HDL-C is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response fashion: a pooled analysis of 37 prospective cohort studies

Zhong, Guo‐Chao; Huang, Su-Qun; Yang, Peng; Wan, Lun; Wu, You‐Qi‐Le; Hu, Tianyang; Hu, Jie‐Jun; Hao, Fa‐Bao

doi:10.1177/2047487320914756

Cited by 86 publications

(78 citation statements)

References 75 publications

(232 reference statements)

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“…The study indicated that both the lowest and highest HDL-C levels were related to increased all-cause and cardiovascular mortality risk. 15 Similarly, Sun et al found that, in the general Chinese adults, the relation of HDL-C and allcause mortality was U-shaped and that HDL-C≥80 mg/dl was significantly correlated with greater risk of all-cause death. 20 Another study using data from the NHANES 1999-2010 showed that extremely high (≥100 mg/dL) or low (<30 mg/dL) levels increased risk of all-cause deaths and deaths from coronary heart disease and stroke in American adults, but the results were not stratified by hypertension status.…”

Section: Discussionmentioning

confidence: 95%

“…For example, a J-shaped or U-shaped association between HDL-C and allcause mortality or cardiovascular mortality was observed in the general population. [15][16][17][18][19] In addition, a cohort study from China found that both lower and higher HDL-C were associated with increased risk of CVDs in the general rural China population, but results for cardiovascular mortality were not significant. 20 In patients with type 2 diabetes, participants with relatively high HDL-C concentration had higher risk of CVDs and all-cause mortality.…”

Section: Introductionmentioning

confidence: 99%

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<p>U-Shaped Association of High-Density Lipoprotein Cholesterol with All-Cause and Cardiovascular Mortality in Hypertensive Population</p>

Chen¹,

Liu²,

Liu³

et al. 2020

RMHP

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Purpose: Whether the paradox of high-density lipoprotein cholesterol (HDL-C) and elevated mortality risk extends to hypertensive patients is unclear. We aimed to investigate the association between HDL-C and all-cause and cardiovascular disease mortality in adults with hypertension. Methods: In the National Health and Nutrition Examination Surveys, 11,497 hypertensive participants aged ≥18years old and examined at baseline between 1999 and 2014 were followed up until December 2015. We categorized the HDL-C concentration as ≤30, 31-40, 41-50, 51-60 (reference), 61-70, >70 mg/dL and examined their associations with all-cause and cardiovascular mortality, respectively. Multivariate Cox regression was used to calculated hazard ratio (HR) and 95% confidence interval (CI) for mortality risk. Results: During follow-up (median: 9.2 ± 3.8 years), 3012 deaths and 713 cardiovascular deaths were observed. In the restrictive cubic curves, associations of HDL-C levels and allcause and cardiovascular mortality were detected to be U-shaped. After multivariable adjustment, HRs for all-cause mortality were for the lowest HDL-C concentration (≤30 mg/dL) 1.29 (95% CI, 1.07-1.56) and the highest (>70 mg/dL) 1.20 (1.06-1.37), comparing with the reference group. For cardiovascular mortality, HRs were 1.31 (0.83-1.48) and 1.09 (0.83-1.43), respectively. Similar results were obtained in subgroups stratified by age, gender, race, and taking lipid-lowering drugs. The lowest all-cause mortality risk was observed at HDL-C 66 mg/dL (concentration) and 51-60 mg/dL (range). Conclusion: Both lower and higher HDL-C concentration appeared to be associated with higher mortality in hypertensive population. Further investigation is warranted to clarify the underlying mechanisms.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

<p>U-Shaped Association of High-Density Lipoprotein Cholesterol with All-Cause and Cardiovascular Mortality in Hypertensive Population</p>

Chen¹,

Liu²,

Liu³

et al. 2020

RMHP

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“…Moreover, Zhong et al reported that both high and low HDL-C levels (ranging from 22 mg/dL to 97 mg/ dL) were associated with an increased risk of mortality from CAD [38]. The lncRNAs identified in this study provide insights into the potential molecular mechanisms underlying the effects of low HDL-C levels.…”

Section: Discussionmentioning

confidence: 70%

Microarray analysis of long non-coding RNA expression profiles in low high-density lipoprotein cholesterol disease

Wang

Guo

et al. 2020

Lipids Health Dis

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Background: Low high-density lipoprotein cholesterol (HDL-C) disease with unknown etiology has a high prevalence in the Xinjiang Kazak population. In this study, long noncoding RNAs (lncRNAs) that might play a role in low HDL-C disease were identified. Methods: Plasma samples from 10 eligible individuals with low HDL disease and 10 individuals with normal HDL-C levels were collected. The lncRNA profiles for 20 Xinjiang Kazak individuals were measured using microarray analysis. Results: Differentially expressed lncRNAs and mRNAs with fold-change values not less than 1.5 and FDR-adjusted Pvalues less than 0.05 were screened. Bioinformatic analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses, were used to determine relevant signaling pathways and predict potential target genes. In total, 381 lncRNAs and 370 mRNAs were differentially expressed based on microarray analysis. Compared with those in healthy individuals, several lncRNAs were upregulated or downregulated in patients with low HDL-C disease, among which TCONS_00006679 was most significantly upregulated and TCONS_00011823 was most significantly downregulated. GO and KEGG pathway analyses as well as co-expression networks of lncRNAs and mRNAs revealed that the platelet activation pathway and cardiovascular disease were associated with low HDL-C disease. Conclusions: Potential target genes integrin beta-3 (ITGB3) and thromboxane A2 receptor (TBXA2R) were regulated by the lncRNAs AP001033.3-201 and AC068234.2-202, respectively. Both genes were associated with cardiovascular disease and were involved in the platelet activation pathway. AP001033.3-201 and AC068234.2-202 were associated with low HDL-C disease and could play a role in platelet activation in cardiovascular disease. These results reveal the potential etiology of dyslipidemia in the Xinjiang Kazakh population and lay the foundation for further validation using large sample sizes.

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“…There are several studies investing the relationship between HDL-C and mortality conducted among general population in recent years ,most of which revealed J-shaped or U-shaped relationship (3-5, 22, 23). For example, Zhong et al (3)'s research demonstrated that in the general population, HDL-C level is associated with all-cause mortality in a J-shaped dose-response manner with the lowest risk observed at HDL-C levels of 54-58 mg/dL ; both extremely high and low HDL-C levels are associated with an increased risk of mortality. Mazidi et al(4) reported both extremely low(≤ 30 mg/dL) and extremely high(≥ 100 mg/dL) HDL-C levels were associated with greater risk of mortalities among American adults.…”

Section: Discussionmentioning

confidence: 99%

Association Between Serum High-Density Lipoprotein Cholesterol Concentration and Mortality in Critically Ill Patients: A Retrospective Cohort Study

Guo¹,

Zhi-yu²,

Qu³

et al. 2020

Preprint

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Background This research aims to explore the association between serum high-density lipoprotein cholesterol (HDL-C) and mortality in patients who are critically ill. MethodsThis was a retrospective cohort study. Data were extracted from an online database named ‘Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III)’. 3384 patients were included, 967 septic patients and 1380 patients with acute kidney injury (AKI) were screened from all the patients included. The association between HDL-C and hospital mortality in all patients, septic patients and AKI patients was evaluated using HDL-C as a design variable.Results Serum HDL-C (42.4±18.0 VS 45.0±15.2, P<0.001) concentration was significantly lower for non-survivors than survivors. An arc-shaped relationship between HDL-C and mortality was found for the whole group of patients and the AKI subgroup of patients with inflection point at around 30mg/dL; for septic patients, this relationship became ‘U’-shaped with inflection points at around 30mg/dL and 60mg/dL, respectively. Low HDL-C was associated with increased hospital and ICU mortality, longer ICU length of stay (LOS) and hospital LOS compared with medium HDL-C level for all included patients (p<0.01, all) while the differences between high HDL-C and medium HDL-C group were statistically nonsignificant. Similar patterns were found among AKI subgroup of patients. For the sepsis subgroup, low HDL-C group also showed higher hospital and ICU mortality rate (p<0.001, p=0.002, respectively); however, low HDL-C group did not show longer ICU LOS or hospital LOS. Multivariate logistic regression models showed only low HDL-C(<30mg/dL) were associated with increased hospital mortality in all three models(model 1 OR: 1.44, 95% CI 1.05 to 1.97, p=0.022 ; model 2 OR: 1.51, 95% CI 1.01 to 2.27, p=0.044; model 3 OR: 1.69, 95% CI 1.15 to 2.49, p=0.007). In all three models, age, mechanical ventilation use, Sequential Organ Failure Assessment (SOFA) score and Elixhauser comorbidity score were positively associated with mortality.Conclusions Low HDL-C is associated with increased mortality in patients who are critically ill.

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HDL-C is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response fashion: a pooled analysis of 37 prospective cohort studies

Cited by 86 publications

References 75 publications

<p>U-Shaped Association of High-Density Lipoprotein Cholesterol with All-Cause and Cardiovascular Mortality in Hypertensive Population</p>

<p>U-Shaped Association of High-Density Lipoprotein Cholesterol with All-Cause and Cardiovascular Mortality in Hypertensive Population</p>

Microarray analysis of long non-coding RNA expression profiles in low high-density lipoprotein cholesterol disease

Association Between Serum High-Density Lipoprotein Cholesterol Concentration and Mortality in Critically Ill Patients: A Retrospective Cohort Study

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