Person:

Wang, Dong

Objective: To examine whether exposure to the Chinese famine during fetal life and early childhood is associated with the risks of metabolic syndrome and whether this association is modified by later life environment. Research Design and Methods: We used data of 7,874 adults born between 1954 and 1964 from the 2002 China National Nutrition and Health Survey. Famine exposure groups were defined as nonexposed; fetal exposed; and early childhood, midchildhood, or late childhood exposed. Excess death rate was used to determine the severity of the famine. The ATP III criteria were used for the definition of metabolic syndrome (three or more of the following variables: elevated fasting triglyceride levels, lower HDL cholesterol levels, elevated fasting glucose levels, higher waist circumference, high blood pressure). Results: In severely affected famine areas, adults who were exposed to the famine during fetal life had a higher risk of metabolic syndrome, as compared with nonexposed subjects (odds ratio 3.13 [95% CI 1.24–7.89, P = 0.016]). Similar associations were observed among adults who were exposed to the famine during early childhood, but not for adults exposed to the famine during mid- or late childhood. Participants who were born in severely affected famine areas and had Western dietary habits in adulthood or were overweight in adulthood had a particularly high risk of metabolic syndrome in later life. Conclusions: Exposure to the Chinese famine during fetal life or infancy is associated with an increased risk of metabolic syndrome in adulthood. These associations are stronger among subjects with a Western dietary pattern or who were overweight in adulthood.

The purpose of this cross-sectional study was to investigate the joint associations of physical activity level (PAL) and dietary patterns in relation to cardiovascular disease (CVD) risk factors among Chinese men. The study population consisted of 13 511 Chinese males aged 18–59 years from the 2002 China National Nutrition and Health Survey. Based on dietary data collected by a food frequency questionnaire, four dietary patterns were identified and labeled as “Green Water” (high consumption of rice, vegetables, seafood, pork, and poultry), “Yellow Earth” (high consumption of wheat flour products and starchy tubers), “New Affluent” (high consumption of animal sourced foods and soybean products), and “Western Adopter” (high consumption of animal sourced foods, cakes, and soft drinks). From the information collected by a 1-year physical activity questionnaire, PAL was calculated and classified into 4 categories: sedentary, low active, active, and very active. As compared with their counterparts from the New Affluent pattern, participants who followed the Green Water pattern had a lower likelihood of abdominal obesity (AO; 50.2%), hypertension (HT; 37.9%), hyperglycemia (HG; 41.5%), elevated triglyceride (ETG; 14.5%), low HDL (LHDL; 39.8%), and metabolic syndrome (MS; 51.9%). When compared to sedentary participants, the odds ratio of participants with very active PAL was 0.62 for AO, 0.85 for HT, 0.71 for HG, 0.76 for ETG, 0.74 for LHDL, and 0.58 for MS. Individuals who followed both very active PAL and the Green Water pattern had a lower likelihood of CVD risk factors (AO: 65.8%, HT: 39.1%, HG: 57.4%, ETG: 35.4%, LHDL: 56.1%, and MS: 75.0%), compared to their counterparts who followed both sedentary PAL and the New Affluent pattern. In addition, adherence to both healthy dietary pattern and very active PAL presented a remarkable potential for CVD risk factor prevention.

In Chapters 1 and 2, we examined two key components of heathy dietary patterns, specific types of dietary fat and consumption of fruit and vegetables, in relation to total and cause-specific mortality in two prospective cohort studies, the Nurses’ Health Study and the Health Professionals Follow-up Study. Dietary intake was assessed using semi-quantitative food frequency questionnaires at baseline and updated every 2 to 4 years. In Chapter 1, we found that higher saturated and trans fat intakes were associated with higher mortality, whereas polyunsaturated and monounsaturated fat intakes were inversely associated with mortality. Replacing 5% of energy from saturated fats with equivalent energy from polyunsaturated fats and monounsaturated fats was associated with 27% and 13% estimated reductions in total mortality, respectively. Intake of n-6 polyunsaturated fat, especially linoleic acid, was inversely associated with mortality, while marine n-3 polyunsaturated fat intake was associated with a modestly lower total mortality. In Chapter 2, we observed an inverse and nonlinear association between fruit and vegetable consumption and mortality. Consumption of five servings of fruit and vegetables daily, two servings for total fruit and three servings for total vegetables, were associated with the lowest total mortality, but above that level, higher consumptions were not associated with additional risk reductions. Higher consumptions of most fruit and vegetable subgroups were associated with lower risks of total mortality, whereas higher intakes of starchy vegetables such as peas and corn were associated with slightly higher risk of total mortality. In Chapter 3, we investigated the interrelationships between plasma ceramide concentrations, Mediterranean dietary pattern and cardiovascular disease (CVD) in the PREDIMED trial, a randomized controlled trial on the Mediterranean diet for primary prevention of CVD, using a case-cohort design. We observed strong positive associations between plasma ceramide concentrations and CVD risk. The association between ceramide concentration and incident CVD significantly varied by intervention groups. A Mediterranean diet may mitigate the deleterious effects of elevated plasma ceramide concentration. In summary, our findings from the three studies support current dietary recommendations to replace saturated and trans fat with unsaturated fats, increase fruit and vegetable consumption and adopt healthy Mediterranean-style dietary patterns.

Background: The relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions. Methods and Results: We designed a case‐cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography–tandem mass spectrometry to measure, at baseline and at 1 year of follow‐up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N‐oxide, betaine, choline, phosphocholine, and α‐glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1‐SD increase in choline and α‐glycerophosphocholine metabolites were 1.24 (1.05–1.46) and 1.24 (1.03–1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21‐fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36–3.59; P<0.001 for trend) and a 2.27‐fold higher risk of stroke (95% confidence interval, 1.24–4.16; P<0.001 for trend). Participants in the higher quartiles of the score who were randomly assigned to the control group had a higher risk of CVD compared with participants in the lower quartile and assigned to the Mediterranean diet groups (P=0.05 for interaction). No significant associations were observed for 1‐year changes in individual plasma metabolites and CVD. Conclusions: A metabolite score combining plasma metabolites from the choline pathway was associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk. Clinical Trial Registration URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.

Few studies have formally tested the interaction between diet and the gut microbiome in the context of cardiometabolic health, particularly with the microbiome considered as a potential mediator rather than a target of dietary effects. Here, we investigated 307 male participants in the Health Professionals Follow-Up Study who provided up to four stool samples each, yielding 925 shotgun metagenomes and 340 metatranscriptomes, long-term dietary information, and biomarkers of glucose homeostasis, lipid metabolism, and inflammation from blood samples. We demonstrate that a healthy Mediterranean-style dietary pattern is associated with functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary, depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings represent a step forward in the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome.