Dataset Information

The U-shaped association of non-high-density lipoprotein cholesterol with all-cause and cardiovascular mortality in general adult population.

ABSTRACT:

Background

Non-high-density lipoprotein cholesterol (non-HDL-C) has been associated with atherosclerosis. However, the association between non-HDL-C and mortality in adult population remains unclear. We intended to investigate the association of non-HDL-C with cardiovascular and all-cause mortality using national representative data.

Methods

The study included 32,405 participants from the National Health and Nutrition Examination Survey (1999-2014). Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2015. Multivariable-adjusted Cox regression models were used to evaluate hazard ratio (HR) and 95% confidence interval (CI) of non-HDL-C concentrations in quintiles. Two-piecewise linear regression and restricted cubic spline analyzes were performed to test dose-response associations.

Results

After a median follow-up of 98.40 months, 2,859 (8.82%) all-cause and 551 (1.70%) cardiovascular deaths occurred. Compared with the highest group, the multivariable-adjusted hazard ratio (HR) of the first quintile for all-cause mortality was 1.53 (95%CI, 1.35-1.74). Higher non-HDL-C above a cutoff value of 4.9 mmol/L was related with cardiovascular mortality (HR = 1.33, 95%CI, 1.13-1.57). A U-shaped relationship between non-HDL-C and all-cause mortality was found in spline analysis with a cutoff value around 4 mmol/L. Similar results in subgroups analyzes were found among male, non-white population, participants who were not taking lipid-lowering drugs, and with body mass index (BMI) <25 kg/m².

Conclusion

Our findings suggest a U-shaped association between non-HDL-C and mortality among adult population.

SUBMITTER: Huang Y

PROVIDER: S-EPMC9945232 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The U-shaped association of non-high-density lipoprotein cholesterol with all-cause and cardiovascular mortality in general adult population.

Huang Yu Y Yan Meng Qi MQ Zhou Dan D Chen Chao Lei CL Feng Ying Qing YQ

Frontiers in cardiovascular medicine 20230208

<h4>Background</h4>Non-high-density lipoprotein cholesterol (non-HDL-C) has been associated with atherosclerosis. However, the association between non-HDL-C and mortality in adult population remains unclear. We intended to investigate the association of non-HDL-C with cardiovascular and all-cause mortality using national representative data.<h4>Methods</h4>The study included 32,405 participants from the National Health and Nutrition Examination Survey (1999-2014). Mortality outcomes were ascerta ...[more]

PMID: 36844732

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Project description:Background Current cholesterol guidelines have recommended very low low-density lipoprotein cholesterol (LDL-C) treatment targets for people at high risk of cardiovascular disease (CVD). However, recent observational studies indicated that very low LDL-C levels may be associated with increased mortality and other adverse outcomes. The association between LDL-C levels and long-term risk of overall and cardiovascular mortality among the U.S. general population remains to be determined. Methods and Results This prospective cohort study included a nationally representative sample of 14 035 adults aged 18 years or older, who participated in the National Health and Nutrition Examination Survey III 1988-1994. LDL-C levels were divided into 6 categories: <70, 70-99.9, 100-129.9, 130-159.9, 160-189.9 and ≥190 mg/dL. Deaths and underlying causes of deaths were ascertained by linkage to death records through December 31, 2015. Weighted Cox proportional hazards regression models were used to estimate the hazard ratios (HR) of mortality outcomes and its 95% CIs. During 304 025 person-years of follow up (median follow-up 23.2 years), 4458 deaths occurred including 1243 deaths from CVD. At baseline, mean age was 41.5 years and 51.9% were women. Very low and very high levels of LDL-C were associated with increased mortality. After adjustment for age, sex, race and ethnicity, education, socioeconomic status, lifestyle factors, C-reactive protein, body mass index, and other cardiovascular risk factors, individuals with LDL-C<70 mg/dL, compared to those with LDL-C 100-129.9 mg/dL, had HRs of 1.45 (95% CI, 1.10-1.93) for all-cause mortality, 1.60 (95% CI, 1.01-2.54) for CVD mortality, and 4.04 (95% CI, 1.83-8.89) for stroke-specific mortality, but no increased risk of coronary heart disease mortality. Compared with those with LDL-C 100-129.9 mg/dL, individuals with LDL-C≥190 mg/dL had HRs of 1.49 (95% CI, 1.09-2.02) for CVD mortality, and 1.63 (95% CI, 1.12-2.39) for coronary heart disease mortality, but no increased risk of stroke mortality. Conclusions Both very low and very high LDL-C levels were associated with increased risks of CVD mortality. Very low LDL-C levels was also associated with the high risks of all-cause and stroke mortality. Further investigation is needed to elucidate the optimal range of LDL-C levels for CVD health in the general population.

Project description:BackgroundPrevious findings have indicated that elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) are associated with hypertension. We aim to explore whether higher RC levels may be associated with hypertension beyond LDL-C in the general US adult population.MethodsThis study included 10,842 adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Weighted multivariable logistic regression models were used to estimate the odds ratios (ORs) of hypertension for LDL-C and RC. We also performed analyses examining the association between hypertension and LDL-C vs. RC concordant/discordant groups.ResultsA total of 4,963 (41.54%, weighted) individuals had hypertension. The weighted median levels were LDL-C: 118mg/dL, RC: 20mg/dL. At lower LDL-C clinical cut-point, the proportion of discordantly high RC dramatically increased. After multivariable adjustment, log RC was associated with higher prevalence of hypertension [OR 2.54, 95% confidence interval (CI) 2.17-2.99]. Participants with the highest tertile of RC were more likely to have hypertension (OR 2.18; 95% CI 1.89-2.52) compared with those with the lowest tertile of RC. This association remained marked after including body mass index (BMI), LDL-C, high-density lipoprotein cholesterol (HDL-C) or triglycerides. The association between LDL-C and hypertension was absent after adjusting for BMI, RC or triglycerides. Compared with low LDL-C/low RC group, the discordant low LDL-C/high RC group was associated with hypertension (OR 2.04; 95% CI 1.72-2.42), whereas the high LDL-C/low RC group was not, regardless of BMI, HDL-C or triglycerides. Similar results were observed when examining discordance among different clinical cut-points, except for the cut-point of LDL-C 70 mg/dL and RC 13 mg/dL. To better understand the association, we performed an additional analysis, which showed that among participants with apolipoprotein B < median (92mg/dL), those with discordant RC ≥ median (20mg/dL) had significantly higher odds of having hypertension (OR 1.73; 95% CI 1.38-2.17).ConclusionRC was associated with hypertension beyond LDL-C in the general US adult population. This association went beyond increased triglycerides levels, and lipoproteins other than apoB may be involved.

Project description:BackgroundThe association and population heterogeneities between low-density lipoprotein cholesterol (LDL-C) and all-cause and cardiovascular mortality remain unknown. We aimed to examine the dose-dependent associations of LDL-C levels with specific types of cardiovascular disease (CVD) mortality and heterogeneities in the associations among different population subgroups.MethodsA total of 2,968,462 participants aged 35-75 years from China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) (2014-2019) were included. Cox proportional hazard models and Fine-Gray subdistribution hazard models were used to estimate associations between LDL-C categories (<70.0, 70.0-99.9, 100.0-129.9 [reference group], 130.0-159.9, 160.0-189.9, and ≥190.0 mg/dL) and all-cause and cause-specific mortality.ResultsDuring a median follow-up of 3.7 years, 57,391 and 23,241 deaths from all-cause and overall CVD were documented. We observed J-shaped associations between LDL-C and death from all-cause, overall CVD, coronary heart disease (CHD), and ischemic stroke, and an L-shaped association between LDL-C and hemorrhagic stroke (HS) mortality (P for non-linearity <0.001). Compared with the reference group (100.0-129.9 mg/dL), very low LDL-C levels (<70.0 mg/dL) were significantly associated with increased risk of overall CVD (hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 1.06-1.14) and HS mortality (HR: 1.37, 95% CI: 1.29-1.45). Very high LDL-C levels (≥190.0 mg/dL) were associated with increased risk of overall CVD (HR: 1.51, 95% CI: 1.40-1.62) and CHD mortality (HR: 2.08, 95% CI: 1.92-2.24). The stronger associations of very low LDL-C with risk of CVD mortality were observed in individuals with older age, low or normal body mass index, low or moderate 10-year atherosclerotic CVD risk, and those without diagnosed CVD or taking statins. Stronger associations between very high LDL-C levels and all-cause and CVD mortality were observed in younger people.ConclusionsPeople with very low LDL-C had a higher risk of all-cause, CVD, and HS mortality; those with very high LDL-C had a higher risk of all-cause, CVD, and CHD mortality. On the basis of our findings, comprehensive health assessment is needed to evaluate cardiovascular risk and implement appropriate lipid-lowering therapy for people with very low LDL-C.

Project description:BackgroundThe relationship between the total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio and all-cause and cardiovascular mortality has not been elucidated. Herein, we intend to probe the effect of the TC/HDL-C ratio on all-cause and cardiovascular mortality in the general population.MethodsFrom the 1999-2014 National Health and Nutrition Examination Surveys (NHANES), a total of 32,405 health participants aged ≥18 years were included. The TC/HDL-C levels were divided into five groups: Q1: <2.86, Q2: 2.86-3.46, Q3: 3.46-4.12, Q4: 4.12-5.07, Q5: >5.07. Multivariate Cox regression models were used to explore the relationship between the TC/HDL-C ratio and cardiovascular and all-cause mortality. Two-piecewise linear regression models and restricted cubic spline regression were used to explore nonlinear and irregularly shaped relationships. Kaplan-Meier survival curve and subgroup analyses were conducted.ResultsThe population comprised 15,675 men and 16,730 women with a mean age of 43 years. During a median follow-up of 98 months (8.1 years), 2,859 mortality cases were recorded. The TC/HDL-C ratio and all-cause mortality showed a nonlinear association after adjusting for confounding variables in the restricted cubic spline analysis. Hazard ratios (HRs) of all-cause mortality were particularly positively related to the level of TC/HDL-C ratio in the higher range >5.07 and in the lower range <2.86 (HR 1.26; 95% CI 1.10, 1.45; HR 1.18; 95% CI 1.00, 1.38, respectively), although the HRs of cardiovascular disease mortality showed no difference among the five groups. In the two-piecewise linear regression model, a TC/HDL-C ratio range of ≥4.22 was positively correlated with cardiovascular mortality (HR 1.13; 95% CI 1.02, 1.25). In the subgroup analysis, a nonlinear association between TC/HDL-C and all-cause mortality was found in those aged <65 years, men, and the no lipid drug treatment population.ConclusionA nonlinear association between the TC/HDL-C ratio and all-cause mortality was found, indicating that a too-low or too-high TC/HDL-C ratio might increase all-cause mortality. However, for cardiovascular mortality, it does not seem so. The cutoff value was 4.22. The individuals had higher cardiovascular mortality with a TC/HDL-C ratio >4.22.

Project description:ImportanceLimited evidence supports the association between low-density lipoprotein cholesterol (LDL-C) and mortality across different atherosclerotic cardiovascular disease (ASCVD) risk stratifications.ObjectiveTo explore the associations between LDL-C levels and mortality and to identify the optimal ranges of LDL-C with the lowest risk of mortality in populations with diverse ASCVD risk profiles.Design, setting, and participantsThe ChinaHEART project is a prospective cohort study that recruited residents aged 35 to 75 years from 31 provinces in mainland China between November 2014 and December 2022. Participants were categorized into low-risk, primary prevention, and secondary prevention cohorts on the basis of their medical history and ASCVD risk. Data analysis was performed from December 2022 to October 2023.Main outcomes and measuresThe primary end point was all-cause mortality, and secondary end points included cause-specific mortality. Mortality data were collected from the National Mortality Surveillance System and Vital Registration. The association between LDL-C levels and mortality was assessed by using Cox proportional hazard regression models with various adjusted variables.ResultsA total of 4 379 252 individuals were recruited, and 3 789 025 (2 271 699 women [60.0%]; mean [SD] age, 56.1 [10.0] years) were included in the current study. The median (IQR) LDL-C concentration was 93.1 (70.9-117.3) mg/dL overall at baseline. During a median (IQR) follow-up of 4.6 (3.1-5.8) years, 92 888 deaths were recorded, including 38 627 cardiovascular deaths. The association between LDL-C concentration and all-cause or cardiovascular disease (CVD) mortality was U-shaped in both the low-risk cohort (2 838 354 participants) and the primary prevention cohort (829 567 participants), whereas it was J-shaped in the secondary prevention cohort (121 104 participants). The LDL-C levels corresponding to the lowest CVD mortality were 117.8 mg/dL in the low-risk group, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort. The LDL-C concentration associated with the lowest all-cause mortality (90.9 mg/dL vs 117.0 mg/dL) and CVD mortality (87 mg/dL vs 114.6 mg/dL) were both lower in individuals with diabetes than in individuals without diabetes in the overall cohort.Conclusions and relevanceThis study found that the association between LDL-C and mortality varied among different ASCVD risk cohorts, suggesting that stricter lipid control targets may be needed for individuals with higher ASCVD risk and those with diabetes.

Project description:BackgroundThe non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as a novel composite lipid indicator for atherosclerosis. However, the association between NHHR and mortality in patients with diabetes or prediabetes remains unclear. Consequently, the objective of this study was to investigate the relationship between NHHR and both all-cause and cardiovascular mortality in US adults with diabetes or prediabetes.MethodsThis study included 12,578 adult participants with diabetes or prediabetes from the US National Health and Nutrition Examination Survey (1999-2018). Mortality outcomes were ascertained by linking to the National Death Index (NDI) record up to December 31, 2019. We employed a weighted multivariate Cox proportional hazards model and restricted cubic splines to assess the associations between NHHR and all-cause and cardiovascular mortality. A segmented Cox proportional hazards model was used for evaluating threshold effects. Furthermore, a competing risks analysis was performed to explore the relationship between NHHR and cardiovascular mortality.ResultsDuring a median follow-up period of 8.08 years, 2403 participants encountered all-cause mortality, with 662 of them specifically succumbing to cardiovascular mortality. The restricted cubic splines revealed a U-shaped association between NHHR and all-cause mortality, while an L-shaped association was observed for cardiovascular mortality. The analysis of threshold effects revealed that the inflection points for NHHR and all-cause and cardiovascular mortality were 2.72 and 2.83, respectively. Specifically, when the baseline NHHR was below the inflection points, a negative correlation was observed between NHHR and both all-cause mortality (HR: 0.76, 95% CI: 0.68-0.85) and cardiovascular mortality (HR: 0.70, 95% CI: 0.57-0.85). Conversely, when the baseline NHHR exceeded the inflection points, a positive correlation was observed between NHHR and both all-cause mortality (HR: 1.11, 95% CI: 1.06-1.16) and cardiovascular mortality (HR: 1.08, 95% CI: 1.00-1.16).ConclusionsAmong US adults with diabetes or prediabetes, a U-shaped association was observed between NHHR and all-cause mortality, whereas an L-shaped association was identified with cardiovascular mortality. The inflection points for all-cause and cardiovascular mortality were 2.72 and 2.83, respectively.

Project description:BackgroundBenefits of elevated high-density lipoprotein cholesterol (HDL-C) levels are challenged by reports demonstrating U-shaped relations between HDL-C levels and all-cause mortality; the association with cause-specific mortality is less studied.MethodsA total of 344 556 individuals (20-79 years, 52 % women) recruited from population-based health screening during 1985-2003 were followed until the end of 2018 for all-cause and cause-specific mortality by serum HDL-C level at inclusion of <30, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, 90-99 and >99 mg/dl (< 0.78, 0.78-1.01, 1.04-1.27, 1.30-1.53, 1.55-1.79, 1.81-2.04, 2.07-2.31, 2.33-2.56, >2.56 mmol/L). Hazard ratios (HRs) were adjusted for sex, age, calendar period, smoking, total cholesterol, triglycerides, systolic blood pressure, physical activity, educational length, body mass index and ill health.ResultsDuring a mean follow-up of 22 years, 69 505 individuals died. There were U-shaped associations between HDL-C levels and all-cause, cancer and non-cardiovascular disease/non-cancer mortality (non-CVD/non-cancer), whereas for CVD there was increased risk of death only at lower levels. With HDL-C stratum 50-59 mg/dl (1.30-1.53 mmol/L) as reference, HRs [95% confidence intervals (CIs)] for levels >99 mg/dl (>2.56 mmol/L) were 1.32 (1.21-1.43), 1.05 (0.89-1.24), 1.26 (1.09-1.46) and 1.68 (1.48-1.90) for all-cause, CVD, cancer and non-CVD/non-cancer mortality, respectively. For HDL-C levels <30 mg/dl (0.78 mmol/L), the corresponding HRs (95% CIs) were 1.30 (1.24-1.36), 1.55 (1.44-1.67), 1.14 (1.05-1.23) and 1.19 (1.10-1.29). The mortality from alcoholic liver disease, cancers of mouth-oesophagus-liver, chronic liver diseases, chronic obstructive pulmonary disease, accidents and diabetes increased distinctly with increasing HDL-C above the reference level. HDL-C levels lower than the reference level were mainly associated with increased mortality of ischaemic heart disease (IHD), other CVDs, stomach cancer and diabetes.ConclusionsHigher HDL-C levels were associated with increased mortality risk of several diseases which also have been associated with heavy drinking, and lower HDL-C levels were associated with increased mortality from IHD, other CVDs, gastric cancer and diabetes.

Project description:BackgroundObesity, often accompanied by dyslipidemia and increased cardiovascular risk, poses a significant threat to overall mortality. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has been identified as a valuable parameter for assessing dyslipidemia. The goal of the study was to elucidate the relationship between NHHR and mortality in obese populations.MethodsData for the study cohort were sourced from the National Health and Nutrition Examination Survey (1999-2018). The association between NHHR and mortality from all causes and cardiovascular disease was examined through multivariable Cox regression and restricted cubic splines (RCS). Segmented multivariable Cox regression and subgroup analyses were conducted when segmented effects were identified. The reliability of the results was confirmed through multiple sensitivity analyses.ResultsA total of 7,504 participants were included in the analysis. During a median follow-up of 119 months, 866 subjects died for all causes, of which 318 were related to cardiovascular diseases. A U-shaped association was found utilizing RCS analysis, with cardiovascular mortality and all-cause mortality exhibiting the lowest risk points at 3.409 and 3.369, respectively. The fully adjusted model revealed a negative relationship between the risk of cardiovascular mortality (HR = 0.68, 95% CI: 0.49-0.94) and all-cause mortality (HR = 0.82, 95% CI: 0.67-1.00) for per 1 mmol/L increase in NHHR levels below the cut-off value. On the other hand, above the cut-off point, NHHR was positively correlated with cardiovascular mortality (HR = 1.18, 95% CI: 1.02-1.36) and all-cause mortality (HR = 1.13, 95% CI: 1.01-1.28). The sensitivity results of this study were in accordance with earlier findings, and no significant interactions in NHHR levels were discovered across different subgroups.ConclusionsIn the obese adults, NHHR displayed a U-shaped relationship with cardiovascular and all-cause death. Monitoring and managing NHHR levels in obese population may help mitigate the risk of mortality.

Dataset Information

The U-shaped association of non-high-density lipoprotein cholesterol with all-cause and cardiovascular mortality in general adult population.

Background

Methods

Results

Conclusion

Publications

The U-shaped association of non-high-density lipoprotein cholesterol with all-cause and cardiovascular mortality in general adult population.

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