Is high-density lipoprotein a modifiable treatment target or just a biomarker for cardiovascular disease?

Whyte, Martin

doi:10.1177/2048004019869736

Cited by 5 publications

(5 citation statements)

References 58 publications

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“…Previous studies have shown that larger HDL particles seem to protect against atherogenesis, while the smaller subclasses are positively correlated with the risk of CVD [19,[34][35][36][37][38][39][40][41][42][43][44]. When measuring HDL-C by traditional methods, the positive and negative associations of small and large HDL particles may counteract each other.…”

Section: Hdl-subfractionsmentioning

confidence: 99%

Atherogenic lipidomics profile in healthy individuals with low cardiorespiratory fitness: The HUNT3 fitness study

et al. 2022

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Section: Hdl-subfractionsmentioning

confidence: 99%

Atherogenic lipidomics profile in healthy individuals with low cardiorespiratory fitness: The HUNT3 fitness study

et al. 2022

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“…Furthermore, in the past decade, several studies have shown that extremely high HDL-C is associated with elevated mortality [12][13][14][15][16]. Additionally, increased HDL-C owing to the use of cholesteryl ester transfer protein (CETP) inhibitors does not protect against the incidence of cardiovascular disease or mortality [32][33][34][35]. Although genetic variation in CETP is a major determination for high HDL-C in Japan [36,37], such genetic information was not investigated in this study.…”

Section: Discussionmentioning

confidence: 94%

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

Igata

Nakajima

2022

J Clin Med Res

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Background: Although a very high level of high-density lipoprotein cholesterol (HDL-C) may be a potential cardiovascular disease risk factor, the detail and underlying mechanism remain unclear. Therefore, we examined the associations of serum HDL-C with the incidence of proteinuria, a predictor for cardiovascular disease, in a community-based study. Methods:We investigated clinical parameters, including serum HDL-C and proteinuria, among 1,191,409 people aged 40 -74 years who underwent a health checkup in a cross-sectional study. In the cohort study, the incidence of proteinuria after 6 years was investigated in 451,987 participants without proteinuria at baseline, who were simultaneously enrolled in the cross-sectional study. Results:The prevalence of proteinuria showed a U-shaped relationship with 10 HDL-C categories, with a minimum of 60 -89 mg/dL in the cross-sectional study. Logistic regression analysis showed similar U-shaped relationships between odds ratios for proteinuria and HDL-C categories, with a minimum of 70 -79 mg/dL. The associations between very high HDL-C (≥ 90 mg/dL) and proteinuria were strengthened after adjustment for body mass index (BMI). In the cohort study, a crude L-shaped relationship was observed between the incidence of proteinuria and baseline HDL-C, which turned into U-shaped relationship after adjustment for baseline BMI and HDL-C after 6 years.Conclusions: Low and very high levels of HDL-C may be associated with the incidence of proteinuria, and BMI may be a potent contributing factor to the underlying mechanism.

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“…For the last decade, several trials to raise HDL-C concentrations pharmacologically by inhibiting the cholesteryl ester transfer protein were mostly unsuccessful in the prevention of CVD [13,14,15], suggesting that some factors beyond HDL-C concentration per se may be responsible for the increased risks of CVD. In the current results, the underlying mechanism between extremely high HDL-C and impaired glucose metabolism, a well-known risk for CVD, remains unknown, although participants with extremely high HDL-C levels had favorable profiles for weight, lipids, exercise, and smoking.…”

Section: Discussionmentioning

confidence: 99%

Impaired Glucose Metabolism in People with Extremely Elevated High-Density Lipoprotein Cholesterol and Low Alcohol Consumption: Results of the Kanagawa Investigation of Total Checkup Data from the National Database-3 (KITCHEN-3)

Nakajima

Higuchi

2019

JCM

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Background: Recently, we have shown that extremely high high-density lipoprotein cholesterol (HDL-C), which was observed mostly in heavy drinkers, was associated with the incidence of diabetes. However, the observed association was influenced by the consumption of alcohol. Furthermore, it is unknown whether impaired glucose metabolism exists in people with extremely high HDL-C, regardless of their alcohol consumption. Therefore, we addressed this issue in people who did not have a habit of drinking alcohol. Methods: In this community-based cross-sectional study, we included 177,034 participants (40–74 years old) who reported being nondrinkers. We investigated levels of HbA1c, fasting plasma glucose (FPG), HDL-C, and clinical parameters according to 11 levels of HDL-C concentration from 20 to 120 mg/dL or over. Results: A total of 6112 participants with HDL-C ≥ 100 mg/dL (3.5%) showed a better lipid profile, higher prevalence amongst women, more habitual exercise, a lower prevalence of smoking, and lower body mass index (BMI). Compared with an HDL-C of 70–79 mg/dL, HDL-C ≤ 69 mg/dL (except an HDL-C of 20–29 mg/dL) and HDL-C ≥ 90 mg/dL were significantly associated with a high HbA1c of ≥6.0%, independently of confounding factors. This finding was distinctly demonstrated in women. Similar trends were observed when high HbA1c was replaced with high FPG (≥110 mg/dL). Conclusions: Our study demonstrated that impaired glucose metabolism may exist in people with extremely high HDL-C and who hardly drink alcohol.

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Is high-density lipoprotein a modifiable treatment target or just a biomarker for cardiovascular disease?

Cited by 5 publications

References 58 publications

Atherogenic lipidomics profile in healthy individuals with low cardiorespiratory fitness: The HUNT3 fitness study

Atherogenic lipidomics profile in healthy individuals with low cardiorespiratory fitness: The HUNT3 fitness study

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

Impaired Glucose Metabolism in People with Extremely Elevated High-Density Lipoprotein Cholesterol and Low Alcohol Consumption: Results of the Kanagawa Investigation of Total Checkup Data from the National Database-3 (KITCHEN-3)

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