Very High Levels of High-Density Lipoprotein Cholesterol and Cardiovascular Events in Japanese Population

High Incidence of Diabetes in People with Extremely High High-Density Lipoprotein Cholesterol: Results of the Kanagawa Investigation of Total Checkup Data from the National Database-1 (KITCHEN-1)

“…This finding was made for the first time using a very large database of health check data obtained for people across the entire Kanagawa prefecture, which has the second-largest population in Japan, next to Tokyo. Furthermore, we have determined a provisional reference level of HDL-C, which, at least in terms of diabetes risk, may be higher than previously used for CVD: possibly around 80–89 mg/dL, rather than 60–70 mg/dL [15,20]. Intriguingly, and consistent with our results, two previous studies conducted in Japan [22,31] have shown that individuals with a high HDL-C (≥90 or 100 mg/dL) were more likely to have diabetes or high FPG (≥100 mg/dL) than those with an HDL-C of 80–89 mg/dL, although statistically significant differences were not described.…”

“…Thus, a concentration of HDL-C of >80 mg/dL, which has been conventionally considered to be very high, may not actually be “very high”, but instead only relatively high or indeed an optimal concentration of HDL-C. In addition, previous clinical studies that have been considered large were unlikely to be sufficiently powered for the detailed analysis of participants with very high HDL-C (e.g., ≥80 mg/dL) [15,18], meaning that the categories in our study that represent a provisional optimal HDL-C and an extremely high HDL-C had been previously combined. Consequently, the impact of extremely high HDL-C on the incidence of CVD could not be appropriately evaluated.…”

“…During the last decade, doubt has been cast on the protective effect of very high HDL-C against CVD [15,16,17]. Large cohort studies have shown that higher mortality rates associated with CVD, including due to myocardial infarction and stroke, are observed in individuals with HDL-C values over 80–100 mg/dL [18,19,20,21,22].…”

Association between extremely high high-density lipoprotein-cholesterol and hypertensive retinopathy: results of a cross-sectional study from Kanagawa Investigation of Total Checkup Data from the National Database-6 (KITCHEN-6)

“…Simultaneously, the present results suggest that the optimal HDL-C level is approximately 90–109 mg/dL, which is a little higher than the finding in our previous studies (70–89 mg/dL), 8 9 and much higher than traditionally thought (60–70 mg/dL). 1 5 A plausible explanation for this discrepancy is that the present analysis was not conducted according to male and female sex because of the small sample size in the high HDL-C groups and thus the high prevalence of women, who have higher HDL-C level than men, 4–6 in the high HDL-C groups may have raised the optimal HDL-C level to a higher level as a whole. In this study, the mean HDL-C level in women was 72.0 mg/dL, which is already beyond the traditionally established high level (60–70 mg/dL).…”

“…During the last decade, doubt has been cast on the atheroprotective effect of very high high-density lipoprotein cholesterol (HDL-C) against cardiovascular disease (CVD). [1][2][3] Consistently, cohort studies in recent years have shown that higher mortality rates associated with CVD are observed in individuals with HDL-C levels above 80-100 mg/dL. [4][5][6][7] In addition, we recently demonstrated that people with extremely high HDL-C (EH-HDL; ≥110 mg/dL) have increased risks for diabetes 8 and impaired glucose metabolism equivalent to pre-diabetes, 9 compared with HDL-C 80-89 and 70-79 mg/dL, respectively, which showed a J-shaped or U-shaped association between the levels of HDL-C and impaired glucose metabolism.…”