High Lipoprotein Research Articles

Impact of a Physical Exercise and Health Education Program on Metabolic Syndrome and Quality of Life in Postmenopausal Breast Cancer Women Undergoing Adjuvant Treatment with Aromatase Inhibitors.

Background and Objectives: Adjuvant treatment with aromatase inhibitors (AIs) in breast cancer (BC) survivors can cause adverse effects such as metabolic syndrome (MS) (insulin resistance, central obesity, atherogenic dyslipidemia, and hypertension) associated with morbidity and premature mortality. We evaluate the effect of a multimodal program based on physical exercise and health education on MS and health-related quality of life (QoL) in postmenopausal women with BC under AIs. Methods: A total of 56 postmenopausal women, diagnosed with BC, aged 60 years or older (mean age 67.2 years) and on hormonal treatment with AIs, were included in the multimodal physical exercise and health education program, and evaluated before and after their participation. The assessment of the five criteria of the MS included the following: waist circumference, high blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Two main instruments were used to evaluate the impact of the intervention on QoL: the EORTC QLQ C30 (questionnaire for cancers in general) and the EORTC QLQ BR23 (specifically for breast cancer patients). The EuroQol 5D (EQ-5D) was also used to compare these results. Results: The percentage of women meeting the MS criteria was 37.7% at baseline and fell to 15.1% at 3 months after the intervention (p = 0.02). The intervention significantly reduced hypertension (p < 0.001), central obesity (p < 0.001), and the concentration of triglycerides (p = 0.016). No significant changes were observed in fasting glucose and HDL concentration. A statistically significant improvement was found in QoL (on both the QLQ30 and BR23 scales). A multivariate regression model analysis identified marital status (being married) (95% CI: 1.728-131.615, p = 0.014), and percentage of attendance at health education sessions (95% CI: 1.010-1.211, p = 0.029) as positive predictive variables of improvement in MS. Conclusions: The implementation of multimodal, community-based programs of physical exercise and health education improve the prevalence of MS and specific criteria of MS and QoL in postmenopausal women with breast cancer receiving AI treatment.

Abstract 4122948: Lipoprotein(a) associated risk of atherosclerotic cardiovascular disease is independent of C-reactive protein

Background: Elevated lipoprotein(a), present in 1 in 5 individuals, is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Recent studies have reached contrasting conclusions on whether low-grade inflammation measured by elevated C-reactive protein (CRP) modifies the risk of ASCVD from high lipoprotein(a). We tested the hypothesis that high lipoprotein(a) associates with risk of recurrent ASCVD irrespective of elevated or low CRP. Additionally, we performed meta-analyses of previous studies on lipoprotein(a)-associated ASCVD risk stratified by CRP levels and by incident or recurrent events. Methods: We included 3,543 individuals with prevalent ASCVD from the Copenhagen General Population Study (CGPS), a contemporary, prospective Danish cohort study. Hazard ratios (HR) for ASCVD were examined using multivariable adjusted Cox regressions stratified by CRP (&lt;2 mg/L and ≥2 mg/L). Random-effects meta-analyses in primary (incident events) and secondary (recurrent events) prevention were conducted separately, including studies on lipoprotein(a) and risk of ASCVD stratified by CRP. Results: During a median of 7.5 years of follow-up of 3,543 CGPS participants with established ASCVD, 1,425 experienced a recurrent ASCVD event. Multivariable adjusted HRs for ASCVD for high vs. low lipoprotein(a) were 1.41 (95% confidence interval: 1.19-1.67) and 1.31 (1.08-1.59) in individuals with low or elevated CRP with no evidence of effect modification (Figure 1A, p for interaction=0.11). When risk estimates for ASCVD were summarized in separate meta-analyses for primary and secondary prevention settings, a 50 mg/dL higher lipoprotein(a) was robustly associated with increased risk of ASCVD irrespective of CRP levels (Figure 1B). In primary prevention, a 50 mg/dL higher lipoprotein(a) associated with similar summary HRs of 1.18 (1.15-1.20) in low CRP vs. 1.16 (1.14-1.19) in elevated CRP, and likewise in secondary prevention settings, with similar HRs of 1.10 (1.07-1.14) and 1.14 (1.10-1.17), respectively. Conclusion: High lipoprotein(a) was associated with increased risk of ASCVD irrespective of CRP levels both in primary and secondary prevention settings.

Abstract 4136975: Lipoprotein (a) Discovery Project: Assessing Patient and Professional Education Needs

Introduction: It is estimated that 1 in 5 Americans have high lipoprotein (a) [Lp(a)] levels. High levels of Lp(a) are an independent, predominantly inherited, and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). More investigation is needed to better understand the gaps in both professional and patient education on Lp(a) and its associated risk with ASCVD. Goals: The American Heart Association (AHA) is implementing a national 3-year initiative called the Lp(a) Discovery Project to understand system-level practice patterns for patients screened for high Lp(a) and develop models for national education. We aim to gauge an understanding of healthcare professional (HCP) and patient awareness, perceptions, knowledge, and behaviors of Lp(a) to develop a comprehensive educational approach that ultimately encourages patient-provider shared decision-making. Methods: To assess patient education needs, an online survey was conducted from October 11 to November 6, 2023, by Harris Insights&amp;Analytics LLC with a nationally representative sample of 3,006 U.S. adults 18 years+. To assess professional education needs, the AHA engaged 10 champions from diverse health systems with established Lp(a) screening processes and workflows to participate in a Learning Healthcare System model to share best practices, inform on models for Lp(a) screening, and provide input on professional education topics. Results: The patient survey revealed that 34% of adults do not perceive high Lp(a) to pose an increased risk of heart attack, peripheral artery disease or stroke. If told that high Lp(a) does increase this risk, 63% are motivated to have their Lp(a) level checked and 88% would be motivated to reduce their risk for these conditions if they had high Lp(a). Ultimately, HCP recommendation was the most significant driver in getting screened among those who had their Lp(a) measured (61%). AHA-led champion interviews revealed that primary and specialty care HCPs need education on the importance of Lp(a) testing and cascade screening for family members as well as care considerations for patients with high Lp(a). Conclusion: Given that patients are most likely to be screened for Lp(a) if their HCP recommends it, we will focus on 1) educating patients and HCPs on the connection between Lp(a) and risk for cardiovascular disease and stroke and 2) providing HCPs with guidance on care considerations for those with high Lp(a) including cascade screening.

Correlation study between lipid profile parameters and liver function enzymes in Babylon province

Objective: The present study was an observational case control design. The data of study were collected in the period from first of January 2024 to March 2024. The study was conducted from clinical Laboratory private in Hilla City, Babylon province, Iraq. Material and methods: A total number of subjects involved in this study was 150 patients, from both sex (male and female) with age range (5-85). Blood samples were taken from each one to determination lipid profile tests (total cholesterol, total triglyceride, High and Low-density lipoprotein cholesterol and liver function tests (ALT, AST, ALP, TSB) and investigation the correlation between them. Results: The results showed that, these were significant correlation between these tests according to male groups, the strength and direction of the correlation between TC and TG levels. The value being significant suggests that there was a moderate strong relationship between these variables (0.491). A strong positive correlation between TC and LDL levels (0.799), HDL and ALP levels (0.290), ALT and AST levels (0.777). In addition, a positive association between AST and ALP levels (0.125), TC and LDL levels (0.799). On the other hand, a weak negative association TC and AST levels (0.045), TC and TSB levels (-0.185), TG and HDL levels (-0.04). TG and AST levels (-0.065), TG and TSB levels (-0.184), HDL and ALT levels (0.123), HDL and AST levels (-0.133), ALT and TSB levels (-0.08) and between ALP and TSB levels (-0.08). However, a moderate negative association between TG and LDL levels (-0.32) and a very weak negative association between HDL and TSB (-0.016). Conclusion: In male group, a strong positive correlation between TC and LDL levels, HDL and ALP levels, ALT and AST levels. A positive association between AST and ALP levels, TC and LDL levels, these were significant correlation between these tests according to female groups, the strength and direction of the correlation between TC and TG levels, a moderate strong relationship between these variables, TC and LDL levels, ALT and AST levels, ALT and ALP levels, ALT and TSB levels, AST and ALP levels, AST and TSB levels and ALP and TSB levels. And moderately strong negative correlation between HDL and ALT levels. So, a relatively weak positive correlation between LDL and AST levels in female group. Moderately positive correlation between LDL and ALP levels and between LDL and TSB levels.

Remnant cholesterol and cardiovascular and all-cause mortality in Korean adults

Abstract Background Although previous studies have reported that remnant cholesterol (RC) is associated with cardiovascular disease, studies on RC and various mortality related outcomes including cardiovascular mortality in the general population are scarce and most of them are limited to Western populations. Purpose This study aims to evaluate the effect of RC on mortality related outcomes in a relatively young and middle-aged Korean population. Methods This cohort study included 268,219 subjects (mean age, 38 years and 50.6% men) who were enrolled in the Kangbuk Samsung Health Study between 2003 and 2016. Fasting RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDLC). Results The median RC was 0.47 mmol/L (18 mg/dL) and the prevalence of ≥ 1 mmol/L RC was 11.4%. During the median FU of 6.7 years, high RC (RC ≥ 0.47 mmol/L) significantly increased the risk of multivariable-adjusted cardiovascular mortality compared with low RC (HR[95% CI], 1.43[1.07, 1/93]). Compared with the lowest quintile (RC &amp;lt;0.31 mmol/L), the HRs for cardiovascular mortality were 1.95[0.78, 4.84], 2.47[1.03, 5.91], 2.39[1.00, 5.72], and 2.84[1.19, 6.78] in the second, third, fourth, and highest quintiles, respectively. The HRs for all-cause mortality in the 3rd, 4th, and highest quintiles remained significant (1.24[0.97, 1.59], 1.38[1.08, 1.76], 1.34[1.05, 1/71], and 1.32[1.03, 1.69] in the 2nd, 3rd, 4th, and highest quintiles, respectively). However, there was no significant risk for cancer mortality between RC quintiles. Notably, subgroup analysis showed that individuals with high RC and high hsCRP and high RC and high lipoprotein(a) had a more than twofold and threefold increased risk of cardiovascular mortality, respectively, compared with low RC and low hsCRP and low RC and low lipoprotein(a). Conclusions High RC was significantly associated with increased risk of cardiovascular and all-cause mortality, but not with cancer mortality. In particular, high hsCRP and high lipoprotein(a) weighted the risk association between high RC and cardiovascular mortality.

Lipoprotein(a) cardiovascular disease risk not captured by low density lipoprotein cholesterol and apolipoprotein B

Abstract Background Elevated lipoprotein(a) affects 1 in 5 individuals and is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis (AVS). However, lipoprotein(a) measurements are not widely implemented in clinical practice. Low-density lipoprotein (LDL) cholesterol and apolipoprotein B (ApoB) measurements include contributions from lipoprotein(a), yet whether these measurements can replace measurements of lipoprotein(a) in assessing cardiovascular disease risk from this causal risk factor is unknown. Purpose We tested the hypotheses that lipoprotein(a) risk of ASCVD and AVS is captured by LDL cholesterol or ApoB. Methods We included 70,189 individuals from a prospective contemporary cohort study of the general population. Mediated risk by LDL cholesterol and ApoB in the association between lipoprotein(a) and risk of ASCVD and AVS was examined using four-way decomposition analyses stratified by statin treatment at baseline. Results During a median follow-up of 10.8 years, 7,127 developed ASCVD and 1,516 AVS. Per 50 mg/dL higher lipoprotein(a), multivariable adjusted hazard ratios were 1.22 (95% CI: 1.18-1.26) for ASCVD and 1.36 (1.28-1.46) for AVS. In individuals without statin use, LDL cholesterol mediated 19% (15%-24%) of the risk of ASCVD from lipoprotein(a) and 7.7% (1.5%-14%) of the risk of AVS from lipoprotein(a) (Figure 1). Corresponding values for ApoB were 14.0% (11%-18%) and 6.6% (2.8%-10%). In statin users (n=9,570), LDL cholesterol did not mediate risk of ASCVD from lipoprotein(a) but mediated 8.0% (0.8%-15%) of the risk of AVS from lipoprotein(a). Correspondingly, ApoB mediated 9.8% (2.2%-17%) of the risk of ASCVD and 4.2% (0.4%-8.0%) of the risk of AVS from lipoprotein(a). Conclusion Lipoprotein(a) risk of ASCVD and AVS is not adequately captured by LDL cholesterol and ApoB. Therefore, lipoprotein(a) measurement is needed in all individuals to capture the cardiovascular disease risk from this causal risk factor.

Coronary atherosclerotic plaque burden and characterization by spectral computed tomography scan in patients with high lipoprotein a and non-hemodynamically significant stenosis

Abstract Introduction Atherosclerotic coronary disease increases morbidity and mortality worldwide. Lipoprotein A (LpA) has emerged as a cardiovascular risk marker, but little is known of its direct influence in plaque volume and composition. Spectral computed tomography (CT) technology allows to characterize coronary plaques with new promising tools. Purpose To evaluate the association of LpA with the extent and composition of non-significant coronary plaques producing stenosis &amp;lt;50%. Methods We prospectively recruited 109 patients referred for noninvasive CT angiography (November 2023-January 2024) with suspected coronary artery disease. 20 had totally/partially non-calcified, non-significant coronary plaques. Plaques were segmented and volume was measured. Their composition was stablished as calcified (&amp;gt;200 UH), lipidic (&amp;lt;60 UH) and fibrous (60-200 UH). Spectral data-based plaque parameters were analyzed, including radiological attenuation on polyenergetic images (CTPI), on virtual low/high monoenergetic images (CT40KeV and CT140KeV, respectively), variation in attenuation across monoenergetic levels (slope40-140 KeV) and Z-effective value. CT scan images were acquired with a 128 detectors dual-layer spectral scan with prospective-retrospective/synchronization. Intravascular iodine-based contrast was administered. LpA was stablished as high (≥25 mg/dL) or low (&amp;lt;25 mg/dL). Results Mean age was 60 ± 11. Cardiovascular risk factor were equally distributed between groups. We analyzed 33 plaques. Total plaque volume was significantly higher in high LpA patients (125.9 mm3 vs 62.1 mm3). There were no differences in plaque composition by LpA (Table). Additionally, spectral data showed significantly higher plaque attenuation on CT140KeV images in high LpA patients (36.07 vs 21.32 HU; p = 0.05). There were no differences for the rest of spectral parameters. Conclusions Plaque volume was higher in patients with non-significant atherosclerotic disease and high LpA, but these plaques showed similar composition in high and low LpA patients. These patients might, therefore, respond to the same conventional treatment event though there is not specific treatment for high LpA yet. Additionally, spectral CT140KeV images could add more precision differentiating these plaques since radiological attenuation in these reconstructions is higher in patients with high LpA.TableFigure

Does the LPA genotype have a role in coronary artery disease risk beyond Lp(a) values?

Abstract Introduction High lipoprotein(a) [Lp(a)] concentrations are one of the most important genetically determined risk factors for coronary artery disease (CAD). Many functional single nucleotide polymorphisms (SNPs) of the LPA gene have pronounced effects on Lp(a) concentrations. Studies show that rs3798220 polymorphism is strongly associated with Lp(a) concentration and also with risk of CAD. Goal: To evaluate if LPA rs3798220 T&amp;gt;C is associated with CAD beyond its effect on Lp(a) levels. Methods We performed a case-control study with 3,157 individuals (1,721 CAD patents and 1,436 controls). The LPA rs3798220 T&amp;gt;C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). This variant has a minor allele frequency (MAF) &amp;lt;2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Laboratory analysis was performed, and Lp(a) biochemical levels were measured in the cases and controls. Chi-squared tests were used to determine differences by genotype in CAD association (in cases and controls). We also reported a multivariate logistic regression to test if this LPA variant is still independently associated with CAD after adjustment to Lp(a) levels and traditional risk factors for CAD. Results Wild-type genotype TT was increased in the group without CAD, whereas the genotype TC was higher in patients with CAD (p&amp;lt;0.0001). After multivariate logistic regression, adjusted for traditional risk factors, the TC genotype remained in the equation as an independent risk factor for CAD (OR=2.36; 95%CI: 1.54–3.61; p&amp;lt;0.0001). When the multivariate regression analysis is adjusted for traditional risk factors plus Lp(a) levels, the TC genotype remains in the equation as independently associated with CAD despite being substantially attenuated (OR=1.67; 95%CI: 1.07–2.60; p=0.025). Conclusion LPA rs3798220 T&amp;gt;C may be an independent risk factor for CAD beyond the effect of rising Lp(a) levels. Perhaps testing for the genetic determinants of Lp(a) relative to direct measurement of Lp(a) level could provide additional prognostic utility.

Impact of High Lipoprotein(a) Levels on Delayed Wound Healing in Patients With Chronic Limb-Threatening Ischemia After Peripheral Endovascular Therapy.

Elevated lipoprotein(a) [Lp(a)] levels are a causal risk factor for peripheral artery disease. However, data on their effect on delayed wound healing in patients with chronic limb-threatening ischemia (CLTI) are limited. The present study assessed the association between elevated Lp(a) levels and delayed wound healing in patients with CLTI. This study included 280 patients who successfully received endovascular therapy for CLTI between September 2016 and August 2021. High Lp(a) levels were defined as those >30 mg/dL. The primary outcome was wound healing. During a median follow-up of 20.4 months (interquartile range 6.8-38.6 months), 146 patients achieved wound healing. The wound healing rate at 24 months was significantly lower in the high Lp(a) than low Lp(a) group (41.1% vs. 86.3%, respectively; P<0.001). The adjusted risk ratio was 0.19 (95% confidence interval 0.13-0.29, P<0.001). Lp(a) levels of 31-50 and >50 mg/dL, but not 16-30 mg/dL, were significantly associated with delayed wound healing relative to Lp(a) levels of ≤15 mg/dL. Elevated Lp(a) levels were independently associated with delayed wound healing in patients with CLTI treated with endovascular therapy.

Molecular mechanism of ectopic lipid accumulation induced by methylglyoxal via activation of the NRF2/PI3K/AKT pathway implicates renal lipotoxicity caused by diabetes mellitus.

Patients with chronic kidney disease (CKD) have a high incidence of dyslipidemia comprising high triglyceride (TG) and low high-density lipoprotein (HDL)-cholesterol levels. An abnormal increase of TGs within cells can lead to intracellular lipid accumulation. In addition to dyslipidemia, hyperglycemia in diabetes may elicit ectopic lipid deposition in non-adipose tissues. Hyperglycemia increases intracellular levels of methylglyoxal (MG) leading to cellular dysfunction. A deficit of glyoxalase I (GLO1) contributes to dicarbonyl stress. Whether dicarbonyl stress induced by MG causes renal lipotoxicity through alteration of lipid metabolism signaling is still unknown. In this study, mice with high fat diet-induced diabetes were used to investigate the renal pathology induced by MG. NRK52E cells treated with MG were further used in vitro to delineate the involvement of lipogenic signaling. After treatment with MG for 12 weeks, plasma TG levels, renal fatty changes, and tubular injuries were aggravated in diabetic mice. In NRK52E cells, MG activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and sterol regulatory element-binding protein 1 (SREBP1), resulting in stimulation of fatty acid synthase. The intracellular accumulation of lipid droplets was mainly contributed by TGs, which increased the oxidative stress accompanied by high Nrf2 expression. In addition, MG time-dependently activated cyclin D, cyclin-dependent kinase 4 (CDK4), and cleaved caspase-3, evidencing that G0/G1 arrest was associated with apoptosis of NRK52E cells. In conclusion, our studies revealed the mechanism of lipotoxicity caused by MG. The target of such dicarbonyl stress may become a promising therapy for diabetic CKD.

High Lipoprotein(a) as a Cause of Kidney Disease: A Population-Based Mendelian Randomization Study

High Lipoprotein(a) as a Cause of Kidney Disease: A Population-Based Mendelian Randomization Study

Apolipoproteins, lipids, lipid-lowering drugs and risk of amyotrophic lateral sclerosis and frontotemporal dementia: a meta-analysis and Mendelian randomisation study.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have clinical, pathological and genetic overlapping. Lipid pathways are implicated in ALS. This study examined the effect of blood lipid levels on ALS, FTD risk, and survival in ALS. A systematic review and meta-analysis of high and low-density lipoprotein cholesterol (HDL-c and LDL-c), total cholesterol, triglycerides, apolipoproteins B and A1 levels with ALS was performed. Two-sample Mendelian randomisation (MR) analysis sought the causal effects of these exposures on ALS, FTD, and survival in ALS. The effect of lipid-lowering drugs was also examined using genetic proxies for targets of lipid-lowering medications. Three cohort studies met the inclusion criteria for meta-analysis. Meta-analysis indicated an association between higher LDL-c (HRper mmol/L = 1.07, 95%CI:1.02-1.12; =18%) and lower HDL-c (HRper mmol/L = 0.83, 95%CI:0.74-0.94; =0%) with an increased risk of ALS. MR suggested causal effects of higher LDL-c (ORIVW = 1.085, 95%:CI 1.008-1.168, pFDR = 0.0406), total cholesterol (ORIVW = 1.081, 95%:CI 1.013-1.154, pFDR = 0.0458) and apolipoprotein B (ORIVW = 1.104, 95%:CI 1.041-1.171, pFDR = 0.0061) increasing ALS risk, and higher apolipoprotein B level increasing FTD risk (ORIVW = 1.424, 95%CI 1.072-1.829, pFDR = 0.0382). Reducing LDL-c through APOB inhibition was associated with lower ALS (ORIVW = 0.84, 95%CI 0.759-0.929, pFDR = 0.00275) and FTD risk (ORIVW = 0.581, 95%CI 0.387-0.874, pFDR = 0.0362). These data support the influence of LDL-c and total cholesterol on ALS risk and apolipoprotein B on the risk of ALS and FTD. Potential APOB inhibition might decrease the risk of sporadic ALS and FTD. Further work in monogenic forms of ALS and FTD is necessary to determine whether blood lipids influence penetrance and phenotype.

TCT-15 Impact of High Lipoprotein(a) Levels on 5-Year Clinical Outcomes Following Percutaneous Coronary Intervention With Drug-Eluting Stent in Korean Population

TCT-15 Impact of High Lipoprotein(a) Levels on 5-Year Clinical Outcomes Following Percutaneous Coronary Intervention With Drug-Eluting Stent in Korean Population

Prevalence of metabolic syndrome among adults treated at a district hospital outpatient department.

Metabolic syndrome (MetS) is a collection of risk factors, including hypertension, high fasting blood glucose, high fasting triglyceride and low high-density lipoprotein (HDL) cholesterol levels that may increase the risk for cardiovascular disease and type 2 diabetes. The study aimed to determine the prevalence of MetS among adults attending a Free State district hospital's outpatient department. A cross-sectional study included a consecutive sample of consenting patients 18 years and older from 18 October 2021 to 19 November 2021. Patients' waist circumference was measured, and data were extracted from patients' files. The 409 participants were predominantly females (64.2%). The median age was 60 years. Triglyceride and HDL cholesterol levels were available for 27.4% and 26.9% of patients, respectively. Of the 278 (68.0%) patients with sufficient information to determine their MetS status, 187 (67.3%) had MetS. Of the males with sufficient information, 49.1% (n= 56/114) had MetS compared to 79.9% (n= 131/164) of the females with sufficient information (p 0.001). The age group 60-79 years had the highest prevalence (76.7%,p 0.001). In all race groups, at least two-thirds of patients had MetS (p= 0.831). Incomplete patient notes and failure to do investigations led to a third of patients not having sufficient information to determine their MetS status. In patients with sufficient information, a high prevalence of MetS was found.Contribution:This study highlights the challenges of determining MetS retrospectively in an outpatient population and the need for completeness of medical note keeping and routine investigations in high-risk patients. It also notes the high prevalence of MetS.

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

Background and aimsRecent 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. MethodsWe 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. ResultsDuring 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. ConclusionsAll 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.

High lipoprotein(a) is a risk factor for peripheral artery disease, abdominal aortic aneurysms, and major adverse limb events.

To summarize evidence from recent studies of high lipoprotein(a) as a risk factor for peripheral artery disease (PAD), abdominal aortic aneurysms (AAA), and major adverse limb events (MALE). Additionally, provide clinicians with 10-year absolute risk charts enabling risk prediction of PAD and AAA by lipoprotein(a) levels and conventional risk factors. Numerous studies support high lipoprotein(a) as an independent risk factor for PAD, AAA, and MALE. The strongest evidence is from the Copenhagen General Population Study (CGPS) and the UK Biobank, two large general population-based cohorts. In the CGPS, a 50 mg/dl higher genetically determined lipoprotein(a) associated with hazard ratios of 1.39 (1.24-1.56) for PAD and 1.21 (1.01-1.44) for AAA. Corresponding hazard ratio in the UK Biobank were 1.38 (1.30-1.46) and 1.42 (1.28-1.59). In CGPS participants with levels at least 99th (≥143 mg/dl) vs, less than 50th percentile (≤9 mg/dl), hazard ratios were 2.99 (2.09-4.30) for PAD and 2.22 (1.21-4.07) for AAA, with a corresponding incidence rate ratio for MALE of 3.04 (1.55-5.98) in participants with PAD. Evidence from both observational and genetic studies support high lipoprotein(a) as a causal risk factor for PAD, AAA, and MALE, and highlight the potential of future lipoprotein(a)-lowering therapy to reduce the substantial morbidity and mortality associated with these diseases.

High-density lipoprotein cholesterol level and risk of muscle strength decline and sarcopenia in older adults

BackgroundRecent studies have demonstrated that very high high-density lipoprotein cholesterol (HDL-C) level was paradoxically linked with higher risk of cardiovascular mortality, all-cause mortality, and several age-related diseases. However, whether very high HDL-C level is associated with a higher risk of sarcopenia in older adults remains unclear. We aimed to investigate the association between HDL-C level and the risk of developing sarcopenia and low grip strength over time in older adults. MethodsParticipants were from the ongoing China Health and Retirement Longitudinal Study (CHARLS), which includes a nationally representative sample of adults aged ≥ 45 years and was performed from 2011 to 2020 with follow-ups every two to three years. The current study included 4031 participants aged ≥60 years. Muscle health related data were collected in wave 2011, 2013, and 2015. Based on HDL-C level at baseline, participants were categorized into five groups: <35 mg/dl, 35-40 mg/dl, 40-60 mg/dl, 60-70 mg/dl and >70 mg/dl. The main outcomes were incident sarcopenia and incident low grip strength over follow-up. Low grip strength and sarcopenia were defined according to the 2019 Consensus by the Asian Working Group for Sarcopenia. Cox proportional-hazard regression was performed to investigate the association between HDL-C level and the risk of developing sarcopenia and low grip strength in older adults. ResultsThe mean age of study sample was 67.3 (SD 6.1) years, and 49.6% were male. During an average 3.7-year follow-up, 409 (10.1%) participants developed sarcopenia and 771 (21.1%) developed low grip strength. Non-linear association was observed between HDL-C level and the hazard of developing sarcopenia and low grip strength. The multivariable model showed that compared to the reference group (40-60 mg/dl), older adults with very high HDL-C level (>70 mg/dl) had a significant higher risk of developing sarcopenia (HR 1.69, 95% CI 1.28 - 2.23) and low grip strength (HR 1.23 95% CI 1.00 - 1.51). Stratified analyses by sex revealed similar association. ConclusionsWe present the first longitudinal evidence that very high HDL-C level was associated with a significant higher risk of muscle strength decline and developing sarcopenia in older adults. It is essential to monitor the muscle health of older adults with very high HDL-C level in clinical practice.

Association between Atherogenic Dyslipidemia and Subclinical Myocardial Injury in the General Population.

Background: Subclinical myocardial injury (SCMI) is associated with an increased risk of poor cardiovascular disease (CVD) outcomes. Understanding the underlying risk factors for SCMI is crucial for the prevention and management of CVD. We hypothesized that atherogenic dyslipidemia, a combination of high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C), is associated with an increased risk of SCMI. Methods: This analysis from the third National Health and Nutrition Examination Survey (NHANES-III) included 7093 participants (age 59.3 ± 13.4 years, 52.8% women, and 49.4% White) free of CVD. Atherogenic dyslipidemia was defined as TG ≥ 150 mg/dL and HDL-C < 40 mg/dL in men or <50 mg/dL in women. A validated electrocardiographic-based cardiac infarction injury score (CIIS) ≥ 10 was considered positive for SCMI. Multivariable logistic regression analysis was used to examine the association of different combinations of TG and HDL-C groups, including atherogenic dyslipidemia with SCMI. Results: About 22.5% (n = 1594) of participants had atherogenic dyslipidemia, and 26.3% (n = 1862) had SCMI. Compared to participants with normal TG and normal HDL-C, those with atherogenic dyslipidemia had a higher prevalence of SCMI (31.2% vs. 23.9%, p-value < 0.001). In a multivariable logistic regression model, atherogenic dyslipidemia was associated with the highest odds of SCMI followed by high TG/normal HDL-C, then low HDL-C/normal TG [OR (95% CI): 131 (1.14, 1.52), 1.13 (0.97, 1.33), and 1.01 (0.86, 1.20), respectively). Conclusions: Atherogenic dyslipidemia is associated with a higher risk of SCMI, which highlights the role of nontraditional risk factors in the development of subclinical CVD.

High lipoprotein(s) as a cause of chronic kidney disease: A population-based Mendelian randomization study

High lipoprotein(s) as a cause of chronic kidney disease: A population-based Mendelian randomization study

Elderly patients with very high plasma lipoprotein(a) concentrations and few cardiovascular consequences: a case series.

Lipoprotein(a) (Lp(a)) is an atherogenic low-density lipoprotein (LDL)-like particle that is currently regarded as a non-modifiable risk factor for atherosclerotic cardiovascular disease. The number of patients detected with elevated Lp(a) concentrations has been increasing in recent years, although the implication of this finding is unclear for patients and physicians. We screened our lipid clinic database for patients aged >65 years with very high Lp(a) concentrations, which were defined as >230 nmol/L, and cardiovascular outcomes were assessed. The patients' (n = 16) mean (±standard deviation) age was 72.2 ± 7.1 years and the mean Lp(a) concentration was 313 ± 68 nmol/L. After a cumulative 129.0 patient-year follow-up (mean: 8.1 ± 4.2 years), the mean age was 80.3 ± 7.0 years. We observed a low baseline prevalence of cardiovascular events, with only two patients having a history of cardiovascular events. Furthermore, zero incident adverse cardiovascular events were recorded over the follow-up. Therefore, very high Lp(a) concentrations and disease-free old age are not mutually exclusive. Our aggregated clinical experience is that there is only a modest association between elevated Lp(a) concentrations and adverse outcomes. Nonetheless, we still advise treating modifiable risk factors in these patients.