Variation in cardiovascular disease risk factors among older adults in the Hunter Community Study cohort: A comparison of diet quality versus polygenic risk score

Abstract

Background: The interplay between cardiovascular disease (CVD) genetic risk indexed by a polygenic risk score (PRS) and diet quality still requires further investigation amongst older adults or those with established or treated CVD. The present study aimed to evaluate the relative contribution of diet quality, measured using the Australian Recommended Food Score (ARFS) and PRS, with respect to explaining variation in plasma lipids CVD outcomes in the Hunter Cohort.

Methods: The study comprised a secondary analysis of cross-sectional data from the Hunter Cohort study. Single-nucleotide polymorphisms from previously derived polygenic scores (PGSs) for three lipid classes were obtained: low-density lipoprotein, high-density lipoprotein and triglycerides, as well as PRS for coronary artery disease (CAD) from the PGS catalogue. Regression modelling and odds ratios were used to determine associations between PRS, ARFS and CVD risk.

Results: In total, 1703 participants were included: mean ± SD age 66 ± 7.4 years, 51% female, mean ± SD total ARFS 28.1 ± 8 (out of 74). Total diet quality and vegetable subscale were not significantly associated with measured lipids. By contrast, PGS for each lipid demonstrated a markedly strong, statistically significant correlation with its respective measured lipid. There was a significant association between CAD PRS and 5/6 CVD phenotypes (all except atrial fibrillation), with the largest effect size shown with coronary bypass. Adding dietary intake as a covariate did not change this relationship.

Conclusions: Lipid PGS explained more variance in measured lipids than diet quality. However, the poor diet quality observed in the current cohort may have limited the ability to observe any beneficial effects. Future research should investigate whether the diet quality of older adults can be improved and also the effect of these improvements on changes in polygenic risk.

Keywords: Hunter Community Study; cardiovascular disease; cohort; diet quality; polygenic risk.

Figure 1

The relationship between diet, polygenic scores (PGSs) of lipids and measured lipids. (a) Scatterplots of distribution of measured triglycerides (TGs) relative to diet quality (Australian Recommended Food Score [ARFS]) and PGS of TGs. Grey shading around trend line denotes the 95% confidence interval (CI) from the linear model regressing either trait on the outcome of measured TGs. (b) Forest plot of the effect of a SD increase in the best performing polygenic score (PGS) for that lipid in three different models: (i) baseline = adjusted for age, sex, and five single nucleotide polymorphism derived principal components; (ii) diet adjusted = ARFS total score as an additional covariate to the first model; and (iii) diet + other confounders adjusted = smoking status, educational attainment, and statin usage in addition to covariates in the second model. Error bars represent 95% CIs of the beta coefficient

Figure 2

Distribution of coronary artery disease (CAD) polygenic risk score (PRS) in self‐reported cardiovascular disease cases and health controls. Kernel density estimation plot of the most significantly associated CAD PRS (metaGRS or LDpred, standardised to have SD units) for six cardiovascular disease phenotypes relative to participants who did not self‐report any of the phenotypes. For each plot, the cases are coloured, and the controls are grey

Figure 3

Effect size of diet and coronary artery disease polygenic risk score (PRS) per quartile of variable. Points denote the odds ratio (OR) estimate of that quartile relative to the lowest quartile (1, reference category), error bars denote 95% confidence intervals (CIs). Heart attack cases were compared to the following three cohorts: (a) participants with no self‐reported binary cardiovascular disease (CVD) phenotypes; (b) all other participants with relevant dietary data available; and (c) participants who self‐reported one or more other CVD phenotypes but not heart attack. ARFS, Australian Recommended Food Score, with the total and vegetable specific subscale tested

Figure 4

Summary of findings. ARFS, Australian Recommended Food Score; CVD, cardiovascular disease; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein