort studies from the USA and Europe. Participants included in the analyses were 35 years or older and had data available for BMI at baseline and for type 2 diabetes, coronary heart disease, and stroke at baseline and follow-up. We excluded participants with a diagnosis of diabetes, coronary heart disease, or stroke at or before study baseline. According to WHO recommendations, we classified BMI into categories of healthy (20·0–24·9 kg/m²), overweight (25·0–29·9 kg/m²), class I (mild) obesity (30·0–34·9 kg/m²), and class II and III (severe) obesity (≥35·0 kg/m²). We used an inclusive definition of underweight (<20 kg/m²) to achieve sufficient case numbers for analysis. The main outcome was cardiometabolic multimorbidity (ie, developing at least two from: type 2 diabetes, coronary heart disease, and stroke). Incident cardiometabolic multimorbidity was ascertained via resurvey or linkage to electronic medical records (including hospital admissions and death). We analysed data from each cohort separately using logistic regression and then pooled cohort-specific estimates using random-effects meta-analysis. Findings Participants were 120 813 adults (mean age 51·4 years, range 35–103; 71445 women) who did not have diabetes, coronary heart disease, or stroke at study baseline (1973–2012). During a mean follow-up of 10·7 years (1995–2014), we identified 1627 cases of multimorbidity. After adjustment for sociodemographic and lifestyle factors, compared with individuals with a healthy weight, the risk of developing cardiometabolic multimorbidity in overweight individuals was twice as high (odds ratio [OR] 2·0, 95% CI 1·7–2·4; p<0·0001), almost five times higher for individuals with class I obesity (4·5, 3·5–5·8; p<0·0001), and almost 15 times higher for individuals with classes II and III obesity combined (14·5, 10·1–21·0; p<0·0001). This association was noted in men and women, young and old, and white and non-white participants, and was not dependent on the method of exposure assessment or outcome ascertainment. In analyses of different combinations of cardiometabolic conditions, odds ratios associated with classes II and III obesity were 2·2 (95% CI 1·9–2·6) for vascular disease only (coronary heart disease or stroke), 12·0 (8·1–17·9) for vascular disease followed by diabetes, 18·6 (16·6–20·9) for diabetes only, and 29·8 (21·7–40·8) for diabetes followed by vascular disease. Interpretation The risk of cardiometabolic multimorbidity increases as BMI increases; from double in overweight people to more than ten times in severely obese people compared with individuals with a healthy BMI. Our findings highlight the need for clinicians to actively screen for diabetes in overweight and obese patients with vascular disease, and pay increased attention to prevention of vascular disease in obese individuals with diabetes

The InterLACE study: design, data harmonization and characteristics across 20 studies on women's health

The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE

Interpretation of the entire OECD/NEA-THAI HR test series including AREVA and AECL PARs using the code REKO-DIREKT

Additional file 1: Table S1. Effects (with 95% CI) of a doubling in the inflammatory marker at baseline on 5-year changes in heart rate and HRV indices (adjusting for waist cirumference)

Hazard ratios (95% CIs) for cause-specific mortality associated with consumption of tinned fruit, compared to the reference category of less than one serving of tinned fruit per month.

<p>Pooled results were calculated in random-effects meta-analysis of the log of the hazard ratios from individual cohorts, which were obtained in multivariable models including the same covariates as for analysis of all cause mortality (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0117796#pone.0117796.t002" target="_blank">Table 2</a>). Between-study heterogeneity measured by <i>I</i>² was, for cardiovascular mortality: 0% for one to three servings per month, 0% for one serving per week, and 0% for two or more servings per week; for cancer mortality 0% for one to three servings per month, 33.0% for one serving per week, and 0% for two or more servings per week; and for non-cardiovascular, non-cancer mortality: 21.2% for one to three servings per month, 0% for one serving per week, and 0% for two or more servings per week.</p

Hazard ratios (95% CIs) for all cause mortality by tinned fruit consumption.

<p>EPIC, European Prospective Investigation into Cancer and Nutrition.</p><p>^a All multivariable models adjusted for the following factors at baseline: sex, age (as underlying time variable), alcohol intake (four categories), physical activity level (four categories from low to high), prior diabetes (yes or no), smoking status (never, former or current in EPIC-Norfolk and Whitehall II; for EPIC-Oxford current smoking was divided into light or heavy smoker with the latter defined as ≥15 cigarettes smoked per day), body mass index (continuous for EPIC-Norfolk and Whitehall II and divided into five categories for EPIC-Oxford: <20.0, 20.0–22.4, 22.5–24.9, 25.0–27.4, and ≥27.5 kg/m²), socio-economic status (education level in four categories for EPIC-Norfolk and EPIC-Oxford, and employment grade in three categories for Whitehall II), energy intake (total energy intake for EPIC-Norfolk and EPIC-Oxford, and ratio of reported energy intake to estimated energy expenditure for Whitehall II). In addition, EPIC-Norfolk adjusted for antihypertensive drug use (yes or no), lipid lowering drug use (yes or no), family history of heart attack (yes or no), and family history of cancer (yes or no); EPIC-Oxford adjusted for long-term medical treatment (yes or no), parental history of heart attack or cancer (yes or no), and stratified hazard ratios by method of recruitment (general practice or post); and Whitehall II adjusted for antihypertensive drug use (yes or no), lipid lowering drug use (yes or no), ethnicity (white, south asian, black, other), and diet pattern (healthy, sweet, Mediterranean-like, unhealthy).</p><p>^b Pooled results were obtained in a random-effects meta-analysis of the log of the adjusted hazard ratios from individual cohorts.</p><p>^c Between-study heterogeneity measured by <i>I</i>² for the pooled multivariable adjusted hazard ratios were: 28.6% for one to three servings per month, 0% for one serving per week, 0% for two or more servings per week, and 0.2% for one serving per week increase.</p><p>Hazard ratios (95% CIs) for all cause mortality by tinned fruit consumption.</p

Hazard ratios (95% CIs) for all cause mortality associated with changing dietary intake from non-tinned fruits to tinned fruit.

<p>The effect on mortality of replacing 1 serving of tinned fruit with other types of fruit was estimated by introducing a variable for each fruit type assessed by the food frequency questionnaire (apples, pears, oranges, grapefruit, bananas, grapes, melons, peaches, strawberries, tinned fruit and dried fruit; each coded according to a participant´s intake in servings per week) and a total fruit variable (created as the sum of said fruit variables) into the multivariable model; an individual fruit variable (e.g. apples) was then removed, and in that model the hazard ratio for tinned fruit was interpreted as the effect of replacing 1 serving of the removed fruit variable (e.g. apples) with 1 serving of tinned fruit. Pooled results were obtained in a random-effects meta-analysis of the log of the multivariable adjusted hazard ratios from individual cohorts. Between-study heterogeneity measured by <i>I</i>² was: 0% for apples, 22.2% for pears, 0% for oranges, 14.7% for grapefruit, 29.6% for bananas, 20.7% for grapes, 0% for melons, 0% for peaches, 0% for strawberries, and 0% for dried fruit.</p

Associations Between Serum C-reactive Protein (CRP) Measured at Two Time Points and Carotid Intima-media Thickness (CIMT) Obtained from Standard Multivariable Regression Analysis.

<p>Only participants with no missing data in any of the covariates are included.</p>*<p>Adjusted for age, sex, systolic blood pressure, diastolic blood pressure, HDL-cholesterol, LDL-cholesterol, triglycerides, body mass index, smoking, physical inactivity, and low occupational status.</p

Participant Characteristics.

*<p>Low occupational status refers to clerical position in a three level hierarchy of administrative, professional and clerical employment grade.</p>†<p>Measured at mean age of 49.2 (SD = 6.0) years</p

Associations of C-reactive Protein (CRP) with Carotid Intima-media Thickness (CIMT) Obtained from the Instrumental Variables Analysis in Which <i>CRP</i> Haplotypes Act as An Instrument for the Non-confounded and Unbiased Effect of CRP.

<p>Associations of C-reactive Protein (CRP) with Carotid Intima-media Thickness (CIMT) Obtained from the Instrumental Variables Analysis in Which <i>CRP</i> Haplotypes Act as An Instrument for the Non-confounded and Unbiased Effect of CRP.</p

Contemporaneous Associations of Risk Factors with Serum C-reactive Protein (CRP) Concentration and Carotid Intima-media Thickness (CIMT) at Mean Age 61.0 Years^*.

*<p>Based on age- and sex-adjusted linear regression models.</p>†<p>Binary variables: 0 = never smoker, 1 = ever smoker; 0 = non-sedentary, 1 = sedentary; 0 = non-manual, 1 = manual.</p