Association between serum high-density lipoprotein cholesterol and lung function in adults: three cross-sectional studies from US and Korea National Health and Nutrition Examination Survey

Prevalence of Elevated Alanine Aminotransferase Among US Adolescents and Associated Factors: NHANES 1999–2004

Urinary acrolein metabolites, systemic inflammation, and blood lipids: Results from the National Health and Nutrition Examination Survey

Knowledge Gap Regarding Low Density Lipoprotein-Cholesterol Levels in Koreans

Case Presentation: Mr A is a healthy 38-year-old black male who comes to the clinic as a self-referral after a blood pressure check during “Health Day” at his job. Mr A is concerned because “high blood pressure” runs in his family. He reveals that his 58-year-old mother recently suffered a mild stroke and also takes water pills to reduce swelling in her legs. He denies any other health problems, is a non-smoker, and takes no medications. On physical examination, his supine blood pressure is 165/85, his heart rate is 74 bpm, and his weight is 72 kg. An ECG shows normal sinus rhythm at 76 bpm and evidence of left ventricular hypertrophy. A fasting lipid profile shows a total cholesterol level of 196 mg/dL, a low-density lipoprotein cholesterol (LDL-C) level of 120 mg/dL, a high-density lipoprotein cholesterol (HDL-C) level of 50 mg/dL, a triglyceride level of 130 mg/dL, and C-reactive protein level of 3.5 mg/L. What clinical strategy would be most appropriate for Mr A? What is the available scientific evidence to support your choice(s)? Despite advances in the diagnosis and treatment of cardiovascular disease (CVD), morbidity and mortality from CVD is higher among black Americans than among white, Hispanic, and Asian Americans.1 Although black Americans are often considered to have less obstructive coronary heart disease than age-matched whites,2,3 the prevalence of traditional risk factors for CVD such as hypertension, diabetes mellitus, smoking, and obesity disproportionately affects black Americans. However, the relative importance of these risk factors and others, such as left ventricular hypertrophy, dyslipidemia, and novel risk determinants such as C-reactive protein and lipoprotein (a), on morbidity and mortality is unclear. At the population level, research efforts have focused primarily on the components of the Framingham Cardiovascular Risk Equation that were developed in a predominantly white cohort. …

A long-standing association exists between elevated triglyceride levels and cardiovascular disease* (CVD).1,2 However, the extent to which triglycerides directly promote CVD or represent a biomarker of risk has been debated for 3 decades.3 To this end, 2 National Institutes of Health consensus conferences evaluated the evidentiary role of triglycerides in cardiovascular risk assessment and provided therapeutic recommendations for hypertriglyceridemic states.4,5 Since 1993, additional insights have been made vis-a-vis the atherogenicity of triglyceride-rich lipoproteins (TRLs; ie, chylomicrons and very low-density lipoproteins), genetic and metabolic regulators of triglyceride metabolism, and classification and treatment of hypertriglyceridemia. It is especially disconcerting that in the United States, mean triglyceride levels have risen since 1976, in concert with the growing epidemic of obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM).6,7 In contrast, mean low-density lipoprotein cholesterol (LDL-C) levels have receded.7 Therefore, the purpose of this scientific statement is to update clinicians on the increasingly crucial role of triglycerides in the evaluation and management of CVD risk and highlight approaches aimed at minimizing the adverse public health–related consequences associated with hypertriglyceridemic states. This statement will complement recent American Heart Association scientific statements on childhood and adolescent obesity8 and dietary sugar intake9 by emphasizing effective lifestyle strategies designed to lower triglyceride levels and improve overall cardiometabolic health. It is not intended to serve as a specific guideline but will be of value to the Adult Treatment Panel IV (ATP IV) of the National Cholesterol Education Program, from which evidence-based guidelines will ensue. Topics to be addressed include epidemiology and CVD risk, ethnic and racial differences, metabolic determinants, genetic and family determinants, risk factor correlates, and effects related to nutrition, physical activity, and lipid medications. In the United States, the National Health and …

Optimal high-density lipoprotein cholesterol cutoff for predicting cardiovascular disease: Comparison of the Korean and US National Health and Nutrition Examination Surveys

Risk Factors for Cardiovascular Disease in Children Infected with Human Immunodeficiency Virus-1

Low levels of high-density lipoprotein cholesterol (HDL-C) are commonly seen in patients with type 2 diabetes mellitus (T2DM). However, it is unclear whether there is an independent or causal link between HDL-C levels and T2DM. This study aims to address this gap by using the The National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analysis. Data from the NHANES survey (2007-2018) with 9,420 participants were analyzed using specialized software. Logistic regression models and restricted cubic splines (RCS) were used to assess the relationship between HDL-C and T2DM incidence, while considering covariates. Genetic variants associated with HDL-C and T2DM were obtained from genome-wide association studies (GWAS), and Mendelian randomization (MR) was used to evaluate the causal relationship between HDL-C and T2DM. Various tests were conducted to assess pleiotropy and outliers. In the NHANES study, all groups, except the lowest quartile (Q1: 0.28-1.09 mmol/L], showed a significant association between HDL-C levels and reduced T2DM risk (all P < 0.001). After adjusting for covariates, the Q2 [odds ratio (OR) = 0.67, 95% confidence interval (CI): (0.57, 0.79)], Q3 [OR = 0.51, 95% CI: (0.40, 0.65)], and Q4 [OR = 0.29, 95% CI: (0.23, 0.36)] groups exhibited average reductions in T2DM risk of 23%, 49%, and 71%, respectively. In the sensitivity analysis incorporating other lipid levels, the Q4 group still demonstrates a 57% reduction in the risk of T2DM. The impact of HDL-C levels on T2DM varied with age (P for interaction = 0.006). RCS analysis showed a nonlinear decreasing trend in T2DM risk with increasing HDL-C levels (P = 0.003). In the MR analysis, HDL-C levels were also associated with reduced T2DM risk (OR = 0.69, 95% CI = 0.52-0.82; P = 1.41 × 10-13), and there was no evidence of pleiotropy or outliers. This study provides evidence supporting a causal relationship between higher HDL-C levels and reduced T2DM risk. Further research is needed to explore interventions targeting HDL-C levels for reducing T2DM risk.

BackgroundDyslipidemia, typically recognized as high serum triglyceride, high low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) levels, are associated with nonalcoholic fatty liver disease (NAFLD). However, low LDL-C levels could result from defects in lipoprotein metabolism or impaired liver synthetic function, and may serve as ab initio markers for unrecognized liver diseases. Whether such relationships exist in the general population has not been investigated. We hypothesized that despite common conception that low LDL-C is desirable, it might be associated with elevated liver enzymes due to metabolic liver diseases.Methods and FindingsWe examined the associations between alanine aminotransferase (ALT), aspartate aminotransferase (AST) and major components of serum lipid profiles in a nationally representative sample of 23,073 individuals, who had no chronic viral hepatitis and were not taking lipid-lowering medications, from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. ALT and AST exhibited non-linear U-shaped associations with LDL-C and HDL-C, but not with triglyceride. After adjusting for potential confounders, individuals with LDL-C less than 40 and 41–70 mg/dL were associated with 4.2 (95% CI 1.5–11.7, p = 0.007) and 1.6 (95% CI 1.1–2.5, p = 0.03) times higher odds of abnormal liver enzymes respectively, when compared with those with LDL-C values 71–100 mg/dL (reference group). Surprisingly, those with HDL-C levels above 100 mg/dL was associated with 3.2 (95% CI 2.1–5.0, p<0.001) times higher odds of abnormal liver enzymes, compared with HDL-C values of 61–80 mg/dL.ConclusionsBoth low LDL-C and high HDL-C, often viewed as desirable, were associated with significantly higher odds of elevated transaminases in the general U.S. adult population. Our findings underscore an underestimated biological link between lipoprotein metabolism and liver diseases, and raise a potential need for liver evaluation among over 10 million people with particularly low LDL-C or high HDL-C in the United States.

BackgroundPrevious studies have shown that high-density lipoprotein cholesterol (HDL-C) levels are positively associated with cognitive function across a range of concentrations. However, recent studies have suggested that very high HDL-C levels may lead to poorer outcomes. Therefore, we aimed to investigate the relationship between different concentrations of HDL-C and cognitive impairment risk.MethodsWe collected data from 3632 participants aged over 60 years from the U.S. National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014 to assess the relationship between HDL-C and cognitive function. Cognitive function was evaluated with the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test, the animal fluency test (AFT), and the digit symbol substitution test (DSST). We used restricted cubic spline models and logistic regression to examine the association between HDL-C and cognitive function.ResultsA U-shaped was observed between HDL-C and cognitive outcomes, individuals with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (≥ 2.50 mmol/L) were associated with increased risk of cognitive impairment (OR = 2.19; 95% CI, 1.12–4.28) compared with those with HDL-C levels in the range of 1.50 to 1.99 mmol/L in older adults after adjustment for confounding factors. Interaction test demonstrated that relationship between very high HDL-C and the risk of cognitive impairment was not changed in different sex and race group (P for interaction > 0.05).ConclusionsVery high HDL-C levels were associated with an increased risk of cognitive impairment. HDL-C may not be a protective factor for maintaining brain health in older adults at very high levels.

Exercise Mitigates the Association of Abdominal Obesity with High-density Lipoprotein Cholesterol in Premenopausal Women: Results from the third National Health and Nutrition Examination Survey

Although sarcopenia and insulin resistance are closely related, there is limited evidence regarding how they interact to influence mortality across different population groups. The purpose of this study was to examine the relationship between skeletal muscle mass and insulin resistance and its impact on mortality and cardiovascular disease risk using large-scale national data from Korea and the United States. We analysed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 and 2011-2018 and the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011, with mortality follow-up through to 2019. Cox regression models were used to assess the effects of muscle mass (appendicular skeletal mass index, ASMI) and insulin resistance on all-cause and major adverse cardiovascular and cerebrovascular events (MACCE)-related mortality. Mediation analysis was performed to examine direct and indirect effects. The study included 8036 participants from NHANES and 14 449 from KNHANES. The sarcopenia group demonstrated a lower homeostasis model assessment for insulin resistance and better metabolic indices than the normal group despite having a higher mortality rate. Insulin resistance positively correlated with muscle mass (r = 0.203, p < 0.001 in the NHANES; r = 0.143, p < 0.001 in the KNHANES), and both insulin resistance and sarcopenia were identified as independent risk factors for all-cause and MACCE-related mortality. When the participants were categorized into four groups based on the presence or absence of insulin resistance and sarcopenia, those with both conditions exhibited the highest risk of all-cause mortality (hazard ratio [HR]: 2.30, 95% confidence interval [CI]: 1.72-3.08 in the NHANES; HR: 2.60, 95% CI: 2.14-3.16 in the KNHANES) and MACCE-related mortality among the groups (HR: 3.18, 95% CI: 1.99-5.08 in the NHANES; HR: 2.47, 95% CI: 1.66-3.69 in the KNHANES). Mediation analysis revealed that low muscle mass was associated with decreased insulin resistance but directly increased both all-cause mortality and MACCE-related mortality (NHANES: total natural direct effects [TNDE], HR: 2.08, 95% CI: 1.57-2.76; KNHANES: TNDE, HR: 1.69, 95% CI: 1.28-2.23). This study found that low ASMI was inversely associated with insulin resistance and positively associated with mortality risk in both cohorts. These findings, consistent across two large national studies, highlight the complex relationships between muscle mass, insulin sensitivity and mortality. Further studies are needed to assess the underlying mechanisms and clinical implications of these associations. Clinicaltrials.gov ID: NCT05616013.

Background: Decreasing total cholesterol (TC) and increasing high-density lipoprotein cholesterol (HDL-C) levels have been observed over the past several decades in the US population. It is not clear if the obesity epidemic has mitigated these favorable changes. Hypothesis: Associations between birth cohort and TC and HDL-C levels are partially attenuated by body mass index (BMI). Methods: We examined differences in TC and HDL-C levels across US birth cohorts born between 1930-1998 from the National Health and Nutrition Examination Surveys (NHANES) exam cycles 1999-2016, and the impact of body mass index (BMI) on these differences. A series of 10-year birth cohorts were constructed (1930-1998). Survey-weighted multivariable-adjusted linear regression models were used. Results: Among 40,273 participants, 50% were women and 22% non-Hispanic Blacks. After adjustment for age, sex, race, and lipid-lowering medication use, (and age 2 for the TC model), population mean TC decreased by 5.15 mg/dL and mean HDL-C increased by 1.34 mg/dL for each more recent birth cohort (all P&lt;.001) ( Table ). There was an interaction between age and birth cohort for TC, with greater decreases with aging; for example, the mean of TC was 4.14, 6.48, and 8.83 mmHg lower for each more recent birth cohorts at the age of 30, 50, and 70, respectively. BMI was positively associated with TC and negatively associated with HDL-C. However, BMI only slightly influenced the association of birth cohort with TC (2%), but it strongly influenced the birth cohort effect on HDL-C (31%). Conclusion: More recent birth cohorts had lower TC levels and higher HDL-C levels than older birth cohorts in the US. These favorable birth cohort effects were partially compromised by BMI. Research into the environmental and behavioral differences between 20 th century US birth cohorts is needed to support future efforts to reduce the prevalence of dyslipidemia.

BackgroundPrevious studies have shown that extremely high levels of high-density lipoprotein (HDL) cholesterol are paradoxically associated with adverse outcomes in certain clinical settings. We aimed to test the hypothesis that extremely high levels of HDL cholesterol are associated with increased all-cause and cause-specific mortality in the general population.MethodsWe included 51,235 individuals from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2018 with a median follow-up of 9.3 years. Baseline HDL cholesterol levels were measured, and mortality data were ascertained from National Death Index (NDI) records through December 31, 2019. Weighted Cox proportional hazards regression, restricted cubic spline curves, and cumulative incidence analyses were performed.ResultsA U-shaped association was observed between HDL cholesterol levels and all-cause, cardiovascular and non-cardiovascular mortality in the general population. Compared with individuals with HDL cholesterol levels between 50 and 59 mg/dL, the adjusted hazard ratios (95% CIs) for those with extremely high HDL cholesterol levels (≥ 80 mg/dL) were 1.24 (1.08–1.43), 1.18 (1.03–1.36) and 1.27 (1.09–1.49) for all-cause, cardiovascular and non-cardiovascular mortality, respectively. Similar U-shaped patterns were replicated in both men and women. Further analyses of cause-specific mortality subcategories showed that extremely high HDL cholesterol levels were also associated with increased mortality from heart disease, respiratory disease, endocrine disease, and cancer.ConclusionExtremely high levels of HDL cholesterol were associated with an increased risk of all-cause, cardiovascular, and non-cardiovascular mortality in the general population. Future studies should investigate the causal factors leading to the association of elevated HDL cholesterol and mortality.

Associations between risk of overall mortality, cause-specific mortality and level of inflammatory factors with extremely low and high high-density lipoprotein cholesterol levels among American adults