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Proteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All-Cause Mortality: The Framingham Heart Study.

ABSTRACT: Background Biological mechanisms underlying the association of a healthy diet with chronic diseases remain unclear. Targeted proteomics may facilitate the understanding of mechanisms linking diet to chronic diseases. Methods and Results We examined 6360 participants (mean age 50 years; 54% women) in the Framingham Heart Study. The associations between diet and 71 cardiovascular disease (CVD)-related proteins were examined using 3 diet quality scores: the Alternate Healthy Eating Index, the modified Mediterranean-style Diet Score, and the modified Dietary Approaches to Stop Hypertension diet score. A mediation analysis was conducted to examine which proteins mediated the associations of diet with incident CVD and all-cause mortality. Thirty of the 71 proteins were associated with at least 1 diet quality score (P<0.0007) after adjustment for multiple covariates in all study participants and confirmed by an internal validation analysis. Gene ontology analysis identified inflammation-related pathways such as regulation of cell killing and neuroinflammatory response (Bonferroni corrected P<0.05). During a median follow-up of 13 years, we documented 512 deaths and 488 incident CVD events. Higher diet quality scores were associated with lower risk of CVD (P≤0.03) and mortality (P≤0.004). After adjusting for multiple potential confounders, 4 proteins (B2M [beta-2-microglobulin], GDF15 [growth differentiation factor 15], sICAM1 [soluble intercellular adhesion molecule 1], and UCMGP [uncarboxylated matrix Gla-protein]) mediated the association between at least 1 diet quality score and all-cause mortality (median proportion of mediation ranged from 8.6% to 25.9%). We also observed that GDF15 mediated the association of the Alternate Healthy Eating Index with CVD (median proportion of mediation: 8.6%). Conclusions Diet quality is associated with new-onset CVD and mortality and with circulating CVD-related proteins. Several proteins appear to mediate the association of diet with these outcomes.

SUBMITTER: Kim Y

PROVIDER: S-EPMC8649513 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Arterial arteriosclerosis and atherosclerosis reflect vascular disease, the subclinical detection of which allows opportunity for cardiovascular disease (CVD) prevention. Larger cohort studies simultaneously quantifying anatomic thoracic and abdominal aortic pathologic abnormalities are lacking in the literature. Purpose To investigate the association of aortic wall area (AWA) and atherosclerotic plaque presence and burden as measured on MRI scans with incident CVD in a community sample. Materials and Methods In this prospective cohort study, participants in the Framingham Heart Study Offspring Cohort without prevalent CVD underwent 1.5-T MRI (between 2002-2005) of the descending thoracic and abdominal aorta with electrocardiogram-gated axial T2-weighted black-blood acquisitions. The wall thickness of the thoracic aorta was measured at the pulmonary bifurcation level and used to calculate the AWA as the difference between cross-sectional vessel area and lumen area. For primary or secondary analyses, multivariable Cox proportional hazards regression models were used to examine the association of aortic MRI measures with risk of first-incident CVD events or stroke and coronary heart disease, respectively. Results In 1513 study participants (mean age, 64 years ± 9 [SD]; 842 women [56%]), 223 CVD events occurred during follow-up (median, 13.1 years), of which 97 were major events (myocardial infarction, ischemic stroke, or CVD death). In multivariable analysis, thoracic AWA and prevalent thoracic plaque were associated with incident CVD (hazard ratio [HR], 1.20 per SD unit [95% CI: 1.05, 1.37] [P = .006] and HR, 1.63 [95% CI: 1.12, 2.35] [P = .01], respectively). AWA and prevalent thoracic plaque were associated with increased hazards: 1.32 (95% CI: 1.07, 1.62; P = .01) and 2.20 (95% CI: 1.28, 3.79; P = .005), for stroke and coronary heart disease, respectively. Conclusion In middle-aged community-dwelling adults, thoracic aortic wall area (AWA), plaque prevalence, and plaque volumes measured with MRI were independently associated with incident cardiovascular disease, with AWA associated in particular with stroke, and plaque associated with coronary heart disease. Clinical trial registration no. NCT00041418 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Peshock in this issue.

Project description:Some variables including age, comorbidity of diabetes, and so on at dialysis initiation are associated with patient prognosis. Cardiovascular (CV) events are a major cause of death, and adequate models that predict prognosis in dialysis patients are warranted. Therefore, we created models using some variables at dialysis initiation. We used a database of 1,520 consecutive dialysis patients (median age, 70 years; 492 women [32.4%]) from a multicenter prospective cohort study. We established the primary endpoint as a composite of the incidence of first CV events or all-cause death. A multivariable Cox proportional hazard regression model was used to construct a model. We considered a complex and a simple model. We used area under the receiver operating characteristic curve (AUROC) to assess and compare the predictive performances of the prediction models and evaluated the improvement in discrimination using the complex model versus the simple model using net reclassification improvement (NRI). We then assessed integrated discrimination improvement (IDI) to evaluate improvements in average sensitivity and specificity. Of 392 deaths, 152 were CV-related. Totally, 506 CV events occurred during the follow-up period (median 1,285 days). Finally, 692 patients reached the primary endpoint. Baseline data were set at dialysis initiation. AUROC for the primary endpoint was 0.737 (95% confidence interval [CI], 0.712-0.761) in the simple model and 0.765 (95% CI, 0.741-0.788) in the complex model. There were significant intergroup differences in NRI (0.44; 95% CI, 0.34-0.53; p < 0.001) and IDI (0.02; 95% CI, 0.02-0.03; p < 0.001). We prepared a Shiny R application for each model to automatically calculate the predicted occurrence probability (https://statacademy.shinyapps.io/App_inaguma_20190717/). The complex model made more accurate predictions than the simple model. However, the intergroup difference was not significant. Hence, the simple model was more useful than the complex model. The tool was useful in a real-world clinical setting because it required only routinely available variables. Moreover, we emphasized that the tool could predict the incidence of CV events or all-cause mortality for individual patients. In the future, we must confirm its external validity in other prospective cohorts.

Project description:Increased attention in dietary research and guidance has been focused on dietary patterns, rather than on single nutrients or food groups, because dietary components are consumed in combination and correlated with one another. However, the collective body of research on the topic has been hampered by the lack of consistency in methods used. We examined the relationships between 4 indices--the Healthy Eating Index-2010 (HEI-2010), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)--and all-cause, cardiovascular disease (CVD), and cancer mortality in the NIH-AARP Diet and Health Study (n = 492,823). Data from a 124-item food-frequency questionnaire were used to calculate scores; adjusted HRs and 95% CIs were estimated. We documented 86,419 deaths, including 23,502 CVD- and 29,415 cancer-specific deaths, during 15 y of follow-up. Higher index scores were associated with a 12-28% decreased risk of all-cause, CVD, and cancer mortality. Specifically, comparing the highest with the lowest quintile scores, adjusted HRs for all-cause mortality for men were as follows: HEI-2010 HR: 0.78 (95% CI: 0.76, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.78), aMED HR: 0.77 (95% CI: 0.75, 0.79), and DASH HR: 0.83 (95% CI: 0.80, 0.85); for women, these were HEI-2010 HR: 0.77 (95% CI: 0.74, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.79), aMED HR: 0.76 (95% CI: 0.73, 0.79), and DASH HR: 0.78 (95% CI: 0.75, 0.81). Similarly, high adherence on each index was protective for CVD and cancer mortality examined separately. These findings indicate that multiple scores reflect core tenets of a healthy diet that may lower the risk of mortality outcomes, including federal guidance as operationalized in the HEI-2010, Harvard's Healthy Eating Plate as captured in the AHEI-2010, a Mediterranean diet as adapted in an Americanized aMED, and the DASH Eating Plan as included in the DASH score.

Project description:Background:Diet-quality indexes have been associated with a lower risk of chronic disease mortality in Western populations, but it is unclear whether these indexes reflect protective dietary patterns in Asian populations. Objective:We examined the association between Alternative Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), and Healthy Diet Indicator (HDI) scores and the risk of all-cause cardiovascular disease (CVD), cancer, and respiratory disease mortality. Methods:We used data from a prospective cohort of 57,078 Singapore Chinese men and women (aged 45-74 y) who were free of cancer and CVD at baseline (1993-1998) and who were followed up through 2014. The diet-quality index scores were calculated on the basis of data from a validated 165-item food-frequency questionnaire. Cox regression models with adjustment for potential confounders including sociodemographic and lifestyle variables, body mass index, and medical history were used to estimate HRs and 95% CIs. Results:During a total of 981,980 person-years of follow-up, 15,262 deaths (CVD: 4871; respiratory: 2690; and cancer: 5306) occurred. Comparing the highest with the lowest quintiles, the multivariable adjusted HRs (95% CIs) for all-cause mortality were 0.82 (0.78, 0.86) for AHEI-2010, 0.80 (0.76, 0.85) for aMED, 0.80 (0.75, 0.84) for DASH, and 0.88 (0.83, 0.92) for HDI scores (all P-trend < 0.001). Higher diet index scores were associated with a 14-28% lower risk of CVD and respiratory mortality, but only a 5-12% lower risk of cancer mortality. Higher consumption of vegetables, fruit, nuts, and long-chain n-3 (?-3) fatty acids, lower consumption of red meat, and avoidance of high alcohol consumption were the diet index components associated with a lower risk of mortality. Conclusion:Adherence to several recommended dietary patterns that emphasize healthy plant-based foods was associated with a substantially lower risk of chronic disease mortality in an Asian population. The Singapore Chinese Health Study was registered at www.clinicaltrials.gov as NCT03356340.

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Proteins as Mediators of the Association Between Diet Quality and Incident Cardiovascular Disease and All-Cause Mortality: The Framingham Heart Study.

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