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)

Abstract

ObjectivesDoubt has been cast on the atheroprotective effect of very high high-density lipoprotein cholesterol (HDL-C). Hypertensive retinopathy (HR) is caused by persistent systemic hypertension. Therefore, we aimed to investigate the association between extremely high HDL-C (EH-HDL) and HR.DesignA cross-sectional study.ParticipantsA total of 4072 general Japanese population aged 40–74 years who underwent regular medical check-ups including fundus examinations.Outcome measuresHR and clinical parameters including serum HDL-C were investigated. HR was determined by the Keith-Wagener classification and the Scheie classifications for Hypertension and Atherosclerosis (n=4054 available). Serum HDL-C was divided into five categories: 30–49, 50–69, 70–89, 90–109 and ≥110 mg/dL.ResultsOverall, 828 (20.3%) subjects had Keith-Wagener-HR, 578 (14.3%) had hypertension-HR, and 628 (15.5%) had atherosclerosis-HR. Blood pressure decreased as HDL-C level increased, whereas the prevalences of HRs showed U-shaped curves against HDL-C with minimum values for HDL-C 90–109 mg/dL. In logistic regression analyses, EH-HDL ≥110 mg/dL was significantly associated with Keith-Wagener-HR and atherosclerosis-HR, compared with HDL-C 90–109 mg/dL after adjustments for age, sex and systolic blood pressure (OR 3.01, 95% CI 1.45 to 6.27 and OR 2.23, 95% CI 1.03 to 4.86). The hypertension-HR was not significantly associated with EH-HDL regardless of adjustment for the confounding factors (p=0.05–0.08). Although serum HDL-C as a continuous variable was inversely associated with three HRs, which disappeared after adjustment for the confounding factors.ConclusionEH-HDL may be associated with HR independently of blood pressure, suggesting that EH-HDL reflects a special atherosclerotic condition.

The Association Between Lipid Profile and Subfoveal Choroidal Thickness in Chinese Patients with Proliferative Diabetic Retinopathy Secondary to Type 2 Diabetes

“…A meta-analysis by Wang et al 72 showed a significantly positive association between HDL-C and AMD, suggesting people with high HDL-C levels may be at an increased risk for AMD. In addition to AMD, HDL-C is also significantly associated with hypertensive retinopathy, 36 suggesting extremely high HDL reflects a specific atherosclerotic condition. A plausible explanation for this discrepancy is that HDL-C can be modified via myeloperoxidase-associated mechanisms under certain conditions, thus losing its protective effect and becoming atherogenic.…”

U-Shaped Relationship Between Proteinuria and High-Density Lipoprotein Cholesterol: Results of Cross-Sectional and Six Years Cohort Studies (KITCHEN-10)

“…In recent years, we have demonstrated the association of extremely high HDL-C, mostly defined as > 100 mg/dL, with diabetes [17], high blood pressure [18], and hypertensive retinopathy [31]. All of these are well-known risk factors for the incidence of kidney disease and proteinuria [1,2,4].…”

Association of Serum High-Density Lipoprotein Cholesterol with High Blood Pressures at Checkup: Results of Kanagawa Investigation of Total Checkup Data from the National Database-9 (KITCHEN-9)

“…To date, three studies addressed the association between HDL-C concentration and hypertension [ 22 , 23 , 24 ]. Additionally, we recently showed an association between extremely high HDL-C (≥110 mg/dL) and hypertensive retinopathy in a general population who underwent fundus examinations [ 25 ]. Our results suggested a positive association between HDL-C concentration and blood pressure/hypertension-related pathology.…”

“…Our results suggested a positive association between HDL-C concentration and blood pressure/hypertension-related pathology. However, these four studies [ 22 , 23 , 24 , 25 ], which examined the pathophysiology of very low and high HDL-C concentrations (e.g., <30 mg/dL and ≥90 mg/dL), consisted of relatively small sample sizes (<5000 participants in total). Actually, the number of subjects with hypertensive retinopathy was only 16 in the extremely high HDL-C group in our previous study [ 25 ].…”

“…However, these four studies [ 22 , 23 , 24 , 25 ], which examined the pathophysiology of very low and high HDL-C concentrations (e.g., <30 mg/dL and ≥90 mg/dL), consisted of relatively small sample sizes (<5000 participants in total). Actually, the number of subjects with hypertensive retinopathy was only 16 in the extremely high HDL-C group in our previous study [ 25 ]. Consequently, it was difficult to conduct an appropriate statistical analysis with proper adjustment for relevant confounding factors (covariates) in the low and very high HDL-C groups, which hampered disclosure of a latent overall association between HDL-C concentration and hypertension.…”