Median High-density Lipoprotein Cholesterol Research Articles

Abstract 13721: Coronary Artery Calcium for Risk Stratification Among Persons With Very-High High-Density Lipoprotein Cholesterol

Introduction: Persons with very-high high-density lipoprotein-cholesterol (HDL-C) may experience an increased mortality risk. However, the predictors of mortality among those with very-high HDL-C remain unknown. Hypothesis: Compared to traditional risk factors, coronary artery calcium (CAC) will more strongly stratify risk among individuals with very-high HDL-C. Aims: Among individuals with very-high HDL-C, to 1) calculate crude all-cause mortality rates across the burden of traditional risk factors and CAC, and 2) identify independent risk factors associated with all-cause mortality. Methods: There were 335 primary prevention patients from the CAC Consortium who had very-high HDL-C ( > 80 mg/dL in men, > 100 mg/dL in women) and available information on traditional CVD risk factors. Crude all-cause mortality rates were calculated per 1,000 person-years. Multivariable Cox proportional hazards regression assessed the association of traditional risk factors and CAC with mortality. Results: The mean age was 58.6 years old, 51.0% were women, 51.3% had prevalent CAC, and the median HDL-C was 100 mg/dL. There were 20 deaths (6.0%) over a median follow-up of 10.5 years, 7 (2.1%) of which were attributable to CVD. There was a stepwise higher crude mortality rate per 1,000 person-years across increasing CAC burden ( Central Illustration ). Independent of traditional risk factors, each 100 Agatston Unit increase in CAC score was associated with a 7% higher hazard of all-cause mortality (HR: 1.07, 95% CI: 1.01-1.12) and individuals with CAC > 1000 experienced a 5.75-fold higher hazard of mortality when compared to CAC=0 (HR: 5.75, 95% CI: 1.26-26.24). Beyond age, no traditional risk factor was associated with mortality in multivariable analyses. Conclusion: Measurement of CAC on non-contrast cardiac computed tomography may facilitate risk assessment among individuals with very-high HDL-C.

Cardiac valves calcification and HDL-C in patients with aortic valve sclerosis

Background and Aims : Growing evidence has demonstrated the influence of many atherosclerotic risk factors on cardiac valve calcification (CVC), which is correlated with higher cardiovascular and all-cause mortality risk. The aim of this study was to investigate the effect of high-density lipoprotein cholesterol (HDL-C) on both mitral and aortic valve calcification (AVC) in individuals with AVC.Methods: Sixty-four patients with AVC, prior the intervention, were prospectively enrolled and underwent blood sampling for biochemical analysis and multi-slice computed tomography (MSCT) without contrast. Primary end points were the quantification of (1) mitral annulus calcification (MAC) and AVC, calculated by the median MAC and AVC scores (both were defined by Agatston units (AU) according to MSCT findings) and (2) the HDL-C level (defined by a direct enzymatic method). The study took place between 3 tertiary hospitals in Greece from October 2019 to November 2020.Results: The median age of all participants was 75.3 years (IR=7.4). The median HDL-C, MAC and AVC score was 46.9 mg/dl (IR 12.4) and 737.4 AU (IR=1218.5), respectively. According to the bivariate analysis results, a statistically significant correlation was found between HDL-C levels and the MAC and AVC score, with increased levels of HDL-C being related to decreased levels of CVC (r=-0.318, p=0.014).Conclusions: A significant inverse correlation between the HLD-C and CVC was confirmed in individuals with AVC. The above findings raise great interest for further research on pathophysiological mechanisms of valvular calcification and suggest that HDL-C may be an important treatment target to attenuate the development and progress of CVC. Background and Aims : Growing evidence has demonstrated the influence of many atherosclerotic risk factors on cardiac valve calcification (CVC), which is correlated with higher cardiovascular and all-cause mortality risk. The aim of this study was to investigate the effect of high-density lipoprotein cholesterol (HDL-C) on both mitral and aortic valve calcification (AVC) in individuals with AVC. Methods: Sixty-four patients with AVC, prior the intervention, were prospectively enrolled and underwent blood sampling for biochemical analysis and multi-slice computed tomography (MSCT) without contrast. Primary end points were the quantification of (1) mitral annulus calcification (MAC) and AVC, calculated by the median MAC and AVC scores (both were defined by Agatston units (AU) according to MSCT findings) and (2) the HDL-C level (defined by a direct enzymatic method). The study took place between 3 tertiary hospitals in Greece from October 2019 to November 2020. Results: The median age of all participants was 75.3 years (IR=7.4). The median HDL-C, MAC and AVC score was 46.9 mg/dl (IR 12.4) and 737.4 AU (IR=1218.5), respectively. According to the bivariate analysis results, a statistically significant correlation was found between HDL-C levels and the MAC and AVC score, with increased levels of HDL-C being related to decreased levels of CVC (r=-0.318, p=0.014). Conclusions: A significant inverse correlation between the HLD-C and CVC was confirmed in individuals with AVC. The above findings raise great interest for further research on pathophysiological mechanisms of valvular calcification and suggest that HDL-C may be an important treatment target to attenuate the development and progress of CVC.

MO147: Fat Check: Lipid Abnormalities in Nephrotic Primary Glomerulopathies

Abstract BACKGROUND AND AIMS Lipid abnormalities are a defining feature of nephrotic syndrome. In nephrotic patients, changes such as increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) and decreased high-density lipoprotein cholesterol (HDL-C) as well as decreased HDL-C: TC ratio are more frequently found than in healthy subjects. The aims of this study were to evaluate the differences in the serum lipidic profile at baseline (diagnosis) among each primary glomerulopathies (PG) presenting with nephrotic syndrome (NS) and its association with several clinical parameters such as serum albumin (SAbl) and proteinuria. METHOD We conducted a retrospective cohort study with patients older than 18 years who presented with nephrotic syndrome and diagnosed with a PG by kidney biopsy in the last 10 years in a tertiary-level hospital. RESULTS The study included 60 patients: 38 were male (63.3%), with median age of 52 (IQR 27) years, 43.3% had hypertension, median serum creatinine (SCr) was 1.11 mg/dL (IQR 0.86), median protein-creatinine ratio was 7443 (IQR 5033.5) mg/g and median SAlb of 2.0 (IQR 1.03) mg/dL. At baseline, the median TC was 320.5 mg/dL (IQR 184.5), HDL-C 55 (IQR 25.5) mg/dL, LDL-C 225mg/dL (IQR 174), TG 176 (IQR 122.6) mg/dL and HDL: TC ratio 0.19 (IQR 0.13). Median follow-up time was 24 (IQR 51) months. Patients were grouped in four categories regarding the PG subtype: membranous nephropathy (MN, 38.3%), minimal change disease (MCD, 38.3%), IgA nephropathy (IgAN, 11.7%) and focal segmental glomerulosclerosis (FSGS, 11.7%). Evaluating all the patients enrolled, we found a strong negative correlation between SAlb and TC (r = –0.511, P < .001), LDL-C (r = –0.529, P < .001) and a weaker negative correlation with TG (r = –0.282, P = .030), but not with HDL-C. We did not find a statistically significant correlation between proteinuria and each cholesterol subtype or TG levels. A Kruskal–Wallis test showed that different subtypes of PG were associated with different median HDL-C (H(3) = 12.073, P = .007) and TG serum levels (H(3) = 10.128, P = .018). No statistically significant differences in the TC, LDL-C or HDL-C: TC ratio were found. Comparing all pairs of groups, we found that HDL-C levels were statistically different between MN and MCD (45.5 versus 67 mg/dL, P < .001), but not in the other pairs. The same analysis found that TG serum levels were only significantly different between IgAN and MN (114 versus 187 mg/dL, P = .008) and between IgAN and FSGS (114 versus 200 mg/dL, P = .012). MN patients that progressed to CKD stage 5D had lower median HDL-C levels at diagnosis, when compared to the patients who did not progress (41 versus 49 mg/dL, P = .037). This difference was not observed in IgA, FSGS or MCD. CONCLUSION Each GP subtype presents a different lipid profile, particularly differing on HDL and TG. Patients with MCD presented with the highest levels of HDL-C, while MN with the lowest. Regarding TG levels, FSGS presented with the highest levels while IgAN presented with the lowest. In the membranous nephropathy group, patients that progressed to ESRD had statistically significantly lower serum levels of HDL-C. As expected, SAlb is significantly associated with TC, LDL-C and TG levels, in nephrotic patients. This could be due to different levels of lecithin–cholesterol acyltransferase (an enzyme responsible for the maturation of HDL), which is increasingly lost through urine in nephrotic syndromes. The differences found in the lipidic profile between PG subtypes could have screening, therapeutic and prognosis implications in the management of cardiovascular risk in these patients. More studies are needed to understand the pathophysiology and the prognosis significance of each lipid profile.

Intensification of lipid-lowering therapy in very high-risk patients: potential of combination with PCSK9 inhibitors

Aim. To assess the efficacy and safety of 6-month combined lipid-lowering therapy with a PCSK9 inhibitor in patients with very high cardiovascular risk (CVR).Material and methods. This prospective, open-label, single-center exploratory research study with active treatment included 5 outpatients with very high CVR. So, 80% of patients had prior coronary artery disease, 20% peripheral arterial disease, and 60% old myocardial infarction. The key inclusion criterion was the failure to achieve the target low-density lipoprotein cholesterol (LDL-C) <1,4 mmol/l with high-intensity statin monotherapy at the maximal tolerated doses or combination therapy with ezetimibe. On a regular basis, all included patients took atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day, or pitavastatin 2-4 mg/day. In addition, 2 patients received a statin in combination with ezetimibe 10 mg/day. Patients were followed up for 6 months as follows: every 2 weeks, with a lipid profile monitoring, subcutaneous injections of alirocumab at a dose of 150 mg/ml were performed. Additionally, clinical and laboratory indicators of the safety of therapy were evaluated.Results. After 6 months, with the combined lipid-lowering therapy with alirocumab, a decrease in median LDL-C from 4,3 (4,11-4,67) to 1,27 (1,06-1,47) (p=0,001) mmol/l, total cholesterol from 6,1 (6-7) to 3,7 (3,5-3,9) (p=0,018) mmol/l, atherogenic index from 3,2 (3-3,26) to 0,8% (0,8-1,5) (p=0,001). There was no significant decrease in median triglycerides and an increase in median high-density lipoprotein cholesterol. Six-month lipid-lowering therapy with a PCSK9 inhibitor had no adverse events and made it possible to achieve a maximum decrease in LDL-C by an average of 75,4% already by 4 months of treatment in actual clinical practice.Conclusion. Six-month combined lipid-lowering therapy with alirocumab 150 mg subcutaneously every 2 weeks in very high-risk patients allows the majority of patients to achieve target LDL-C values.

Whole-blood magnesium and blood lipids are individually and jointly associated with an elevated likelihood of youngsters being overweight or obese: A matched case-control study using the propensity score

ObjectivesYoungsters who are overweight or obese (YOO) have become an important global health concern. Some micronutrients may be modifiable influential factors. This study aimed to investigate the individual and joint association of whole-blood magnesium (WBMg) and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in YOO. MethodsThis is a propensity score matching-based case-control study. YOO was defined depending on age- and sex-specific body mass index z-score, calculated with SAS macros (%group_standard and %WHO2007) from the World Health Organization website. WBMg, blood lipids, and covariates were carefully measured by trained technicians using a whole-blood, five-element, basic analyzer and atomic absorption spectrometer or automatic biochemical analyzer. Locally weighted scattered plot smoothing and multivariable conditional logistic regression models were applied to estimate the associations of WBMg and blood lipids in YOO. ResultsWBMg was positively associated with YOO. The adjusted likelihood of YOO significantly increased by 21% (odds ratio: 1.21; 95% confidence interval [CI], 1.10–1.33) with per-interquartile range elevation of WBMg. Compared with the 1st quartile, adjusted odds ratios among youngsters in the 2nd, 3rd, and 4th quartiles of WBMg were 1.11 (95% CI, 0.92–1.35), 1.29 (95% CI, 1.06–1.57), and 1.47 (95% CI, 1.18–1.83), respectively. Furthermore, the relationship between WBMg and YOO was moderated by lipid profiles. Compared with those having lower (< median) WBMg and TC, TG, LDL-C, or higher (≥ median) HDL-C, youngsters with both higher WBMg and TC, TG, LDL-C, or lower HDL-C had higher YOO odds, which averagely increased by 188%, 250%, 339%, and 369%, respectively. ConclusionsWBMg was an independent risk factor of YOO, and the associations were stronger among those with unhealthy blood lipids. Our findings can help to guide clinical and public health policies on the relevance of magnesium nutritional status.

Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk

It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk. To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk. A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa. Participants were randomized to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins. The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. When 1384 patients had experienced a primary end point event (of a planned 1600 events), the trial was prematurely halted based on an interim analysis that indicated a low probability of clinical benefit of omega-3 CA vs the corn oil comparator. Among the 13 078 treated patients (mean [SD] age, 62.5 [9.0] years; 35% women; 70% with diabetes; median low-density lipoprotein [LDL] cholesterol level, 75.0 mg/dL; median triglycerides level, 240 mg/dL; median HDL-C level, 36 mg/dL; and median high-sensitivity C-reactive protein level, 2.1 mg/L), 12 633 (96.6%) completed the trial with ascertainment of primary end point status. The primary end point occurred in 785 patients (12.0%) treated with omega-3 CA vs 795 (12.2%) treated with corn oil (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). A greater rate of gastrointestinal adverse events was observed in the omega-3 CA group (24.7%) compared with corn oil-treated patients (14.7%). Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients. ClinicalTrials.gov Identifier: NCT02104817.

Association between plasma HDL-C levels and coronary artery severity and impact on outcomes of patients underwent percutaneous coronary intervention

Objective: To analyze the association between plasma high-density lipoprotein cholesterol (HDL-C) levels and the severity of coronary artery disease, and to evaluate the impact of HDL-C levels on long-term outcomes in patients underwent percutaneous coronary intervention (PCI). Methods: A total of 10 458 consecutive patients underwent PCI from January 2013 to December 2013 at Fuwai hospital were enrolled in this study. Patients were divided into three groups according to HDL-C tertiles: low HDL-C group (HDL-C≤0.89 mmol/L, n=3 525), median HDL-C group (HDL-C>0.89-1.11 mmol/L, n=3 570) and high HDL-C group (HDL-C>1.11 mmol/L, n=3 363). SYNTAX score was used to evaluate the severity of coronary artery disease, linear regression was used to analyze the relationship of HDL-C and SYNTAX score. Kaplan-Meier survival analysis was used to compare the outcomes among the three groups. Multivariate Cox regression was used to define the potential associations of HDL-C and outcomes. Results: The HDL-C level was (1.03±0.28) mmol/L and the SYNTAX score was 11.7±8.1. Patients were older, proportion of female, stable angina pectoris, successful PCI and left ventricular eject fraction value were higher, while incidence of diabetes mellitus was lower, hyperlipidemia, old myocardial infraction, smoking history and left main and three vessels disease were lower in high HDL-C group (all P<0.05). Patients in high HDL-C group also had the lowest SYNTAX score (12.2±8.4 vs. 11.7±8.1 vs. 11.2±7.8, P<0.001). Both univariate and multivariate linear regression analysis showed that HDL-C was negatively associated with SYNTAX score, e.g. Univariate analysis: β=-0.046, P<0.001; Multivariate analysis: β=-0.058, P=0.001. And 10 400 (99.4%) patients completed 2-year follow up. At 2-year follow-up, there were no difference in all-cause death, cardiac death, myocardial infarction, revascularization, stroke, major adverse cardiovascular and cerebral events (MACCE) and stent thrombosis among three groups (P for trend>0.05), while patient in high HDL-C group experienced the highest BARC type 2 bleeding events (P for trend=0.018). Multivariate Cox regression analysis showed that HDL-C level was not an independent risk factor of 2-year adverse ischemia events (P>0.05) and 2-year bleeding events (P>0.05). Conclusion: In patients underwent PCI, plasma HDL-C level is negatively associated with SYNTAX score, but not an independent risk factor of ischemic and bleeding events post PCI.

Abstract 21062: Association Between High-Density Lipoprotein Cholesterol With All-Cause Death and Cardiovascular Events in a Primary Prevention Population

Introduction: Higher levels of high density lipoprotein cholesterol (HDL-C) are associated with reduced risk of cardiovascular disease (CVD). However, observational data suggest very high HDL-C may be associated with increased all-cause mortality. We aimed to investigate the relationship between HDL-C and CV mortality and morbidity. Methods: Using data from adults without prior CVD from 5 large U.S.-based cohorts available through NIH BioLINCC (Framingham Cohort Study, Framingham Offspring, Multi-ethnic Study of Atherosclerosis, Atherosclerosis Risk in Communities, and Cardiovascular Health Study), we assessed the association between HDL-C and all-cause death and CVD composite events (CV death, myocardial infarction, angina, or stroke) using Cox proportional hazards models, modeling HDL-C with restricted cubic splines to allow for non-linearity. Adjustment factors included age, race, systolic blood pressure, antihypertensive medications, diabetes, body-mass index, smoking status, low-density lipoprotein cholesterol, and weekly alcohol use. Results: Among 22,569 individuals (median age 56 years, 55% women), median (IQR) HDL-C was 50 mg/dL (41, 62). Those with HDL-C&gt;50 mg/dL were more frequently female, non-smokers, and less obese. Over median follow up of 19.5 years, 6,539 deaths occurred (31% CV deaths). After adjustment for clinical factors, there was a U-shaped association between HDL-C and all-cause death in men, and to a lesser degree in women (Figure). As compared with a reference point of 50 mg/dL, lower HDL-C was associated with higher CVD composite events in both men and women, but higher HDL-C was not associated with increased CVD composite risk in either sex. Conclusions: In this large, U.S.-based study of well-characterized clinical cohorts and long-term follow-up, HDL-C displayed a U-shaped relationship with all-cause death. Low, but not high, HDL-C is associated with higher CVD composite events in both men and women.

Advanced Lipid Testing Uncovers Hidden Cardiovascular Disease Risk: A Case Control Analysis

Lead Author’s Financial Disclosures: None Study Funding: This study was funded by Boston Heart Diagnostics on a contract and approved protocol with the Cardiovascular Research Institute, University of California, San Francisco, CA. All analyses were run in a blinded fashion. Background/Synopsis: Recommended standard lipid testing includes total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and calculated low density lipoprotein cholesterol (LDL-C), which many healthcare providers view as providing insufficient information about cardiovascular disease (CVD) risk. Objective/Purpose: To compare standard lipid profile testing with advanced lipid and inflammatory marker analysis in a CVD case-control study. Methods: In addition to standard methods, we measured serum direct LDL-C, small dense LDL-C (sdLDL-C), very low density lipoprotein cholesterol (VLDL-C), apolipoprotein (apo) B, apoA-I, lipoprotein(a) or Lp(a), HDL particles by gel electrophoresis and apoA-I immunoblotting, high sensitivity C reactive protein (hsCRP), and serum amyloid A (SAA) in 298 documented CVD cases (mean age 68.4 years, 54% male, 46% female) and 609 age and gender matched controls. All subjects were off lipid altering medications. All cases were sampled more than 4 weeks after any CVD event. All subjects had blood drawn after an overnight fast. Results: In male and female cases, median TC levels were 1% and 3% higher, TG levels 19% and 29% higher, direct LDL-C 2% and 17% higher, sdLDL-C 46% and 46% higher, VLDL-C 22% and 4% higher, apoB 6% and 17% higher, and Lp(a) 26% and 70% higher, respectively, than in matched controls. In male and female cases, median HDL-C levels were 25% and 26% lower, apoA-I 9% and 7% lower, while apoA-I values in HDL particles were 30% and 26% lower in very large a-1 HDL, 9% and 11% lower in large a-2 HDL, 4% and 4% lower in medium a-3 HDL, 13% and 6% lower in small a-4 HDL, and 16% and 15% higher in very small preb-1 HDL as compared to matched controls. In male and female cases, median hsCRP levels were 113% and 178% higher, and SAA levels were 41% and 43% higher than in matched controls. Values for sdLDL-C, Lp(a), apoA-I in preb-1 HDL and a-1 HDL, hsCRP, and SAA were all significantly different (p,0.001) in male and female cases versus controls. Conclusions: Our results indicate that advanced lipid and inflammatory marker testing provides significantly more information distinguishing CVD cases from controls than does standard lipid testing. Our data supports the use of advanced testing in CVD prevention, especially in CVD patients being considered for proprotein convertase subtilisin/kexin type 9 inhibitor therapy.

Extended-Release Niacin Versus Fenofibrate in HIV-Infected Participants With Low High-Density Lipoprotein Cholesterol: Effects on Endothelial Function, Lipoproteins, and Inflammation.

Low levels of high-density lipoprotein cholesterol (HDL-C) are common in individuals with human immunodeficiency virus (HIV) infection, persist during antiretroviral therapy (ART), and are associated with increased cardiovascular disease (CVD) risk. Virologically controlled participants without CVD on stable ART with low HDL-C (men <40 mg/dL, women <50 mg/dL) and triglycerides >150 mg/dL were randomized to receive open-label extended-release niacin 1500 mg/day with aspirin 325 mg/day or fenofibrate 200 mg/day for 24 weeks. The primary endpoint was the week 24 within-arm change in brachial artery flow-mediated dilation (FMD) in participants with complete follow-up scans. Of 99 participants, 74 had complete data (35 niacin, 39 fenofibrate). Median age was 45 years, 77% were male, median CD4(+) count was 561 cells/µL, and brachial FMD was 4.2%. Median HDL-C was 32 mg/dL for men and 38 mg/dL for women, low-density lipoprotein cholesterol was 103 mg/dL, and triglycerides were 232 mg/dL. In men, HDL-C increased a median of 3 mg/dL with niacin and 6.5 mg/dL with fenofibrate (P < .001 for both). In women, HDL-C increased a median of 16 mg/dL with niacin and 8 mg/dL with fenofibrate (P = .08 for both). After 24 weeks, there was no significant change in FMD in either arm; the median (interquartile range) change was +0.6% (-1.6 to 2.3) with niacin (P = .28) and +0.5% (-1.0 to 3.0) with fenofibrate (P = .19). Neither treatment significantly affected C-reactive protein, interleukin 6, or D-dimer levels. Despite improvements in lipids, niacin or fenofibrate treatment for 24 weeks did not improve endothelial function or inflammatory markers in participants with well-controlled HIV infection and low HDL-C. NCT01426438.

The characteristics of serum high-density lipoprotein cholesterol levels in urban population from Tangshan City

Objective To understand the characteristics of High-density lipoprotein cholesterol(HDL-C) distribution through analyzing serum HDL-C levels in healthy checkup subjects among local urbanese. Methods The checkup results of 36 454 cases were collected from 2009 to 2013 in Tangshan Gongren hospital(male: n=20 343, female: n=16 111). The cases with liver injury, abnormal blood glucoses , kidney injury and defined cerebrovascular diseases and metabolic disease were excluded. 25 197 cases were analyzed as normal subjects including 11 114 males and 14 083 females. Kolmogorov-Smimov test, kruskal-wallis test, and Dunn multiple comparison test was performed using Bioconductor software 3.0.2 for testing normality distribution and comparing the difference of two or multiple groups, respectively. Results were analyzed statistically with R 3.0.2. Results The results showed that the average level (1.22 ± 0.31) mmol/L of HDL-C among the overall population is lower than that of national average level(1.30 mmol/L). The median serum HDL-C level in female is higher than in male (1.27 and 1.08, χ2=2 606.34, P<0.01). HDL-C levels in male continuously increase from 1.06 mmol/L to 1.11 mmol/L with aging, especially in groups of over 50 years old than in groups of below 50 years old (χ2=75.19, P<0.01). Conclusions Based on 2007 guidance on prevention and treatment by national health bureau, this study showed that there are 29.69% of the apparent healthy subjects, especially about 42.94% of the male, representing low HDL-C level under the low limit of 1.04 mmol/L. These results showed that serum HDL-C level in Tangshan urbanese is lower than that of national average level, and HDL-C level in male is tended to increase with aging. Key words: Cholesterol, HDL; Physical examination; Retrospective studies

Abstract 16133: High Density Lipoprotein Cholesterol is an Alternative Marker to Troponin for Acute Coronary Syndrome in High Risk Patients

Introduction: It is well known that high density lipoprotein cholesterol is inversely correlated with the risk of coronary artery disease. However, data is limited regarding the relationship of high density lipoprotein cholesterol in the acute setting of coronary artery disease and particularly how it compares to the most well-known biomarker, cardiac troponin I. Hypothesis: We assessed the hypothesis that high density lipoprotein cholesterol could be used as an alternative marker to troponin for acute coronary syndrome (ACS) in high risk patients. Methods: We analysed 740 patients of the BRAVEHEART cohort presenting for coronary angiography at our institution between October 2009 and March 2014. Of these, 153 patients presented with ACS, including 44 with ST elevation myocardial infarction and 109 with non-ST elevation myocardial infarction, and 587 patients presented without ACS. Binary logistic regression was used to compare high density lipoprotein cholesterol and cardiac troponin I levels as predictors of ACS, independent of age, sex, cardiac risk factors and statin use. Results: Patients presenting with ACS had higher median cardiac troponin I levels (0.34 vs. 0.02 μg/L; p&lt;0.001), higher median serum triglyceride levels (1.5 vs. 1.3 mmol/L, p&lt;0.001) and lower median high density lipoprotein cholesterol levels (0.97 vs. 1.09 mmol/L, p&lt;0.001) than patients without ACS. There was no difference in total cholesterol and low density lipoprotein cholesterol between the two groups. After adjusting for differences in patient variables, the strongest independent predictors of ACS were cardiac troponin I (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.24-1.82; p&lt;0.001) and high density lipoprotein cholesterol (OR, 0.12; 95% CI, 0.04-0.36; p&lt;0.001). Conclusion: In conclusion, high density lipoprotein cholesterol was found to be an independent marker of ACS in high risk patients at our institution. Further studies on high density lipoprotein cholesterol could determine its clinical use in conjunction with troponin levels in patients presenting with ACS.

Prospective Analysis Of Plasma Cholesterol and Triglycerides In Patients (pts) With Chronic Phase (CP)-Chronic Myeloid Leukemia (CML) During Treatment With The 2nd Generation Tyrosine Kinase Inhibitor (TKI) Nilotinib

BackgroundNilotinib is approved for use in pts with CML after failure of imatinib and in newly diagnosed CP-CML. In the ENESTnd trial, 1st line nilotinib was associated with a higher frequency of hypercholesterolemia than imatinib. Moreover, several studies reported a nilotinib-associated risk of artery occlusive disease (AOD). In ENESTnd, pre-existing treatment for dyslipidemia did not preclude pts from enrolment. To avoid this pitfall and to determine which cholesterol fractions are affected and whether triglycerides (TG) are modified, we prospectively studied the plasma lipid profile of nilotinib-treated pts without drug treatment for dyslipidemia. MethodsPts (n=25) in our center with CP-CML either newly diagnosed or after failure of imatinib were proposed 1st or 2nd line nilotinib provided that neither very high risk for fatal cardiovascular disease (CVD) nor nilotinib-resistant ABL kinase domain mutation were present at baseline. Pts with drug treatment for dyslipidemia at baseline were excluded from this study. Total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and TG were measured prior to the start of nilotinib and at 3, 6, 9 and 12 months. Fasting glucose (FG) and glycosylated hemoglobin (HbA1C) were also measured. Results are shown as medians (min-max). ESC/EAS 2012 guidelines were used to determine CVD risk categories and for the management of dyslipidemias. ResultsMedian age at nilotinib initiation was 52 years (19-69), 13 were males (52%). Sokal risk group was low in 11 pts (44%), intermediate in 11 (44%) and high in 3 (12%). Nilotinib was given upfront in 20 pts (80%) and after 1st line imatinib in 5 pts (20%). Median time from diagnosis was 0.8 month (0.4-4.3) in the former and 15.7 months (2.5-47.9) in the latter. Initial nilotinib dosing regimen was 300mg BID in 22 pts (88%) and 400mg BID in 3 pts (12%). Baseline CVD risk factors included age ≥ 45 years in men and ≥ 55 years in women in 33 pts (52%), active smoking or ceased during the previous year in 6 pts (24%), body mass index (BMI) ≥ 25 kg/m2in 14 pts (56%), hypertension in 1 pt (4%), type 2 diabetes mellitus (DM) in 1 pt (4%). Two pts were discovered pre DM. The CVD risk was low in 12 pts (48%), moderate in 11 pts (44%) and high in 2 pts (8%).At baseline, no pt required drug intervention by lipid lowering agents based on LDL-C, 11 pts (44%) had low HDL-C (≤0.4g/L) and 7 (28%) had high TG (≥1.5g/L). Median FG and HBA1C were 0.88g/L (0.63-1.26) and 5.5% (4.7-6.5), respectively. All pts were given lifestyle medical advice. At M3, TC, LDL-C and HDL-C had increased by a mean of 26.9%, 31.8% and 36.3%, respectively. Median TC at baseline and M3 was 1.84g/L (1.17-2.74) and 2.27g/L (1.08-3.62) (p<0.0001). Median LDL-C at baseline and M3 was 1.13g/L (0.69-2.02) and 1.45g/L (0.68-2.7) (p=0.00012). Median HDL-C at baseline and M3 was 0.42g/L (0.16-0.77) and 0.55g/L (0.27-0.99) (p<0.0001). Only 3 pts (12%) had low HDL-C at M3. In contrast, TG decreased by a mean of -22.3%. Median TG at baseline and M3 was 1.02g/L (0.38-4.18) and 0.8g/L (0.41-3.83) (p=0.0003). Only 2 pts (8%) had high TG at M3. No further significant change was observed beyond M3 with median TC, LDL-C, HDL-C and TG at M12 of 2.2g/L (1.15-2.9), 1.3g/L (0.69-1.84), 0.52g/L (0.38-1.27) and 0.83g/L (0.37-1.61), respectively. Finally, 1 pt developed type 2 DM at M12.Three pts (12%) required statins during the first year of nilotinib therapy: 2 pts with a moderate CVD risk at baseline and in whom LDL-C rose above 1.9g/L and 1 pt with a moderate CVD risk at baseline who developed peripheral artery disease (PAD) at M12, leading to nilotinib discontinuation. By M12, the CVD risk changed from low to high in 1 pt due do to the onset of DM and from moderate to very high in the pt with PAD. ConclusionsNilotinib is associated with a significant and early increase in TC, LDL-C and HDL-C. In contrast, a decrease in TG occurs but this may be due to lifestyle medical advice given to our patients. All patients considered for nilotinib therapy should have an evaluation of blood lipids at baseline and early after the start of therapy. Requirement for lifestyle modifications and lipid lowering treatment by statins should be determined at baseline and throughout therapy according to TC, LDL-C and CVD risk category. The role of nilotinib-induced high LDL-C in the onset of AOD needs to be investigated. Disclosures:Rea:Novartis: Honoraria; BMS: Honoraria; Teva: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Gautier:Novartis: Honoraria. Messas:Novartis: Honoraria. Dombret:Novartis: Research Funding.

Abstract 1362: Dyslipidemia, excess weight and high mammographic density are associated with high levels of daily estrogen and progesterone. .

Abstract Background: Dyslipidemia, excess weight, and high mammographic density have independently been associated with breast cancer development. However, little is known regarding the combined effect of dyslipidemia, excess weight and mammographic density on cyclic variation in estrogen and progesterone. Material and Methods: 202 premenopausal women (25-35 years) participated in the Norwegian EBBA-I study including clinical examinations, and fasting blood sampling. Computer-assisted percent mammographic density (Madena) was obtained from digitized mammograms taken at day 7-12 of menstrual cycle. Daily saliva samples were collected across an entire menstrual cycle, and concentrations of 17β-estradiol and progesterone were measured at the Reproductive Ecology Laboratory, Harvard University, USA. Uni and multivariable linear and logistic regression models were used to study the combined association of high-density lipoprotein cholesterol (HDL-C), body mass index (BMI) and mammographic density with daily concentrations of 17β-estradiol and progesterone. Results: Among women with mean age of 30.7 years, mean percent mammographic density 29.8 %, mean BMI 24.4 kg/m2, mean total cholesterol 4.45 mmol/l, and mean HDL-C 1.54 mmol/l, we observed overall mean salivary 17β-estradiol 16.2 pmol/l and progesterone 129.3 pmol/l. We used median split and women characterized by lower than median HDL-C (≤ 1.51 mmol/l), higher than median BMI (&amp;gt; 23.6 kg/m2), and higher than median percent mammographic density (&amp;gt; 28.5 %) (unfavorable profile), had higher concentrations of both 17β-estradiol (p = 0.005) and progesterone (p = 0.016) across the entire menstrual cycle, compared with women characterized by higher HDL-C(&amp;gt; 1.51 mmol/l), lower BMI (≤ 23.6 kg/m2) and lower percent mammographic density (≤ 28.5 %) (favorable profile). Comparing the profiles, women with an unfavorable profile had 46 % higher overall mean 17β-estradiol (17β-estradiol; 22.2 versus 15.9 pmol/l) and 48% higher overall mean progesterone (progesterone; 187.5 versus 126.1pmol/l). These factors also showed strong associations with differences in AUC (area under curve) of these sex steroid hormones across the entire menstrual cycle, reflecting cumulative exposure. Women characterized by unfavorable profile had 48 % higher AUC estradiol compared with women having favorable profile (AUCe, 387, 95 % confidence interval (CI) 244 - 531 versus 262, 95% CI 244 - 281). Furthermore, women with unfavorable profile had 47 % higher AUC progesterone than women with favorable profile (AUCp, 1929, 95 % CI 1125 - 2733 versus 1309, 95% CI 1211 -1408). Conclusion: A combination of low HDL-C, excess weight, and high percent mammographic density, was strongly associated with higher daily levels of 17β-estradiol and progesterone, and could in part explain the association of these factors with increased risk of breast cancer development. Citation Format: Vidar G. Flote, Hanne Frydenberg, Giske Ursin, Anita Iversen, Morten W. Fagerland, Peter T. Ellison, Erik A. Wist, Thore Egeland, Anne-Sofie Furberg, Inger Thune. Dyslipidemia, excess weight and high mammographic density are associated with high levels of daily estrogen and progesterone. . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1362. doi:10.1158/1538-7445.AM2013-1362

Low Total, Low-Density Lipoprotein, High-Density Lipoprotein, and Non–High-Density Lipoprotein Cholesterol Levels in Patients with Complex Congenital Heart Disease after Fontan Palliation

To test the hypothesis that patients with complex congenital heart disease who have undergone Fontan palliation have low total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. We retrospectively reviewed the random serum lipid profiles obtained at cardiology clinic visits between May 2010 and November 2011 in patients who had undergone the Fontan procedure. We compared these serum lipid levels against age- and sex-matched established normal data from the Third National Health and Nutrition Examination Survey. Eighty-eight patients who had undergone the Fontan procedure also had laboratory test data obtained during their visits. Median total cholesterol level in the Fontan group was 127 mg/dL (IQR, 116-144 mg/dL), median HDL-C was 40 mg/dL (IQR, 33-45 mg/dL), median non-HDL-C was 86 mg/dL (IQR, 76-109 mg/dL), and median LDL-C was 66 mg/dL (IQR, 57-83 mg/dL). Total cholesterol, LDL-C, non-HDL-C, and HDL-C levels were significantly lower in patients who had undergone a Fontan procedure compared with age- and sex-matched normal individuals (mean z-score, -1.4, -1.2, -1.0, and -1.0 respectively; all P<.0001). Cholesterol levels were below the 25th percentile for age and sex for total cholesterol in 82% of patients, for LDL-C in 76%, for non-HDL-C in 67%, and for HDL-C in 57%. Patients who have undergone the Fontan procedure have significantly lower serum total cholesterol, LDL-C, HDL-C and non-HDL-C levels than age- and sex-matched normal individuals. Although the implications of this finding are unknown, it raises the possibility of abnormalities in cholesterol absorption, synthesis, or catabolism in this patient population.

High-density cholesterol and apolipoprotein AI as modifiers of plasma fibrin clot properties in apparently healthy individuals

Low high-density lipoprotein cholesterol (HDL-C) increases cardiovascular risk, whereas its high levels protect against atherosclerosis via multiple beneficial effects. Dense and poorly lysable fibrin clot formation is observed in cardiovascular disease. We sought to investigate whether HDL-C and its major component apolipoprotein A (Apo A)-I affect fibrin clot properties. In 136 apparently healthy individuals (99 men, 37 women, aged 49-69 years) we determined plasma fibrin clot permeability (Ks coefficient) and lysis time (t50%) together with Apo A-I and lipoprotein (a) [Lp(a)] levels. The median HDL-C level was 1.33 mmol/l (range from 0.77 to 2.19 mmol/l). HDL-C was positively associated with Apo A-I (r = 0.62, P < 0.00001). HDL-C and Apo A-I were positively correlated with Ks (r = 0.52, P < 0.00001 and r = 0.44, P < 0.00001, respectively) and inversely with t50% (r = -0.44, P < 0.00001 and r = -0.35, P = 0.00003, respectively). No such associations were seen for other lipid variables. Ks and t50% were associated with Lp(a) (r = -0.42, P < 0.00001 and r = 0.42, P < 0.00001, respectively) and fibrinogen (r = -0.31, P = 0.00024 and r = 0.39, P < 0.00001, respectively). Individuals with HDL-C at least 1.4 mmol/l (n = 54) had 19% higher Ks (P = 0.00016) and 17% shorter t50% (P = 0.0012) than the remainder. After adjustment for age, fibrinogen, and Lp(a), HDL-C was the independent predictor of Ks (β = 0.7, P < 0.00001) and t50% (β = -0.62, P < 0.00001). This study shows that elevated HDL-C levels are associated with improved fibrin clot permeability and lysis, indicating a novel antithrombotic mechanism underlying the postulated beneficial effects of therapy targeted at HDL-C.

Impact of high-density lipoprotein levels at hospital admission on the outcome of patients with acute ST-segment elevation myocardial infarction

To analyze the impact of high-density lipoprotein cholesterol (HDL-C) levels at hospital admission on the incidence of major adverse cardiovascular events (MACCE) in patients with acute ST segment elevation myocardial infarction (ASTEMI). 1067 patients with ASTEMI who were admitted to the 20 hospitals in Liaoning region and with lipid profile tested within the 24 hours of admission from May 2009 until May 2010, were enrolled. Data on basic demographic, clinical, status on admission and method of treatment were collected. Rate on various medical use and MACCE (cardiovascular death, non-fatal myocardial infarction, revascularization and stoke) were compared between the two groups through follow-up observation. Cox proportional hazard analysis was estimation. The median HDL-C level was 1.27 mmol/L, with 587 patients having HDL-C below and 489 patients HDL-C above the median level. The incidence rates of non-fatal myocardial infarction and MACCE at one-year follow-up period, was higher in low HDL-C group (4.8% vs. 0.9%, P<0.001; 23.7% vs. 18.1%, P=0.03, respectively). At one month follow-up, the incidence rate of non-fatal myocardial infarction was higher in low HDL-C group (1.4% vs. 0.0%, P=0.01). At six month follow-up, the incidence rates of non-fatal myocardial infarction and MACCE on one-year follow-up was higher in low HDL-C group (2.8% vs. 0.4%, P=0.003; 18.3% vs. 13.7%, P=0.04, respectively). from Cox proportional hazards analysis indicated that age (HR=1.02, 95%CI: 1.006-1.035, P=0.005), diabetes (HR=1.05, 95%CI: 1.053-2.171, P=0.03), HDL-C level (HR=0.56, 95%CI: 0.340-0.921, P=0.02) were significantly related to the incidence of MACCE. The incidence rates of one year and six month MACCE (mainly non-fatal myocardial infarction) and one month non-fatal myocardial infarction were significant higher in patients with low than high HDL-C levels at admission while kept on the ascending along with time. Age, diabetes, HDL-C level were independent risk factors related to the incidence of MACCE.

Influence of the Combination of Low-Density Lipoprotein Receptor and Interleukin 28B Genotypes on Lipid Plasma Levels in HIV/Hepatitis C-Coinfected Patients

Influence of the Combination of Low-Density Lipoprotein Receptor and Interleukin 28B Genotypes on Lipid Plasma Levels in HIV/Hepatitis C-Coinfected Patients

Short-term effects of extended-release niacin on endothelial function in HIV-infected patients on stable antiretroviral therapy

To assess the short-term effects of extended-release niacin (ERN) on endothelial function in HIV-infected patients with low high-density lipoprotein-cholesterol (HDL-c) levels. Randomized controlled study to determine the short-term effects of ERN on endothelial function, measured by flow-mediated vasodilation (FMD) of the brachial artery, in HIV-infected adults with low HDL-c. Participants on stable HAART with fasting HDL-c less than 40 mg/dl and low-density lipoprotein-cholesterol less than 130 mg/dl were randomized to ERN or control arms. ERN treatment started at 500 mg/night and titrated to 1500 mg/night for 12 weeks. Controls received the same follow-up but were not given ERN (no placebo). Participants were excluded if they had a history of cardiac disease, uncontrolled hypertension, diabetes mellitus, or were on lipid-lowering medications such as statins and fibrates. Change in FMD was compared between arms with respect to baseline HDL-c. Nineteen participants were enrolled: 89% men, median age 50 years, 53% white/non-Hispanic, median CD4 cell count 493 cells/microl, and 95% of them had HIV RNA below 50 copies/ml. Participants receiving ERN had a median HDL-c (interquartile range) increase of 3.0 mg/dl (0.75 to 5.0) compared with -1.0 mg/dl in controls (-6.0 to 2.5), a P value is equal to 0.04. The median change in FMD was 0.91% (-2.95 to 2.21) for ERN and -0.48% (-2.65 to 0.98) for controls (P = 0.67). However, end of study FMD for ERN was significantly different from controls after adjusting for baseline differences in FMD and HDL-c, 6.36% (95% confidence interval 4.85-7.87) and 2.73% (95% confidence interval 0.95-4.51) respectively, a P value is equal to 0.048. This pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected patients with low HDL-c.

Seasonal Variation in Lipids in Patients Following Acute Coronary Syndrome on Fixed Doses of Pravastatin (40 mg) or Atorvastatin (80 mg) (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22 [PROVE IT-TIMI 22] Study)

Previous studies have shown seasonal variation in lipids. To understand whether this variation exists in patients with acute coronary syndromes receiving statins, we examined data from the PROVE IT-TIMI 22 Study. At baseline, no significant difference in low-density lipoprotein (LDL) cholesterol was observed when stratified by season. However, a statistically significant difference in high-density lipoprotein cholesterol between winter (37 mg/dl) and summer (39 mg/dl) was observed (p <0.001) at baseline. On treatment, median LDL cholesterol was 102 mg/dl in winter versus 96 mg/dl in summer (p <0.001) for the pravastatin group and 68 mg/dl in winter versus 62 mg/dl in summer (p <0.001) for the atorvastatin group. Median high-density lipoprotein cholesterol was 43 mg/dl in summer versus 41 mg/dl in winter in the pravastatin group and 42 mg/dl in summer versus 39 mg/dl in winter in the atorvastatin group (p <0.001). More patients achieved LDL cholesterol <100 mg/dl in summer at 56% versus 47% in winter in the pravastatin group (p <0.001) and 89% versus 87% in winter for the atorvastatin group (p = 0.11). Achievement of LDL cholesterol <70 mg/dl was also higher in summer than winter. In conclusion, this was the first evidence of seasonal variability in cholesterol in patients with acute coronary syndromes treated with statins. This variability affected achievement of National Cholesterol Education Program goals and may affect management decisions based on season of collection.