This large-scale cohort study on community-dwelling Koreans without diabetes over a 50-month period found that higher TG/HDL-C values were associated with IHD incidence, which remained after adjustment for lifestyle factors, inflammation, and hypertension medication. Moreover, compared with metabolic syndrome, TG/HDL-C had a more powerful predictive value for IHD.
The association between TG/HDL-C and incident IHD was more prominent in women than in men. Additionally, the HRs of incident IHD in women significantly increased according to the TG/HDL-C quartiles; contrastingly, those in men did not exhibit significant trends. Cheng et al. conducted a prospective study on 11,946 Chinese individuals without diabetes found that the risk for type 2 diabetes increased by approximately 30% with 1-unit of the TG/HDL-C increment [8]. Moreover, they observed a clearer dose-response relationship in women than in men. Regarding cardiovascular disease (CVD), studies conducted in men and women separately have established this relationship. Hadaegh et al. showed that Iranian men in the highest TG/HDL-C quartile had a 1.75-fold higher risk of coronary heart disease over a median follow-up period of 6.5 years compared with the reference low quartile [20]. Another longitudinal study conducted by Bittner et al. reported a positive relationship between the TG/HDL-C and suspected CVD mortality in 554 US women over a median period of 6 years [15]. The former and latter studies on men and women, respectively, reported a fourth quartile cut point of 6.9 and 2.8, respectively. Recent studies on TG/HDL-C have reported that it is associated with long-term mortality in high-risk individuals who have undergone percutaneous coronary angiography [21], as well as the relevance of subclinical coronary arterial calcification in low-risk individuals without diabetes [11]. However, these studies did not address sex differences. Another study reported that TG/HDL-C, but not the LDL-C to HDL-C ratio, in women has a significant predictive value for CVD in a population-based cross-sectional study, unlike in men [22]. Therefore, it may be advantageous for assessing and managing TG/HDL-C differently in men and women.
There was a noticeable increase and decrease in TG and HDL-C, respectively, with insulin resistance progression; moreover, the TG/HDL-c ratio is useful for assessing early insulin resistance [6, 23]. High TG and low HDL-C are the two most common lipid abnormalities among Korean adults aged > 20 years, with a prevalence of approximately 28.7% and 41.2%, respectively [24]. The Korea National Health and Nutrition Examination Survey indicated an increase in both high TG and low HDL-C by > 30% in 2010 compared with 2007. In the United States, approximately 30% and 40% of adult men /women in their 20s and 30s, respectively, have high TG and/or low HDL-C [25]. Individuals with insulin resistance are more susceptible to atherosclerosis; moreover, coronary arterial disease can develop and progress from early insulin resistance [5, 26]. The atherogenic link between TG/HDL-C and IHD, besides insulin resistance, is associated with the generation of small, dense LDL particles, which can cause vascular compromise [9, 27]. The NCEP guidelines for metabolic syndrome indicate well-established sex differences in the HDL-C level [28]. In the same context, the TG/HDL-C ratio was significantly higher in men; however, its association with IHD was more pronounced in women.
A major strength of our study was that this was a longitudinal large-scale study linked to HIRA data, which are based on the universal coverage system in Korea. This decreases the chance of missing data. This study has several limitations. First, given that the study cohort comprised volunteers for health promotion screenings conducted at a single hospital, the participants could have been slightly healthier than the general Korean population. Moreover, some confounding variables, including dietary data, may have not been initially assessed. Second, some individuals with diabetes may have been included in the final analysis since hemoglobin A1c assessment and oral glucose tolerance tests were not performed at the beginning of the study.