Novel Classification of Cardiovascular Disease Subtypes Reveals Associations Between Mortality and Polyunsaturated Fatty Acids: Insights from the United Kingdom Biobank Study

Background: Traditional association studies of cardiovascular disease (CVD) categorizations and polyunsaturated fatty acids (PUFAs) yielded conflicting fl icting fi ndings. We propose a novel classification fi cation system based on fundamental characteristics of cardiovascular patients, such as age, body mass index, waist-hip - hip ratio, to more accurately assess the impact of PUFAs (plasma measures) such as omega (to) to )-3 (n-3) - 3) and to-6 on mortality in cardiovascular patients. Methods: Principal component analysis and k-means clustering were used to determine the CVD subtype. Variables included age, body mass index, waist-hip - hip ratio, diastolic blood pressure, systolic blood pressure, total cholesterol, total triglycerides, high-density lipoprotein- cholesterol, apolipoprotein B:apolipoprotein A1, glycated hemoglobin, creatinine, albumin, C-reactive protein, white blood cell count, platelet count, and hemoglobin concentration. The association of PUFAs with all-cause, cardiovascular, and ischemic heart disease (IHD) mortality in patients with CVD was prospectively evaluated using restricted cubic splines and Cox proportional risk models. Results: Among the 35,096 participants, 3,786 fatalities occurred. Three distinct CVD subtypes were identified, fi ed, with cluster 3 characterized by older age, male gender, and low high-density lipoprotein-cholesterol, having the highest risk of mortality. Clusters 2 and 3 had the highest DHA and to-6/ to-3 ratios, respectively, compared with Cluster 1. The protective effects of total PUFAs, to-3, and DHA were mainly reflected fl ected in all-cause mortality and were more significant fi cant in clusters 2 and 3. Furthermore, the to-6/ to-3 ratio of the highest quartile increased risk of all-cause [Q3: hazard ratio (HR): 1.14, 95% confidence fi dence interval [CI]: 1.00, 1.29; Q4: HR: 1.41, 95% CI: 1.24, 1.61], CVD (Q4: HR: 1.36, 95% CI: 1.07, 1.75), and IHD mortality (Q4: HR: 1.17, 95% CI: 1.12, 2.03) in cluster 3 compared with the fi rst quartile. Conclusions: Our fi ndings highlight the heterogeneity of associations observed for the same type of PUFAs across distinct clusters. This association may be elucidated by the intricate interplay of various factors, encompassing inflammation, fl ammation, lipid metabolism, and cardiovascular health.