Coronary artery calcification (CAC) score used to quantify the degree of carotid artery plaque has demonstrated incremental prognostic value over conventional CVRFs 14, 15, especially in females with a low FRS 16. Imaging remains the gold standard for detection of SA, either via carotid intima-media thickness (IMT) measurements 12 or carotid artery plaque detection 13. However, direct comparisons of the two models proved the RRS to be a more accurate short-term predictor but with modest overall gains 11. The Reynolds Risk Score (RRS) was specifically developed for women and helped reclassify those initially deemed to be low risk using the FRS model. Even though the Framingham risk equation factors in gender, it often classifies asymptomatic women as being low-risk, even in the presence of significant coronary artery disease 8. While FRS is known to underestimate risk of CHD in women 8, there is a lack of improved gender-specific risk stratification strategies to supplement the FRS. Although much of this cardio-protection is attributed to the beneficial effects of estrogen, the failure of hormone replacement therapy to decrease CHD highlights the complex relationship shared between atherosclerosis process and biological sex 10. Past epidemiological studies reported that symptomatic atherosclerosis typically manifests a decade later in women compared to men, while myocardial infarction incidents are delayed by approximately 5–10 years 9. Hence, FRS has limited predictive value to forecast CHD incidence in low FRS (< 10%) populations, particularly in younger adults and women 8. While this assessment is well validated in elderly people and in men, there is increasing evidence of subclinical atherosclerosis (SA) and CVD even in populations with low conventional CVRF burden 6, 7. FRS considers CVRFs, age and gender to predict the 10-year risk of developing CHD and is the most common clinical metric used to identify high-risk individuals 5. The Framingham Risk Score (FRS) epitomizes an important advancement in coronary heart disease (CHD) prevention. The likelihood of future cardiovascular events in asymptomatic individuals is typically estimated using conventional cardiovascular risk factors (CVRF) such as cigarette smoking, diabetes status, hyperlipidemia, and hypertension 4. To mitigate disease burden, there are contemporary prediction tools that provide differential and individualized clinical insights into CVD development. This results in a smaller workforce and incurring greater healthcare expenditure, subsequently taxing the Singapore economy 3. In 2019 alone, nearly 1 in 3 deaths in Singapore was caused by CVD 1. We report novel postprandial models for predicting subclinical atherosclerosis in apparently healthy Asian subjects using a gender-specific approach, complementing the conventional Framingham Risk Score.Ĭlinical Trial Registration: The trial was registered at as NCT03531879.Ĭardiovascular disease (CVD) is responsible for a significant proportion of morbidity and mortality in Singapore over the last three decades 1, 2. We used gender-specific association with different combinations of postprandial predictors to develop 2 models for predicting risk of subclinical atherosclerosis in males (ROC AUC = 0.7867, 95% CI 0.6567, 0.9166) and females (ROC AUC = 0.9161, 95% CI 0.8340, 0.9982) respectively. Distinctive gender differences in postprandial trajectories of glucose, lipids and inflammatory markers were observed. Prediction models were developed using logistic regression and subsequently subjected to cross-validation to obtain a de-optimized receiver operating characteristic (ROC) curve. Subjects underwent cardiovascular imaging and postprandial blood phenotyping after consuming a standardized macronutrient meal. A total of 101 healthy Chinese subjects (46 females, 55 males) at low risk of coronary heart disease completed the study. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis. Gender-specific markers to predict cardiovascular risk in overtly healthy people are lacking. The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women.
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