Association of extremely high levels of high-density lipoprotein cholesterol with cardiovascular mortality in a pooled analysis of 9 cohort studies including 43,407 individuals: The EPOCH–JAPAN study

Hirata, Aya; Sugiyama, Daisuke; Watanabe, Makoto; Kotani, Kazuhiko; Ueshima, Hirotsugu; Imai, Yutaka; Ohkubo, Takayoshi; Irie, Fujiko; Iso, Hiroyasu; Kitamura, Akihiko; Ninomiya, Toshiharu; Kiyohara, Yutaka; Miura, Katsuyuki; Murakami, Yoshitaka; Nakagawa, Hideaki; Nakayama, Takeo; Okayama, Akira; Sairenchi, Toshimi; Saitoh, Shigeyuki; Sakata, Kiyomi; Tamakoshi, Akiko; Tsuji, Ichiro; Yamada, Michiko; Kiyama, Masahiko; Miyamoto, Yoshihiro; Ishikawa, Shizukiyo; Yatsuya, Hiroshi; Okamura, Tomonori

doi:10.1016/j.jacl.2018.01.014

Cited by 112 publications

(142 citation statements)

References 47 publications

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“…Experimental studies reported that HDL-C could be cardio-protective due to its effect of reverse cholesterol transport [2], inhibition of LDL oxidation [3] and reactive oxygen species [4,5], inhibition of adhesion molecule expression [6], antiapoptotic [7], anticoagulant [8,9], antiinfectious [10] and vasodilatory actions [11]. Consistently, previous observational studies reported an inverse or a U-shaped association between HDL-C concentrations and CVD morbidity and mortality in general populations [12,13]. However, clinical trials showed that signi cant increases in HDL-C concentrations due to the cholesteryl ester transfer protein inhibitors and other lipid modifying drugs (e.g., feno brate and niacin) failed to reduce future CVD risk [14][15][16][17].…”

Section: Introductionmentioning

confidence: 60%

Different Associations between High Density Lipoprotein Cholesterol and Cardiovascular Diseases in Diabetic and Non-diabetic People: A Prospective Community-based Study

Huang

Lichtenstein

et al. 2020

Preprint

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Abstract Background: Experimental studies found that the functionality of high density lipoprotein cholesterol (HDL-C) may be lost in the presence of diabetes mellitus (DM). We prospectively tested whether DM modified the association between HDL-C concentrations and cardiovascular disease (CVD).Methods: Included were 91,354 Chinese adults (8,244 participants with DM and 83,110 participants without DM) without use of lipid-lowering drugs and free of CVD or cancer at baseline (2006). The primary endpoint of interest was a composite of CVD (myocardial infarction, ischemic stroke and hemorrhagic stroke). Cumulative average HDL-C concentrations were calculated from all available HDL-C measures at baseline (2006) and during the follow-up period (2008, 2010, 2012 and 2014).Results: During a mean of 10.4 year of follow-up, there were 5,076 CVD events identified. Presence of DM significantly modified the association between HDL-C concentrations and CVD risk (Pinteraction =0.003). The association between HDL-C concentrations and CVD followed a U-shaped curve in individuals without DM (Pnonlinearity <0.001). The adjusted hazard ratio (HR) of CVD was 1.25 (95% confidence interval (CI): 1.06-1.48) for HDL-C concentrations <1.04 mmol/L and 1.80 (95% CI: 1.56-2.07) for HDL-C concentrations >2.07 mmol/L, relative to the lowest risk group (HDL-C concentrations of 1.30-1.42mmol/L). In participants with DM, higher HDL-C concentrations were associated with a higher risk of CVD, in a dose-response manner (Pnonlinearity =0.44; Ptrend <0.001). The adjusted HR of CVD was 1.63 (95%CI: 1.20-2.20) for HDL-C concentrations >2.07 mmol/L, relative to HDL-C concentrations of 1.30-1.42mmol/L. Conclusion: High HDL-C concentrations were paradoxically associated with increased risk of composite CVD outcomes in individuals with or without DM. However, low HDL-C concentrations failed to predict future CVD risk in individuals with DM.

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Section: Introductionmentioning

confidence: 60%

Different Associations between High Density Lipoprotein Cholesterol and Cardiovascular Diseases in Diabetic and Non-diabetic People: A Prospective Community-based Study

Huang

Lichtenstein

et al. 2020

Preprint

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“…19 Hirata et al also demonstrated association of extremely high HDL-C with increased atherosclerotic cardiovascular disease (including CAD and stroke) mortality. 20 Although there is no clear explanation for the association of extremely high HDL-C and cardiovascular mortality, investigators suggested a possible genetic variant such as cholesterylester transfer protein (CETP) gene mutation. CETP gene is known to be responsible for HDL-C metabolism, and its polymorphism has been suggested to be associated with accelerated atherosclerosis and cardiovascular risk.…”

Section: Discussionmentioning

confidence: 94%

“…Madsen et al found U‐shaped association between HDL‐C level and all‐cause mortality and concluded that extremely high HDL‐C paradoxically increases all‐cause mortality . Hirata et al also demonstrated association of extremely high HDL‐C with increased atherosclerotic cardiovascular disease (including CAD and stroke) mortality . Although there is no clear explanation for the association of extremely high HDL‐C and cardiovascular mortality, investigators suggested a possible genetic variant such as cholesterylester transfer protein (CETP) gene mutation.…”

Section: Discussionmentioning

confidence: 99%

Primary biliary cholangitis presenting as acute ischemic stroke: A rare association

Park

Islam

Vemulapalli

et al. 2020

Clinical Case Reports

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“…Furthermore, in a very recent study of two large population-based cohorts in Denmark (52,268 men and 64,240 women), it was clearly shown that in men and women in the general population extremely high HDL-C levels were paradoxically associated with high all-cause mortality risk [35] . In addition, in a large-scale pooled analysis of 9 Japanese cohorts, which included 43,407 participants, it was again shown that extremely high HDL-C levels led to an increase of atherosclerotic CVD mortality [36] .…”

Section: Impact Of Dysfunctional Hdl On Cvdmentioning

confidence: 96%

Dysfunctional high-density lipoprotein and atherogenesis

Kosmas¹,

Silverio²,

Sourlas³

et al. 2019

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High-density lipoprotein (HDL) plays a major role in reverse cholesterol transport (RCT) but also exhibits, antiinflammatory, endothelial/vasodilatory, anti-thrombotic, antioxidant, anti-aggregating, anticoagulant and cytoprotective functions, which enhance its protective effect against cardiovascular disease. However, the function of HDL is dependent upon genetic, environmental and lifestyle factors. Modification of the protein or lipid components of HDL in certain conditions may convert the HDL particles from anti-inflammatory to pro-inflammatory and pro-atherogenic by limiting their ability to promote RCT and to prevent LDL modification. In our review, we will present the clinical and scientific data pertaining to the factors and conditions that impair HDL functionality and we will discuss the effects of dysfunctional HDL on atherogenesis.

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Association of extremely high levels of high-density lipoprotein cholesterol with cardiovascular mortality in a pooled analysis of 9 cohort studies including 43,407 individuals: The EPOCH–JAPAN study

Cited by 112 publications

References 47 publications

Different Associations between High Density Lipoprotein Cholesterol and Cardiovascular Diseases in Diabetic and Non-diabetic People: A Prospective Community-based Study

Different Associations between High Density Lipoprotein Cholesterol and Cardiovascular Diseases in Diabetic and Non-diabetic People: A Prospective Community-based Study

Primary biliary cholangitis presenting as acute ischemic stroke: A rare association

Dysfunctional high-density lipoprotein and atherogenesis

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