Background: Knowledge of the number of deaths caused by risk factors is needed for health policy and priority setting. Our aim was to estimate the mortality effects of the following 12 modifiable dietary, lifestyle, and metabolic risk factors in the United States (US) using consistent and comparable methods: high blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure; overweight–obesity; high dietary trans fatty acids and salt; low dietary polyunsaturated fatty acids, omega-3 fatty acids (seafood), and fruits and vegetables; physical inactivity; alcohol use; and tobacco smoking. Methods and Findings: We used data on risk factor exposures in the US population from nationally representative health surveys and disease-specific mortality statistics from the National Center for Health Statistics. We obtained the etiological effects of risk factors on disease-specific mortality, by age, from systematic reviews and meta-analyses of epidemiological studies that had adjusted (i) for major potential confounders, and (ii) where possible for regression dilution bias. We estimated the number of disease-specific deaths attributable to all non-optimal levels of each risk factor exposure, by age and sex. In 2005, tobacco smoking and high blood pressure were responsible for an estimated 467,000 (95% confidence interval [CI] 436,000–500,000) and 395,000 (372,000–414,000) deaths, accounting for about one in five or six deaths in US adults. Overweight–obesity (216,000; 188,000–237,000) and physical inactivity (191,000; 164,000–222,000) were each responsible for nearly 1 in 10 deaths. High dietary salt (102,000; 97,000–107,000), low dietary omega-3 fatty acids (84,000; 72,000–96,000), and high dietary trans fatty acids (82,000; 63,000–97,000) were the dietary risks with the largest mortality effects. Although 26,000 (23,000–40,000) deaths from ischemic heart disease, ischemic stroke, and diabetes were averted by current alcohol use, they were outweighed by 90,000 (88,000–94,000) deaths from other cardiovascular diseases, cancers, liver cirrhosis, pancreatitis, alcohol use disorders, road traffic and other injuries, and violence. Conclusions: Smoking and high blood pressure, which both have effective interventions, are responsible for the largest number of deaths in the US. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of deaths in the US. Please see later in the article for the Editors’ Summary.

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The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors

Objective To design and develop a literature-derived, population-based dietary inflammatory index (DII) to compare diverse populations on the inflammatory potential of their diets. Design Peer-reviewed primary research articles published through December 2010 on the effect of diet on inflammation were screened for possible inclusion in the DII scoring algorithm. Qualifying articles were scored according to whether each dietary parameter increased (+1), decreased (−1) or had no (0) effect on six inflammatory biomarkers: IL-1β, IL-4, IL-6, IL-10, TNF-α and C-reactive protein. Setting The Dietary Inflammatory Index Development Study was conducted in the Cancer Prevention and Control Program of the University of South Carolina in Columbia, SC, USA from 2011 to 2012. Results A total of ≈6500 articles published through December 2010 on the effect of dietary parameters on the six inflammatory markers were screened for inclusion in the DII scoring algorithm. Eleven food consumption data sets from countries around the world were identified that allowed individuals’ intakes to be expressed relative to the range of intakes of the forty-five food parameters observed across these diverse populations. Qualifying articles (n 1943) were read and scored based on the forty-five pro- and anti-inflammatory food parameters identified in the search. When fit to this composite global database, the DII score of the maximally pro-inflammatory diet was +7·98, the maximally anti-inflammatory DII score was −8·87 and the median was +0·23. Conclusions The DII reflects both a robust literature base and standardization of individual intakes to global referent values. The success of this first-of-a-kind attempt at relating intakes of inflammation-modulating foods relative to global norms sets the stage for use of the DII in a wide variety of epidemiological and clinical studies.

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Designing and developing a literature-derived, population-based dietary inflammatory index

This study aims to estimate the absolute number of persons with hypertension (the hypertension burden) and time trends using data from the National Health and Nutrition Examination Survey of United States resident adults who had hypertension in 1999 to 2000. This information is vitally important for health policy, medical care, and public health strategy and resource allocation. At least 65 million adults had hypertension in 1999 to 2000. The total hypertension prevalence rate was 31.3%. This value represents adults with elevated systolic or diastolic blood pressure, or using antihypertensive medications (rate of 28.4%; standard error [SE], 1.1), and adults who otherwise by medical history were told at least twice by a physician or other health professional that they had high blood pressure (rate of 2.9%; SE, 0.4). The number of adults with hypertension increased by approximately 30% for 1999 to 2000 compared with at least 50 million for 1988 to 1994. The 50 million value was based on a rate of 23.4% for adults with elevated blood pressure or using antihypertensive medications and 5.5% for adults classified as hypertensive by medical history alone (28.9% total; P<0.001). The approximately 30% increase in the total number of adults with hypertension was almost 4-times greater than the 8.3% increase in total prevalence rate. These trends were associated with increased obesity and an aging and growing population. Approximately 35 million women and 30 million men had hypertension. At least 48 million non-Hispanic white adults, approximately 9 million non-Hispanic black adults, 3 million Mexican American, and 5 million other adults had hypertension in 1999 to 2000.

The Burden of Adult Hypertension in the United States 1999 to 2000: A Rising Tide

Atherosclerosis is a leading cause of vascular disease worldwide. Its major clinical manifestations include ischemic heart disease, ischemic stroke, and peripheral arterial disease. In high-income countries, there have been dramatic declines in the incidence and mortality from ischemic heart disease and ischemic stroke since the middle of the 20th century. For example, in the United Kingdom, the probability of death from vascular disease in middle-aged men (35-69 years) has decreased from 22% in 1950 to 6% in 2010. Most low- and middle-income countries have also reported declines in mortality from stroke over the last few decades, but mortality trends from ischemic heart disease have been more varied, with some countries reporting declines and others reporting increases (particularly those in Eastern Europe and Asia). Many major modifiable risk factors for atherosclerosis have been identified, and the causal relevance of several risk factors is now well established (including, but not limited to, smoking, adiposity, blood pressure, blood cholesterol, and diabetes mellitus). Widespread changes in health behaviors and use of treatments for these risk factors are responsible for some of the dramatic declines in vascular mortality in high-income countries. In order that these declines continue and are mirrored in less wealthy nations, increased efforts are needed to tackle these major risk factors, particularly smoking and the emerging obesity epidemic.

Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease

This review in the Global Health series focuses on the role of smoking, alcohol, and obesity in the burden of noncommunicable disease.

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Behavioral and dietary risk factors for noncommunicable diseases.

Recent studies show that antioxidants may reduce the risk of osteoporosis. This study showed the associations of bone mineral density with dietary patterns of antioxidant vitamins and carotenoids. The findings suggest the combination of vitamin C and β-cryptoxanthin intakes might provide benefit to bone health in post-menopausal Japanese female subjects. Recent epidemiological studies show antioxidants may reduce the risk of osteoporosis, but little is known about the dietary patterns of antioxidant vitamin and carotenoid intakes and their relation with bone mineral density (BMD). A total of 293 post-menopausal female subjects who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Radial BMD was measured using dual-energy X-ray absorptiometry. Dietary intakes of antioxidant vitamins and carotenoids were assessed by using a validated food-frequency questionnaire. Dietary patterns were identified on a selected set of antioxidants through principal component factor analysis. Three dietary patterns were identified. The “retinol” pattern, characterized by notably high intakes of preformed retinol, zeaxanthin, and vitamin E, was positively associated with the risk for low BMD. In contrast, the “β-cryptoxanthin” pattern, characterized by notably high intakes of β-cryptoxanthin and vitamin C, was negatively associated with low BMD. The odds ratios for low BMD in the highest tertiles of dietary intakes of preformed retinol, vitamin C, and β-cryptoxanthin against the lowest tertiles were 3.22 [95% confidence interval (CI), 1.38–7.51], 0.25 (CI, 0.10–0.66), and 0.40 (CI, 0.17–0.92), respectively, after adjustments for confounders. However, negative associations of vitamin C and β-cryptoxanthin with low BMD were not significant after further adjustment for intake of β-cryptoxanthin or vitamin C, respectively. Higher intakes of both vitamin C and β-cryptoxanthin were significantly associated with low BMD (P < 0.05). The combination of vitamin C and β-cryptoxanthin may be associated with radial BMD in post-menopausal Japanese female subjects.

Dietary patterns of antioxidant vitamin and carotenoid intake associated with bone mineral density: findings from post-menopausal Japanese female subjects

High intake of fruit and vegetables may reduce the risk of osteoporosis. Carotenoids exist in abundance in these foods. This study showed the association of bone mineral density with serum carotenoids. The findings suggest that β-cryptoxanthin and β-carotene might provide benefits to bone health in post-menopausal female subjects. Antioxidant carotenoids are abundant in fruit and vegetables. Recent epidemiological studies show that high intakes of fruit and vegetables may reduce the risk of osteoporosis, but little is known about the association of bone mineral density (BMD) with serum carotenoids. A total of 699 subjects (222 males and 477 females) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Radial BMD was measured using dual-energy X-ray absorptiometry (DXA). The associations of serum carotenoid concentrations with the radial BMD were evaluated cross-sectionally. In male and pre-menopausal female subjects, the six serum carotenoids were not associated with the radial BMD. On the other hand, in post-menopausal female subjects, serum β-cryptoxanthin and β-carotene were weakly but positively correlated with the radial BMD. After adjustment for confounders, the odds ratio (OR) for the lowest quartile of BMD in the high groups (Q2–Q4) of serum β-cryptoxanthin against the lowest quartile (Q1) was 0.45 (95% confidence interval: 0.22–0.95) in post-menopausal female subjects. However, this association was not significant after further adjusting for intakes of minerals and vitamins. Antioxidant carotenoids, especially β-cryptoxanthin, significantly but partly associate with the radial BMD in post-menopausal female subjects.

Bone mineral density in post-menopausal female subjects is associated with serum antioxidant carotenoids

Few prospective data from the Asia Pacific region are available relating body mass index to the risk of diabetes. Our objective was to provide reliable age, sex and region specific estimates of the associations between body mass index and diabetes. Twenty-seven cohort studies from Asia, New Zealand and Australia, including 154,989 participants, contributed 1,244,793 person-years of follow-up. Outcome data included a combination of incidence of diabetes (based on blood glucose measurements) and fatal diabetes events. Hazard ratios were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk and smoking. During follow-up (mean = 8 years), 75 fatal diabetes events and 242 new cases of diabetes were documented. There were continuous positive associations between baseline body mass index and risk of diabetes with each 2 kg/m(2) lower body mass index associated with a 27% (23-30%) lower risk of diabetes. The associations were stronger in younger age groups, and regional comparisons demonstrated slightly stronger associations in Asian than in Australasian cohorts (P = 0.04). This overview provides evidence of a strong continuous association between body mass index and diabetes in the Asia Pacific region. The results indicate considerable potential for reduction in incidence of diabetes with population-wide lowering of body mass index in this region.

Body mass index and risk of diabetes mellitus in the Asia-Pacific region.

Introduction
Recent epidemiological studies show that high intakes of carotenoids might be useful to maintain bone health, but little is known about the association of serum carotenoids with change of bone mineral density (BMD). The objective of this study was to investigate longitudinally whether serum carotenoids are associated with bone loss.

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Mieko Nakamura

Papers

Dietary patterns of antioxidant vitamin and carotenoid intake associated with bone mineral density: findings from post-menopausal Japanese female subjects

Bone mineral density in post-menopausal female subjects is associated with serum antioxidant carotenoids

Body mass index and risk of diabetes mellitus in the Asia-Pacific region.

High Serum Carotenoids Associated with Lower Risk for Bone Loss and Osteoporosis in Post-Menopausal Japanese Female Subjects: Prospective Cohort Study

The homeostasis model assessment-insulin resistance index is inversely associated with serum carotenoids in non-diabetic subjects.