Association Of High-density Lipoprotein Cholesterol Research Articles

The association of cholesterol levels with memory and memory change over a 14-year period in a US national cohort.

The impact of cholesterol on late-life cognition remains controversial. We investigated the association of high-density lipoprotein cholesterol (HDL-C) and non-HDL-C with memory in a nationally representative cohort. Health and Retirement Study (HRS) participants (N=13,258) aged 50+ (mean age: 67.2 years) followed from 2006 to 2020 provided cholesterol measures every 4 years and cognitive assessments biennially. Linear mixed models predicted memory scores using both baseline and time-updated cholesterol values. Higher baseline HDL-C (mean: 53.9mg/dL) predicted better memory scores (β: 0.05, 95% confidence interval [CI]: 0.03 to 0.08), but not memory change. Baseline non-HDL-C (mean: 143mg/dL) predicted poorer memory scores (β: -0.01, 95% CI: -0.02 to 0.00), but not memory change. Time-updated HDL-C predicted better memory (β: 0.02, 95% CI: 0.00 to 0.04), but non-HDL-C showed no such associations. While higher peripheral HDL-C is linked to better memory, the small effect sizes and absence of associations of HDL-C and non-HD-CL with memory change suggests that peripheral cholesterol has a small effect on the variation of memory scores. Higher HDL-C levels predict better memory scores but not memory change across 14 years of follow-up.Baseline higher LDL-C levels predict poorer memory scores across time, but not memory change.The small effects and absence of consistent association between cholesterol levels and memory change suggest that cholesterol plays a minor role in cognitive decline.

Association of HDL cholesterol with all-cause and cardiovascular mortality in primary hypercholesterolemia

Recent reports have shown that subjects with high high-density lipoprotein cholesterol (HDLc) levels are paradoxically at increased risk for all-cause and cardiovascular mortality. The aim was to study the association of HDLc concentration with mortality in subjects with high cholesterol. We analyzed total mortality, cardiovascular mortality, and non-cardiovascular mortality in a cohort of 2992 subjects with primary hypercholesterolemia, who were followed for 10.2 years (range 1-25 years), with a total of 30,602 subject-years of follow-up. During follow-up, 168 subjects died, with 52 (13.7%), 105 (4.80%), and 11 (2.60%) in the low, normal, and high HDLc groups, respectively (p <0.001). The risk of death was 2.89 times higher (95% confidence interval (CI), 1.50-5.57, p<0.001) in subjects in the low HDLc group compared to those in the high HDLc group and 1.48 times higher (95% CI 0.80-2.76, p=0.214) in the normal HDLc group compared to the high HDLc group. However, HDLc concentration and HDLc groups based on HDLc concentration were not independently associated with mortality in Cox regression analysis. Cardiovascular and non-cardiovascular mortalities showed similar results. All types of mortality were lower in subjects with primary hypercholesterolemia and with high HDLc in univariate analysis. Elevated HDLc was not associated with total, cardiovascular, and non-cardiovascular mortality when adjusted for major cardiovascular risk factors.

Association of HDL cholesterol and cardiovascular disease in subjects with familial hypercholesterolemia

Association of HDL cholesterol and cardiovascular disease in subjects with familial hypercholesterolemia

Association of High-Density Lipoprotein Cholesterol with Sarcopenia in Chinese Community-Dwelling Middle-Aged and Older Adults: Evidence from 4-Year Longitudinal Study

Introduction: There is inconsistent evidence on the associations between high-density lipoprotein cholesterol (HDL-C) and risk of sarcopenia. The aim of the study was to determine the evidence existing between HDL-C and sarcopenia in Chinese middle-aged and older adults. Methods: We used a panel study design of the China Health and Retirement Longitudinal Study (CHARLS), with 7,415 participants (mean age 57.5 years) from 2011, 2013, and 2015. HDL-C was measured by colorimetric test of venous serum samples. Sarcopenia was defined as low muscle mass, plus low muscle strength, or low physical performance. Muscle mass was estimated by anthropometric measures. Muscle strength was measured by handgrip strength using dynamometer. Physical performance was measured by 5-time chair stand test, gait speed test, and short physical performance battery. Results: With 961 (13.0%) sarcopenia cases, each 1-unit increase (1 SD = 15.4 mg/dL) of HDL-C levels was associated with 42% increased odds of incident sarcopenia (OR = 1.42, 95% confidence interval [CI] = 1.28–1.58) at 4-year follow-up. Females with high HDL-C levels (HDL-C >60 mg/dL) had a higher risk of sarcopenia (OR = 2.49, 95% CI = 1.76–3.52). The restricted cubic spline curves showed a J-shaped association between HDL-C and risk of sarcopenia in females. HDL-C was negatively associated with muscle mass (β = −0.23, 95% CI = −0.27 to −0.20) and hand grip strength (β = −0.05, 95% CI = −0.19 to 0.09). Conclusion: High HDL-C levels were associated with higher risk of sarcopenia among middle-aged and older Chinese adults, and appropriate control of its high levels informs the management of sarcopenia.

Association of HDL-Cholesterol, hypertension and left ventricular hypertrophy in youths with overweight or obesity

To evaluate the relationship between HDL-Cholesterol (HDL-C), hypertension, and left ventricular hypertrophy (LVH) in a large sample of Caucasian youths with overweight/obesity (OW/OB). A cross-sectional multicenter study was performed in 1469 youths (age 6-16 years) with OW/OB observed in the period 2016-2020. An additional independent sample of 244 youths with an echocardiographic evaluation, observed in a single center was analyzed. The sample was divided in six quantiles (Q) of HDL-C: Q1: >56, Q2: ≤56>51, Q3: ≤51>45, Q4: ≤45>41, Q5: ≤41>39, Q6: <39mg/dL. The nadir of the relationship was identified in youths in the first quantile. Among HDL-Cholesterol quantiles the distribution of hypertension was non-linear with a percentage of 25.0%, 40.1%, 33.6%, 31.3%, 35.2% and 39.7% in the six quantiles, respectively. The percentage of LVH was 21.8%, 43.6%, 48.8%, 35.5%, 38.5% and 52.0% in the six quantiles, respectively. The highest odds [95%Cl] of hypertension were 2.05 (1.33-3.16) (P<0.01) in Q2, 1.67 (1.10-2.55) (P<0.05) in Q3 and 1.59 (1.05-2.41) (P<0.05) in Q6 vs Q1. The odds of LVH were 3.86 (1.15-10.24) (P<0.05) in Q2, 4.16 (1.58-10.91) (P<0.05) in Q3 and 3.60 (1.44-9.02) (P<0.05) in Q6 vs Q1, independently by centers, age, sex, prepubertal stage, and body mass index. Contrary to the common belief, the present study shows that high levels of HDL-C may be not considered a negative predictor of hypertension and LVH, two risk factors for future CV disease.

Association of high-density lipoprotein cholesterol with all-cause and cause-specific mortality in a Chinese population of 3.3 million adults: a prospective cohort study

High-density lipoprotein cholesterol (HDL-C) has been inversely associated with cardiovascular disease (CVD) risk, but recent evidence suggests that extremely high levels of HDL-C are paradoxically related to increased CVD incidence and mortality. This study aimed to comprehensively examine the associations of HDL-C with all-cause and cause-specific mortality in a Chinese population. The China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) project included 3,397,547 participants aged 35-75 years with a median follow-up of 3.9 years. Baseline HDL-C levels were measured, and mortality data was ascertained from the National Mortality Surveillance System and Vital Registration of Chinese Center for Disease Control and Prevention. This study found U-shaped associations of HDL-C with all-cause, cardiovascular and cancer mortality. When compared with the groups with the lowest risk, the adjusted hazard ratios (95% CIs) for HDL-C<30mg/dL was 1.23 (1.17-1.29), 1.33 (1.23-1.45) and 1.18 (1.09-1.28) for all-cause, CVD and cancer mortality, respectively. For HDL-C >90mg/dL, the corresponding HR (95% CIs) was 1.10 (1.05-1.15), 1.09 (1.01-1.18) and 1.11 (1.03-1.19). Similar U-shaped patterns were also found in associations of HDL-C with ischemic heart disease, ischemic stroke, and liver cancer. About 3.25% of all-cause mortality could be attributed to abnormal levels of HDL-C. The major contributor to mortality was ischemic heart disease (16.06 deaths per 100,000 persons, 95% UI: 10.30-22.67) for HDL-C<40mg/dL and esophageal cancer (2.29 deaths per 100,000 persons, 95% UI: 0.57-4.77) for HDL-C >70mg/dL. Both low and high HDL-C were associated with increased mortality risk. We recommended 50-79mg/dL as the optimal range of HDL-C among Chinese adults. Individuals with dyslipidemia might benefit from proper management of both low and high HDL-C. The CAMS Innovation Fund for Medical Science (2021-1-I2M-011), the National High Level Hospital Clinical Research Funding (2022-GSP-GG-4), the Ministry of Finance of China and National Health Commission of China, and the 111 Project from the Ministry of Education of China (B16005), the Program for Guangdong Introducing Innovative and Enterpreneurial Teams (2019ZT08Y481), Sanming Project of Medicine in Shenzhen (SZSM201811096), the Young Talent Program of the Academician Fund, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen (YS-2022-006) and Guangdong Basic and Applied Basic Research Foundation (2023A1515010076 & 2021A1515220173).

Effect of high density lipoprotein cholesterol (HDL-C) on renal outcome in patients with nephrotic syndrome complicated with steroid-induced diabetes mellitus(SIDM)

ObjectiveWe aimed to investigate the renal prognosis of patients with idiopathic nephrotic syndrome (INS) complicated with steroid-induced diabetes mellitus (SIDM), the association of high-density lipoprotein cholesterol (HDL-C) before glucocorticoid treatment with renal prognosis, and the risk for persistent diabetes among patients with INS who had withdrawn from steroid therapy.Materials and methodsWe retrospectively analyzed 239 patients with INS complicated with SIDM at the National Clinical Research Center of Kidney Diseases, Jinling Hospital, from January 2008 to December 2019. The primary endpoint was the composite renal outcome defined as the development of end-stage renal disease (ESRD) or a 50% decrease in estimated glomerular filtration rate (eGFR) for more than 24 months after glucocorticoid withdrawal. The secondary endpoint was persistent diabetes, defined as fulfilling the criteria for diagnosing diabetes or using antidiabetic medications for at least 24 months after glucocorticoid withdrawal.ResultsAfter glucocorticoid withdrawal for over 24 months, 35 (14.6%) patients reached the composite renal endpoint: end-stage renal disease (n = 14) or a 50% decrease in eGFR (n = 21). Before glucocorticoid therapy, a level of HDL-C greater than 1.45 mmol/L worsened renal survival in patients with INS complicated with SIDM. The log10 the level of HDL-C before glucocorticoid treatment was an independent risk factor for the renal outcome. A prediction model was generated: Hazard ratio (renal outcome) = 0.94 * hypertension before glucocorticoid therapy + 2.29 * log10 level of HDL-C before glucocorticoid treatment + 0.90 * the grade of interstitial tubule injury (AUROC, 0.75; 95% CI, 0.63 to 0.87; P < 0.01). Meanwhile, a level of fasting plasma glucose (FPG) before glucocorticoid treatment greater than 5.2 mmol/L enhanced the likelihood of persistent diabetes for at least 24 months after glucocorticoid withdrawal.ConclusionsIncreased level of HDL-C before glucocorticoid therapy was independently associated with a higher risk for renal outcome and thus may be useful in the renal prognosis of patients with INS complicated with SIDM.

Association of High-Density Lipoprotein Cholesterol, Renal Function, and Metabolic Syndrome: An Assessment of the 2013–2018 National Health and Nutrition Examination Surveys

Previous findings assessing the relationship between high-density lipoprotein cholesterol (HDL-c) and kidney function have demonstrated contradictory results including positive, negative, and U-shaped relationships. Many prior studies in this area have been conducted in healthy populations, but few have considered the influence of metabolic health status. In the present study, a cross-sectional analysis was conducted using complex survey sample weighting in the assessment of 6455 subjects from the 2013–2018 National Health and Nutrition Examination Surveys (NHANES), representative of 94,993,502 United States citizens. Subjects were classified as metabolically healthy or unhealthy and linear regression analyses were performed to evaluate the influence of HDL-c on estimated glomerular filtration rate (eGFR). HDL-c was found to be negatively associated with eGFR in the metabolically healthy, unhealthy, and combined groups (B = −0.16, p &lt; 0.0001, B = −0.21, p &lt; 0.0001, and B = −0.05, p = 0.0211, respectively). This relationship persisted after adjustment for confounding variables (B = −0.24, p &lt; 0.0001, B = −0.17, p &lt; 0.001, and B = −0.18, p &lt; 0.0001, respectively). The relationship between HDL-c and eGFR was found to be a negative linear association, rather than a U-shaped association, and it persisted in all models tested, despite statistical adjustment for confounding variables. After controlling the samples for outliers, the negative relationship between HDL-c and eGFR was attenuated in the healthy and total groups but remained significant in the MetS group, indicating a stronger relationship between HDL-c and eGFR in those with poorer health.

Association of high-density lipoprotein cholesterol and periodontitis severity in Chinese elderly: a cross-sectional study.

Periodontitis is a local inflammatory disease of high prevalence worldwide. Increasing evidence has shown its association with cardiovascular diseases. While high-density lipoprotein is an important protective factor in preventing cardiovascular diseases, this study aims to examine whether high-density lipoprotein cholesterol (HDL-C) level is associated with different status of periodontitis. A total of 874 Chinese retirees (≥ 60years of age) with different statuses of periodontitis were enrolled. Periodontal clinical data were collected to define periodontal disease severity (no, mild-moderate, severe). Peripheral blood was collected for serum lipid profile analysis. Linear and logistic regression analysis with adjustment for potential confounders (gender, age, BMI, alcohol intake, exercise frequency, smoking habits) were used to determine the association of periodontitis with HDL-C. After adjustments for confounders, linear regression analyses revealed a significant relationship between the decreased HDL-C and periodontitis severity (p < 0.05). Although the multivariable-adjusted ORs of decreased HDL-C were not statistically significant, logistic regression analyses showed Chinese elderly with severe periodontitis had higher odds of exhibiting clinically abnormal HDL-C levels than those without periodontitis. The elderly population with periodontitis showed HDL-C levels significantly lower than those without periodontitis. The severity of periodontitis was positively correlated with serum HDL-C levels. Periodontitis reduces HDL-C level in the elderly population, indicating that oral health should be paid attention to in the prevention and treatment of dyslipidemia.

Association of high-density lipoprotein cholesterol with risk of cardiovascular disease mortality

Objective: To analyze the association between high density lipoprotein cholesterol (HDL-C) and the risk of cardiovascular disease mortality. Methods: A total of 71 618 residents aged over 18 years with complete baseline data, who were filed on the health information big data platform of Yinzhou district, Ningbo city, Zhejiang Province from 2009 to 2014, were selected as the research population. The research population were divided into four groups according to the level of HDL-C: low-level group (HDL-C<1.0 mmol/L), intermediate-level group (1.0 mmol/L≤HDL-C<1.5 mmol/L), medium-high-level group (1.5 mmol/L≤HDL-C<2.0 mmol/L) and high-level group (HDL-C≥2.0 mmol/L). Cox proportional hazard model was used to calculate the risk ratio of cardiovascular diseases mortality in different groups. Results: The study population was followed up for a total of 427 989.4 person-years, follow-up time of (5.98±1.04)years. During the follow-up period, there were 799 deaths due to cardiovascular diseases. After adjusting for confounding factors, compared with the medium-high-level group as the reference group, the HR (95%CI) for cardiovascular diseases mortality was 1.43 (1.13-1.82) in the low-level group and 1.22 (1.02-1.46) in the high-level group. Conclusion: The low level of HDL-C (<1.5 mmol/L) is associated with a higher risk of cardiovascular disease deaths. The level of HDL-C can be used as a biological indicator to monitor the development of cardiovascular diseases and guide treatment.

Value of high-density lipoprotein cholesterol in evaluating the severity and prognosis of hepatitis B virus-associated acute-on-chronic liver failure

Objective To investigate the association of high-density lipoprotein cholesterol (HDL-C) with the prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) and its predictive value. Methods The patients with liver disease who were admitted to Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, from January 2015 to January 2019 were enrolled, and according to the stage of disease progression, they were divided into HBV-ACLF group with 42 patients, liver cirrhosis group with 30 patients, and chronic hepatitis group with 25 patients. A total of 24 healthy individuals were enrolled as healthy control group. General clinical data were collected, including sex, age, prothrombin time (PT), albumin (Alb), total bilirubin (TBil), serum creatinine, blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), HDL-C, low-density lipoprotein cholesterol (LDL-C), and Model for End-Stage Liver Disease (MELD) score. The HBV-ACLF group was further divided into improvement group with 17 patients and non-improvement group with 25 patients, and the patients were followed up for 3 months. The Mann-Whitney U test was used for comparison of non-normally distributed continuous variables between two groups; the Kruskal-Wallis H test was used for comparison between multiple groups, and the Wilcoxon rank-sum test was used for comparison within each group. A binary logistic regression analysis was used to investigate independent risk factors for prognosis, and the receiver operating characteristic (ROC) curve was used to evaluate the accuracy of the variables in prediction. Results There were significant differences in PT, Alb, BUN, TBil, TC, TG, HDL-C, LDL-C, and MELD scores between the liver cirrhosis group, the HBV-ACLF group, the chronic hepatitis group, and the healthy control group (χ2=75.134, 44.638, 10.253, 80.357, 55.067, 19.858, 68.174, 52.492, and 64.359, all P Conclusion HDL-C is an independent risk factor for the prognosis of patients with HBV-ACLF and has a good value in predicting the prognosis of HBV-ACLF.

Phenotypes of high-density lipoprotein cholesterol and their relationship with glycemic status in type 2 diabetic patients

Background: There are varying reports on the association of high-density lipoprotein cholesterol (HDL-C) phenotypes and glycemia in type 2 diabetes mellitus (T2D) patients. Such information is lacking in Nigerian data. Aim: The aim of this study was to determine the relationship between HDL-C phenotypes and glycemic control in T2D patients. Materials and Methods: Clinical and laboratory data were collected from consenting T2D patients. Information was managed and analyzed with appropriate software. Results: Four hundred T2D patients consisting of 235 and 165 persons with and without poor glycemic control, respectively, were recruited for this study. There was a significant negative correlation between glycosylated hemoglobin (HbA1c) and the HDL2-C phenotype (rs = −0.12, P = 0.01). The correlation between HbA1c and the HDL3-C phenotype was not statistically significant (rs = −0.06, P = 0.21). Conclusion: The HDL2 phenotype has a stronger correlation with glycemic status than the HDL3 phenotype in T2D patients.

A Non-Linear Association of High-Density Lipoprotein Cholesterol with All-Cause and Cause-Specific Mortality in Diabetic Patients.

BackgroundThe association between high-density lipoprotein cholesterol (HDL-C) and the risk of death among people with diabetes remains to be verified.MethodsThis was a nationwide, population-based cohort study in United States. A total of 6549 diabetes patients were included from the National Health and Nutrition Examination Surveys (NHANES). HDL-C concentration was divided into quintiles, and the lowest risk group (Q4: 1.32 to 1.53 mmol/L) was used as reference. Multivariate Cox proportional hazards models and restrictive cubic curves were performed to estimate hazard ratios (HRs) with 95% confidence interval (CI) for all-cause and cause-specific mortality.ResultsDuring a median follow-up of 82.36 ± 50.11 months, 1546 (23.61%) cases of all-cause, 389 (5.94%) cardiovascular and 262 (4.00%) cancer mortality have occurred, respectively. After adjusting for potential covariates, a U-shaped association was found between HDL-C and all-cause mortality (minimum mortality risk at 1.37 mmol/L); the risk for all-cause mortality was significantly higher in the groups with HDL-C concentration <0.96 mmol/L (HR: 1.30; 95% CI: 1.09, 1.56; P=0.0046) and with HDL-C concentration ≥1.55 mmol/L (HR: 1.20; 95% CI: 1.00, 1.44; P=0.0481) than participants with HDL-C concentrations ranging from 1.32 to 1.53mmol/L. Nonlinear associations of HDL-C levels with both cardiovascular and cancer mortality were also observed.ConclusionA non-linear association was observed association of HDL-C with all-cause, cardiovascular and cancer mortality among diabetic patients.

Association of High-Density Lipoprotein Cholesterol With GFR Decline in a General Nondiabetic Population

IntroductionAlthough lower high-density lipoprotein cholesterol (HDL-C) levels are considered a risk factor for cardiovascular disease (CVD), experimental evidence suggest that aging, inflammation, and oxidative stress may remodel HDL-C, leading to dysfunctional HDL-C. Population studies on HDL-C and loss of the glomerular filtration rate (GFR) reported inconsistent results, but they used inaccurate estimates of the GFR and may have been confounded by comorbidity.MethodsWe investigated the association of HDL-C levels with risk of GFR loss in a general population cohort; the participants were aged 50–62 years and did not have diabetes, CVD, or chronic kidney disease (CKD) at baseline. The GFR was measured using iohexol-clearance at baseline (n=1627) and at the follow-up (n=1324) after a median of 5.6 years. We also investigated any possible effect modification by low-grade inflammation, physical activity, and sex.ResultsHigher HDL-C levels were associated with steeper GFR decline rates and increased risk of rapid GFR decline (>3 ml/min per 1.73 m2 per year) in multivariable adjusted linear mixed models and logistic regression (–0.64 ml/min per 1.73 m2 per year [95% CI –0.99, –0.29; P < 0.001] and odds ratio 2.7 [95% CI 1.4, 5.2; P < 0.001] per doubling in HDL-C). Effect modifications indicated a stronger association between high HDL-C and GFR loss in physically inactive persons, those with low-grade inflammation, and men.ConclusionHigher HDL-C levels were independently associated with accelerated GFR loss in a general middle-aged nondiabetic population.

Positive association of high-density lipoprotein cholesterol with lumbar and femoral neck bone mineral density in postmenopausal women

Experimental studies suggest that lipids affect bone metabolism. We aimed to elucidate whether lipid levels are associated with bone mineral density (BMD) in a cohort of postmenopausal women. A cross-sectional study of participants in the Chronic Ailment Reduction after MENopause (CARMEN) cohort. Women underwent assessment of clinical and analytical parameters, including fasting lipid levels. BMD was assessed at both lumbar spine and hip. Homogeneity in the cohort was optimized by filtering out a series of confounding variables with a known impact on bone. Association of BMD at lumbar spine and femoral neck with lipid levels. A total of 667 of the 1304 screened women were analyzed. A strong correlation was revealed between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in univariate analysis. Multivariate analysis detected a significant positive association of HDL-C with BMD at both spine (p = 0.007) and femoral neck (p = 0.013). Other independent predictors of spine BMD were years since menopause (ysm, negatively associated), and body mass index (BMI) and estradiol, both positively associated with BMD. The other independent variables in the femoral neck were ysm and glucose (negatively associated) and BMI, estradiol, and phosphate, all positively associated with BMD. Levels of HDL-C, but not TC, LDL-C or triglycerides, were positively associated with BMD at both the lumbar spine and femoral neck in a homogeneous cohort of postmenopausal women.

Association of High-Density Lipoprotein Cholesterol With Sex Steroid Treatment in Transgender and Gender-Diverse Youth

This cohort study analyzes the association of sex steroids with cholesterol in different sex-chromosome contexts.

Associations of HDL metrics with coronary artery calcium score and density among women traversing menopause

The cardioprotective association of high-density lipoprotein cholesterol (HDL-C) may vary by menopause stage or estradiol level. We tested whether associations of comprehensive HDL metrics (HDL subclasses, phospholipid and triglyceride content, and HDL cholesterol efflux capacity [HDL-CEC]) with coronary artery calcium (CAC) score and density vary by menopause stage or estradiol level in women transitioning through menopause. Participants (N = 294; mean age [SD]: 51.3 [2.9]) had data on HDL metrics and CAC measures at one or two time points during the menopause transition. Generalized estimating equations were used for analyses. Effect modifications by menopause stage or estradiol level were tested in multivariable models. In adjusted models, menopause stage modified the associations of specific HDL metrics with CAC measures. Higher small HDL particles (HDL-P) concentrations (p-interaction = 0.008) and smaller HDL size (p-interaction = 0.02) were associated with greater odds of CAC presence in late perimenopause than in pre/early perimenopause stage. Women in the highest estradiol tertile, but not the lower tertiles, showed a protective association of small HDL-P with CAC presence (p-interaction = 0.007). Lower large HDL-P concentrations (p-interaction = 0.03) and smaller HDL size (p-interaction = 0.03) were associated with lower CAC density in late perimenopause than in postmenopause stage. Associations of HDL phospholipid and triglyceride content and HDL-CEC with CAC measures did not vary by menopause stage or estradiol level. We concluded that HDL subclasses may impact the likelihood of CAC presence and the stability of coronary plaque differently over the menopause transition. Endogenous estradiol levels may contribute to this observation.

High-density lipoprotein cholesterol and arterial calcification in midlife women: the contribution of estradiol and C-reactive protein.

Studies suggest a reversal in the protective association of high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease in women traversing menopause. Decreasing estrogen levels during the transition, as well as inflammation, may explain this reversal. We tested whether either estradiol or C-reactive protein (CRP) concentrations modified the association of HDL-C with aortic (AC) or coronary artery calcification (CAC). A total of 478 participants between ages 46 to 59 from the Study of Women's Health Across the Nation Heart baseline visit were included. AC and CAC presence were defined as Agatston score of 100 or higher and 10 or higher, respectively. Logistic regression was used for analysis. A total of 112 (23.53%) participants had AC 100 or higher and 104 (21.76%) had CAC 10 or higher. In unadjusted models, a 1-mg/dL higher in HDL-C was associated with 3% lower odds of AC (95% CI: 0.95-0.99) and 4% lower odds of CAC (95% CI: 0.95-0.98). In adjusted models, a significant interaction between HDL-C and estradiol with respect to AC but not CAC was detected, such that higher HDL-C level was protective at the highest estradiol quartile (odds ratio: 0.91, 95% CI: 0.84-0.99 per 1 mg/dL higher HDL-C, P = 0.03) but tended to associate with greater risk at the lowest quartile (odds ratio: 1.04, 95% CI: 0.98-1.10 per 1 mg/dL higher HDL-C, P = 0.16). CRP did not modify any association. The protective cardiovascular association of higher HDL-C levels on AC was modified by estradiol but not CRP concentrations. The pathways through which estradiol might influence this association should be further investigated.

U-Shaped Association of High-Density Lipoprotein Cholesterol with All-Cause and Cardiovascular Mortality in Hypertensive Population.

PurposeWhether 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.MethodsIn 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.ResultsDuring 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 all-cause 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).ConclusionBoth 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.

The U Shaped Relationship Between High-Density Lipoprotein Cholesterol and All-Cause or Cause-Specific Mortality in Adult Population.

PurposeThe associations of high-density lipoprotein cholesterol (HDL-C) with mortality are still unclear. We explored the associations of HDL-C with all-cause and cause-specific mortality in an adult population.MethodsDeaths were classified into all-cause, cardiovascular, and cancer mortality. Survival curve, multivariate Cox regression, and subgroup analyses were conducted, and hazard ratio (HR) and 95% confidence interval (CI) were performed. We fitted Cox regression models for all-cause, cardiovascular, and cancer mortality to evaluate their associations with categories of HDL-C (≤30, 31–40, 41–50, 51–60 [reference], 61–70, >70 mg/dL).ResultsA total of 42,145 (20,415 (48.44%) males, mean age 47.12±19.40 years) subjects were enrolled. At an average follow-up of 97.52±54.03 months, all-cause, cardiovascular, and cancer mortality numbers were 5,061 (12.01), 1,081 (2.56%), and 1,061 (2.52%), respectively. When compared with the reference group (HDL-C: 51–60 mg/dL), a U-shaped association was apparent for all-cause mortality, with elevated risk in participants with the lowest (≤30 mg/dL) (HR=1.33; 95% CI=1.14– 1.56) and highest (>70 mg/dL) (HR=1.14; 95% CI=1.02–1.27) HDL-C concentration. Associations for cardiovascular and cancer mortality were non-linear. An elevated risk for cancer mortality was observed in those with the highest HDL-C concentration (HR=1.06; 95% CI–0.84–1.34) compared with the reference group, although it was not statistically significant. The effect of HDL-C on mortality was adjusted by some traditional risk factors including age, gender, race, or comorbidities.ConclusionA U-shaped association was observed between HDL-C and all-cause mortality among an adult population.