High LDL Research Articles

Relationship of Body Fat Distribution and Anthropometric Status with Lipid Profiles in Ethnic Minang Adult Women

Background The prevalence of metabolic syndrome is increasing, and it is a risk factor for cardiovascular disease. One of the indicators of metabolic syndrome is dyslipidemia. Objective This study analyzes adult women's body fat distribution, anthropometric status, and lipid profiles. Methods This study used a cross-sectional design with simple random sampling. A total of 159 adult women aged 25-44 living in the Pesisir Selatan district participated in the study. Ethical approval was obtained, and the respondents were not taking cholesterol-lowering drugs. Body fat distribution, anthropometric status, and lipid profile data were assessed using standard procedures and compared with the categories recommended for Indonesian women. Results The average age of respondents was 36.6 years. 45.3% of the respondents suffered from dyslipidemia. Most of them were obese based on BMI and had central obesity based on WC. Additionally, 76% had an above-normal fat mass. Lipid profile data showed that some (45.3%) had high total cholesterol, 44% had high LDL, 8% had high TG, and a small proportion (15%) had low HDL levels. There was a significant relationship (p < 0.01) between body fat distribution and anthropometric status with lipid profiles, except for total cholesterol (p < 0.05). A negative correlation was found between body fat percentage, BMI, and WC with HDL, while a positive correlation existed between body fat percentage, BMI, and WC with TG and LDL levels. Conclusions Obesity is found to be higher, and dyslipidemia begins to occur in women at a younger age, increasing the risk of metabolic syndrome. Education and routine screening are necessary to prevent non-communicable diseases.

Variants in LPA are associated with Familial Hypercholesterolaemia: whole genome sequencing analysis in the 100,000 Genomes Project

Abstract Background Familial Hypercholesterolaemia (FH) is an inherited disease of high LDL-cholesterol (LDL-C) caused by defects in LDLR, APOB, APOE and PCSK9 genes. A pathogenic variant cannot be found in ∼60% of clinical FH patients. Using whole genome sequencing (WGS) we examined genetic determinants of FH. Methods WGS data generated by the 100,000 Genomes Project (100KGP) included 536 FH patients diagnosed using the FH Simon Broome criteria. Rare variants in known FH genes were analysed. Genome-wide association study (GWAS) between 443 FH variant-negative unrelated FH cases and 77,275 control participants of the 100KGP was run using high coverage WGS data. Polygenic risk scores for LDL-C (LDL PRS) and lipoprotein(a) (Lp(a) PRS) were computed. Results An FH-causing variant was found in 17.4% of FH cases. GWAS identified the LPA gene locus being significantly associated (p<1x10-8). FH variant-negative participants had higher LDL and Lp(a) PRSs in comparison to the controls (p<1.0×10-16 and p<4.09×10-6, respectively). Similar associations were found in the monogenic FH with both LDL and Lp(a) PRSs being higher than in controls (p<4.03×10-4 and p<3.01x10-3, respectively). High LDL PRS was observed in 36.4% of FH variant-negative cases, whereas high Lp(a) PRS in 18.5%, with 7.0% having both high LDL and Lp(a) PRSs. Conclusions This genome-wide analysis of monogenic and polygenic FH causes confirms a complex and heterogenous architecture of hypercholesterolaemia, with the LPA gene playing a significant role. Both Lp(a) and LDL-C should be measured for precision FH diagnosis. Specific therapies to lower Lp(a) should be targeted to those who will benefit most.

Association of Risk Factors of Acute Myocardial Infarction and Heart Blockage Among non-diabetic Patients in a Tertiary Care Hospital – An Observational Study

Introduction: Cardiovascular diseases (CVDs) are a leading cause of death in the world. In 2015, an estimated 442.7 million prevalent cases of CVD were present worldwide. Cardiovascular diseases account for more than 17 million deaths globally each year. Previous studies identified diabetes mellitus, hypertension, hypercholesterolemia, smoking, alcohol consumption, obesity and sedentary lifestyle as risk factors. Aim of the study: The aim of this study was to determine the risk factors for acute myocardial infarction associated with heart blockage among non-diabetic patients. Methods: This was an observational study conducted in the Department of Cardiology of Jashore Medical College Sadar Hospital, Jashore, Bangladesh during the period from April, 2021 to March, 2022. In this study, we included 120 non-diabetic patients who were diagnosed with myocardial infarction. Result: Mean age was 53.03±11.3 years & most of our patients were male. Among all patients, majority (65%) patients had >60% blockage, followed by 30(25%) patients had 40%-60% artery blockage, and <40% blockage was found in 10% patients. Hypertension, dyslipidemia & dyslipidemia with hypertension, age ≥60 years, family history of CHD, smoking, diabetes & obesity were individual risk factors of CHD among non-diabetic patients. The most common risk factors for heart blockage were age >45 years, high blood pressure, high LDL, unhealthy diet, and stressful life. Conclusion: In our study, we found hypertension, history of CHD, dyslipidemia, dyslipidemia with hypertension, stress, age ≥60 years, and obesity were individual risk factors for CHD. These elements work as crucial risk factors for myocardial infarction in non-diabetic patients. Risk factors like age >45 years, high blood pressure, high LDL, unhealthy diet, and stressful life were responsible for the highest heart blockage in myocardial infarction patients. J Inv Clin Cardiol 2023; 5(2): 38-44

Interactive effects of outdoor fine particulate matter and metabolic, behavioural, and psychosocial risk factors on cardiovascular disease: analysis of the PURE-China cohort study

Abstract Background Long-term PM2.5 exposure has been associated with an elevated risk of cardiovascular disease (CVD) and its associated risk factors.[1–4] There is a paucity of studies investigating the interactive effects of PM2.5 exposure and a comprehensive list of risk factors including metabolic, behavioural, and psychosocial risk factors on CVD risk.[5] Purpose This study aims to examine the interactive effects of PM2.5 exposure and metabolic, behavioural, and psychosocial risk factors on incident CVD. Methods The Prospective Urban Rural Epidemiology (PURE)-China cohort study is a population-based cohort study recruiting participants aged 35–70 years from 115 communities in 12 provinces of China between 2005 and 2009, and followed up until August 31, 2021.[6] Participants’ metabolic, behavioural, and psychosocial risk factor information was recorded. PM2.5 concentrations were extracted from a 1x1 km2 global model.[7,8] For this analysis, we included participants aged 35–70 years at baseline without a history of CVD, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (CVD deaths, myocardial infarction, stroke, and heart failure). Additive interaction was measured by relative excess risk due to interaction (RERI), the proportion of disease attributable to interaction (AP), and the synergy index (SI).[9,10] To comply with the additive interaction method, we classified concentrations of PM2.5 into low and high levels by the median of 3-year average PM2.5 concentration (45.7 μg/m3, IQR: 33.7-74). Cox proportional hazard models were used to assess the associations of metabolic, behavioural, and psychosocial risk factors on incident CVD by PM2.5 concentrations. Results The PURE-China study recruited 47 931 participants, of which 39 329 are eligible for this analysis. During the median follow-up period of 11.9 years (IQR: 9.6-12.6), 1462 and 2155 major CVD events had occurred in the low and high PM2.5 group respectively. There was a synergistic interaction between PM2.5 and the systolic blood pressure (SBP) for CVD: RERI: 0.363, 95% CI: 0.196-0.531; AP: 0.098, 95% CI: 0.081-0.115; SI: 1.155, 95% CI: 1.132-1.177; high LDL cholesterol: RERI: 0.219, 0.003-0.436; AP: 0.135, 0.008-0.263; SI: 1.549, 0.947-2.533. A significant synergistic interaction was also identified between PM2.5 and household air pollution (RERI: 0.457, 0.292-0.622; AP: 0.277, 0.184-0.37; SI: 3.362, 1.409-8.019). Interactions between PM2.5 and low grip strength on CVD were significantly synergistic, but antagonistic between PM2.5 and low physical activity (RERI: -0.248, -0.485--0.012; AP: -0.174, -0.349-0.001; SI: 0.633, 0.412-0.971). Conclusion Addictive interaction was between PM2.5 and SBP, high LDL cholesterol, household air pollution, low grip strength and low physical activity on incident CVD, indicating the benefit of coordinated control strategies for metabolic, physical, and environmental risk factors for the prevention of CVD.

Low Lung Function Is Associated with High Population Attributable Fraction for Cardiovascular Mortality.

Chronic lung diseases are associated with increased risk of mortality due to coronary heart disease (CHD). Nonetheless, the population attributable fraction (PAF) of lung function impairment relative to other established cardiovascular risk factors is unclear. To evaluate the PAF of low lung function for CHD mortality Methods: We harmonized and pooled lung function and clinical data across 8 US general population cohorts. Impaired lung function was defined as FEV1 and/or FVC ≤95% predicted on baseline spirometry. The association between CHD mortality and risk factors was assessed using cause-specific proportional hazards and Fine-Gray proportional subdistribution hazards models, treating non-CHD mortality as a competing risk. Models were adjusted for lung function as well as age, sex, race/ethnicity, educational attainment, body mass index, smoking status, pack-years of smoking, diabetes mellitus, HDL, and high LDL (≥130 mg/dl). PAF was calculated as the relative change in the average absolute risk of ten-year CHD mortality by elimination of lung function lower than 95% predicted. Among 35143 participants, 1844 of 13174 (14.0%) deaths were due to CHD. Compared to FEV1pp >95%, the sub-distribution adjusted hazards ratio (95%CI) for low FEV1pp was 1.30 (1.18-1.44). The PAF for FEV1pp≤95% was 12%, ranking low FEV1 third in the list of PAF for CHD mortality, after hypertension and diabetes. Low FEV1pp ranked second in the subgroup of active smokers (PAF 14%), after hypertension. Low lung function, even in the range considered clinically normal, ranks high in the list of attributable risk factors for CHD mortality and should be considered in cardiovascular risk stratification.

Burden of cardiovascular disease attributable to metabolic risks in 204 countries and territories from 1990 to 2021.

To evaluate the global cardiovascular disease (CVD) burden attributable to metabolic risks in 204 countries and territories from 1990 to 2021. Following the methodologies used in the Global Burden of Disease Study 2021, this study analyzed CVD deaths and disability-adjusted life-years (DALYs) attributable to metabolic risks by location, age, sex, and socio-demographic index (SDI). In 2021, metabolic risks accounted for 13.59 million CVD deaths (95% UI 12.01 to 15.13) and 287.17 million CVD DALYs (95% UI 254.92 to 316.32) globally, marking increases of 63.3% and 55.5% since 1990, respectively. Despite these increases, age-standardised mortality and DALY rates have significantly declined. The highest age-standardised rates of metabolic risks-attributable CVD mortality and DALYs were observed in Central Asia and Eastern Europe, while the lowest rates were found in High-income Asia Pacific, Australasia, and Western Europe, all of which are high SDI regions. Among the metabolic risks, high systolic blood pressure emerged as the predominant factor, contributing to the highest numbers of CVD deaths [10.38 million (95% UI 8.78 to 12.03)] and DALYs [14.52 million (95% UI 180.42 to 247.57)] in 2021, followed by high LDL cholesterol. Our study highlights the persistent and significant impact of metabolic risks on the global CVD burden from 1990 to 2021, emphasizing the need of designing public health strategies that align with regional healthcare capacities and demographic differences to effectively reduce these effects through enhanced international collaboration and specific policies.

Gender-specific associations between sleep stages and cardiovascular risk factors.

Sleep characteristics are associated with cardiovascular disease (CVD) risk and both sleep and CVD risk vary by gender. Our objective was to examine associations between polysomnographic sleep characteristics and CVD risk after excluding moderate-severe sleep apnea, and whether gender modifies these associations. This was a cross-sectional study with at-home polysomnography in adults in Brazil (n= 1,102 participants with apnea-hypopnea index (AHI)<15 events/hour). Primary exposures were N3, REM, wake after sleep onset (WASO), arousal index (AI) and AHI, and outcomes were blood pressure (BP) and lipid levels. Associations between sleep and BP varied by gender. In women, more N3 was associated with lower systolic BP (-0.40 mmHg per 10 minutes, 95%CI -0.71, -0.09), lower diastolic BP (-0.29 mmHg per 10 minutes, 95%CI -0.50, -0.07), and lower odds of hypertension (OR 0.94, 95%CI 0.89, 0.98). In men, more WASO was associated with higher systolic BP (0.41 mmHg per 10 minutes, 95%CI 0.08, 0.74) and higher odds of hypertension (OR 1.07, 95%CI 1.01, 1.14). No interactions by gender were observed for lipids. More WASO was associated with lower total cholesterol (-0.71 per 10 minutes, 95%CI -1.37, -0.05). Higher AHI was associated with higher total cholesterol (+0.97 per event/hour, 95%CI 0.24, 1.70) and higher LDL (+0.84 per event/hour, 95%CI 0.04, 1.64). N3 is more strongly associated with BP in women, which is consistent with other studies demonstrating gender differences in BP control and CVD risk and adds a novel risk factor. Longitudinal and interventional studies are required to determine whether changes in N3 result in BP changes.

8702 Age-Sex Differences in Global Burden of Ischemic Heart Disease Attributable to High LDL in the Last 3 Decades:Global, Regional, National Variations, Age Dynamics, and Implications for Global Health

Abstract Disclosure: V. Adedara: None. K. Maddineni: None. A. Dekhne: None. M. Chinthapalli: None. G. Potluri: None. A. Parisapogu: None. K. Markandu: None. H. Desai: None. Background: Ischemic Heart Disease (IHD) stands as the foremost cause of mortality globally, contributing to 9.6 million deaths. Elevated levels of low-density lipoprotein cholesterol (LDL-C) consistently feature among the risk factors associated with IHD. Methods: Employing the Global Burden of Disease framework, we computed mortality and DALYs linked to IHD attributable to LDL-C, stratified by age-sex, year, and covering 204 countries and territories during the period from 1990 to 2019. Non-fatal health outcomes were estimated using DISMOD MR 2.1, Bayesian meta-regression tool for epidemiological modelling. Results were expressed in absolute counts and age-standardized rates (ASR) per 100,000 person-years. Results: The total number of deaths attributed to IHD due to elevated LDL-C increased from 2.5 million (95% Uncertainty Interval: 2-3.1 million) in 1990 to 3.7 million (95% UI: 2.8-4.8 million) in 2019. Concurrently, DALYs increased from 60.4 million (95% UI: 50.4-70.7 million) in 1990 to 84.9 million (95% UI: 69.5-101.3 million) in 2019. In terms of ASR, the annual percentage change (APC) in death rates decreased by 36%, and DALY rates decreased by 32% from 1990 to 2019. Regionally, East Asia exhibited the highest increase in APC in death counts by 191%, followed by Commonwealth Low-Income countries at 164%, and Oceania at 160% during the same period. Conversely, the Commonwealth High-Income region experienced the highest decrease at 41%. Males displayed higher APC in death (48% vs. 44%) and DALYs (42% vs. 38%) compared to females over the last three decades. In terms of ASR, males observed a higher decrease compared to females. In 2019, the age group 80-84 years had the highest number of deaths at 534,079 (264,177-813,898), while DALYs were most pronounced in the 55-59 year age group, reaching 10.6 million (8.9-12.3 million). Conclusion: IHD remains a significant global health challenge, with high LDL-C levels being a crucial modifiable risk factor. Age-sex disparities in the burden of IHD are evident, driven by variations in LDL-C metabolism, hormonal changes, and lifestyle factors. Recognizing and addressing these disparities is essential for developing effective prevention and treatment strategies tailored to different populations and age groups. Presentation: 6/2/2024

A-214 Evaluate LDL-C using NIH equation 2, Friedewald equation, and direct homogeneous measurement

Abstract Background It is essential to accurately assess Low-density lipoprotein cholesterol (LDL-C) levels, a key marker for cardiovascular disease often used for treatment recommendations. The Friedewald equation has been used for many years to calculate plasma LDL-C levels, but it has limitations. Therefore, before implementing the NIH equation, we compared LDL-C results from NIH Equation 2 to the Friedewald formula and then to Atellica direct homogeneous assay LDL-C results. Methods A retrospective study of 1200 randomly selected patients out of 53,258 data points pulled from the laboratory information (LIS) system between November 2021 and October 2023. The study evaluated triglycerides, LDL-C, total cholesterol, and HDL-C measurements. The LDL-C calculated using NIH equation 2 has been set in the LIS as a non-reportable test component since November 1, 2021. The results obtained from NIH equation 2 and Friedewald equation were compared. LDL-C levels were measured using an Atellica direct homogeneous assay for an additional 75 specimens. Deming regression analysis compared measured and calculated LDL-C using both formulae. Results The LDL-C calculated using the Friedewald equation has a mean of 106.1 mg/dL and SD 40.1 mg/dL, while the NIH equation has a mean of 108.5 mg/dL and SD 39.9 mg/dL. The average difference between both equations is 2.5 mg/dL, and there is a significant difference between both calculations using paired t-tests (p-value&amp;lt;0.0001). We first compared the calculated LDL-C derived from the Friedewald formula to the NIH equation 2. The regression analysis equation for the Friedewald formula was y = -2.7 + 1.001 X (r = 0.99). When the Triglyceride values &amp;lt;150 mg/dL (N=879), the average difference is 1.3, and the regression equation is -0.45+1.01X(r=0.99). However, when the Triglyceride value &amp;gt;= 150 mg/dL (N=321), the average bias is 5.4 mg/dL, and the regression equation is -11.2+1.05X(r=0.99). The Friedewald formula was compared to the measured LDL-C in 75 specimens; the regression analysis for the Friedewald formula was y = -19.6 + 1.06 X (r = 0.91, p-value &amp;lt;0.0001). The 75 measured LDL-C results were also compared with the NIH formula. The regression analysis of NIH LDL-C with measured LDL-C was y = -5.6 + 0.981 x (r = 0.90, p-value = 0.0002). Both formulae showed a linear relationship against measured LDL-C. The NIH formula outperformed the Friedewald formula; bias difference -7.8(-6.8%) compared to the Friedwald equation bias -12.9(-12.0%). If the NIH equation had been used during this period, an additional 1,116 patients would have had LDL-C results. This is because the Friedewald equation should not be used if the triglyceride value is above 400 mg/dL. Out of the additional patients, 513 (46%) had a high LDL (&amp;gt;100 mg/dL). Conclusions The NIH formula performed better than the Friedewald formula, with a less negative bias when both calculations were compared to direct homogenous measurement. The average difference between the two formulas showed the lowest value when triglyceride &amp;lt; 150 mg/dL. Moving to NIH equation 2 will benefit our population as we had 2% of our patients in the past two years have triglyceride &amp;gt;400 mg/dL.

Abdominal aorta intima-media thickness in children with hypothyroidism

Hypothyroidism is associated with atherosclerosis, which is attributed mainly to an atherogenic lipid profile. Increased intima-media thickness (IMT) is the first structural change detected in atherosclerosis. This prospective cohort study investigated lipid profile and abdominal aorta IMT in patients newly-diagnosed with hypothyroidism and their change one year post-treatment. It included fifty patients divided into three groups according to their diagnosis: congenital hypothyroidism (CH), Acquired and CH stopped treatment/uncontrolled group. They were subjected to history, auxological, blood pressure, non-fasting lipid profile, and abdominal aorta IMT measurement by abdominal ultrasound. These demonstrated high basal cholesterol, triglycerides, and LDL (259.64 ± 82.06, 193.94 ± 71.54, and 144.70 ± 48.46 mg/dl, respectively) and significant reduction after treatment (216.66 ± 44.60, 165.70 ± 53.58 and 123.26 ± 29.79 mg/dl, respectively). Low basal HDL (47.92 ± 10.08 mg/dl) increased significantly (57.56 ± 7.94 mg/dl) after treatment. Abdominal aorta IMT decreased significantly after treatment and achievement of euthyroidism (1.47 ± 0.49 and 1.33 ± 0.41 mm, respectively). In conclusion, upon treatment of hypothyroidism and achievement of euthyroidism, abdominal aorta IMT, cholesterol, triglycerides, and LDL decreased significantly, and HDL increased. Abdominal aorta IMT measurement is an easy and feasible way for the early detection of atherosclerosis.

Polygenic risk of high LDL cholesterol and ischemic heart disease in the general population

Background and aimsWe tested the association of polygenic risk scores (PRS) for low-density lipoprotein cholesterol (LDL-C) and coronary artery disease (CAD) with LDL-C and risk of ischemic heart disease (IHD) in the Danish general population. MethodsWe included a total of 21,485 individuals from the Copenhagen General Population Study and Copenhagen City Heart Study. For everyone, LDL-PRS and CAD-PRS were calculated, each based on >400,000 variants. We also genotyped four rare variants in LDLR or APOB known to cause familial hypercholesterolemia (FH). ResultsHeterozygous carriers of FH-causing variants in APOB or LDLR had a mean LDL-C of 5.40 and 6.09 mmol/L, respectively, and an odds ratio for IHD of 2.27 (95 % CI 1.43–3.51) when compared to non-carriers. The LDL-PRS explained 13.8 % of the total variation in LDL-C in the cohort. Individuals in the lowest and highest 1 % of LDL-PRS had a mean LDL-C of 2.49 and 4.75 mmol/L, respectively. Compared to those in the middle 20–80 %, those in the lowest and highest 1 % of LDL-PRS had odds ratios for IHD of 0.58 (95 % CI, 0.38–0.88) and 1.83 (95 % CI, 1.33–2.53). The corresponding odds ratios for CAD-PRS were 0.61 (95 % CI, 0.41–0.92) and 2.06 (95 % CI, 1.49–2.85). ConclusionsThe top 1 % of LDL-PRS and CAD-PRS conferred effects on LDL-C and risk of IHD comparable to those seen for carriers of rare FH-causing variants in APOB or LDLR. These results highlight the potential value of implementing such PRS clinically.

Association of Risk Factors of Acute Myocardial Infarction and Heart Blockage among Non-Diabetic Patients in A Tertiary Care Hospital– An Observational Study

Introduction: Cardiovascular diseases (CVDs) are a leading cause of death in the world. In 2015, an estimated 442.7 million prevalent cases of CVD were present worldwide. Cardiovascular diseases account for more than 17 million deaths globally each year. Previous studies identified diabetes mellitus, hypertension, hypercholesterolemia, smoking, alcohol consumption, obesity and sedentary lifestyle as risk factors. Aim of the study: The aim of this study was to determine the risk factors for acute myocardial infarction associated with heart blockage among non-diabetic patients. Materials and Methods: This was an observational study conducted in the Department of Cardiology of Jashore Medical College Sadar Hospital, Jashore, Bangladesh during the period from April, 2021 to March, 2022. In this study, we included 120 non-diabetic patients who were diagnosed with myocardial infarction. Result: Mean agewas 53.03±11.3 years &amp; most of our patients were male. Among all patients, majority (65%) patients had &gt; 60% blockage, followed by 30(25%) patients had 40%-60% artery blockage, and &lt;40% blockage was found in 10% patients. Hypertension, dyslipidemia &amp; dyslipidemia with hypertension, age ­ 60 years, family history of CHD, smoking, diabetes &amp; obesity were individual risk factors of CHD among non-diabetic patients. The most common risk factors for heart blockage were age &gt;45 years, high blood pressure, high LDL, unhealthy diet, and stressful life. Conclusion: In our study, we found hypertension, history of CHD, dyslipidemia, dyslipidemia with hypertension, stress, age ­ 60 years, and obesity were individual risk factors for CHD. These elements work as crucial risk factorsfor myocardial infarction in non-diabetic patients. Risk factors like age &gt;45 years, high blood pressure, high LDL, unhealthy diet, and stressful life were responsible for the highest heart blockage in myocardial infarction patients. Medicine Today 2024, Vol.36 (2): 114-119

Associations of long-term exposure to PM2.5 and its constituents with blood lipids and dyslipidemia in Chinese adults: The CHCN–BTH study

Prior research indicates an association between fine particulate matter (PM2.5) and blood lipids, but fewer studies have explored the constituents of PM2.5. This study investigated the long-term effects of PM2.5 and its constituents on blood lipid levels and dyslipidemia. We used generalized linear mixed models to evaluate the associations of 3-year mean concentrations of PM2.5 and its constituents (BC, NH4+, NO3−, SO42−, OM) with blood lipids and dyslipidemia, followed by stratified, interactive, and sensitive analysis. Out of 29,223 participants, there were positive associations between increased PM2.5 and its constituents with total cholesterol (TC), low-density lipoprotein cholesterol (LDL–C), while a negative association with high-density lipoprotein cholesterol (HDL–C). Notably, BC and OM exhibited the most significant association with HDL–C and LDL–C, each interquartile range (IQR) increment of BC and OM were positively associated with higher LDL–C (Percentage change: 21.17%, 95% CI:19.58%, 22.77%; 23.05%, 95% CI: 21.53%, 24.58%), and lower HDL–C (19.23%, 95% CI: 18.27%, 20.17%; 18.72%, 95% CI: 17.81%, 19.62%), respectively. PM2.5 and its constituents were found to be associated with an elevated risk of dyslipidemia. BC, SO42−, and OM were particularly associated with hypoalphalipoproteinemia and hyperbetalipoproteinemia. Stratified analyses showed that females, individuals residing in rural areas, older adults, those who were overweight or obese, non-smokers, non-drinkers, and regular exercisers displayed higher susceptibility to PM2.5 and its constituents. These findings have significant implications for reducing the harm of air pollution to dyslipidemia.

LDLR variant classification for improved cardiovascular risk prediction in familial hypercholesterolemia

Background and aimsFamilial hypercholesterolemia (FH) is a genetic disorder marked by high LDL cholesterol and an increased premature coronary artery disease (CAD) risk. Current dichotomous classification of LDL receptor gene (LDLR) variants may inadequately capture patient variability in LDL cholesterol levels and CAD risk. This study assessed a novel approach for determining LDLR variant severity using variant-specific LDL cholesterol percentiles. MethodsParticipants of the Dutch FH cascade screening program were screened for 456 LDLR variants. For each LDLR variant carrier, a sex- and age-specific LDL cholesterol percentile was derived from the LDL cholesterol level measured at study entry, i.e. generally from the blood drawn for DNA analysis. These percentiles were used to calculate the mean LDL cholesterol percentile for each variant. Based on the variant-specific LDL cholesterol percentiles, carriers were grouped into the following LDL cholesterol strata: <75th, 75th-88th, 88th-92nd, 92nd-96.5th, 96.5th-98th, and ≥98th percentile. Additionally, variants were categorized into class 1 (LDLR deficient) and non-class 1 (often LDLR defective) variants. CAD risk between carriers in the different LDL cholesterol strata and non-carriers was compared using a Cox proportional hazard model. ResultsOut of 35,067 participants, 12,485 (36 %) LDLR variant carriers (mean age 38.0 ± 20.0 years, 47.7 % male) were identified. Carriers had a 5-fold higher CAD risk compared with non-carriers. Hazard ratios for CAD increased gradually from 2.2 (95%CI 0.97–5.0) to 12.0 (95%CI 5.5–24.8) across the LDL cholesterol strata. A 7.3-fold and 3.9-fold increased CAD risk was observed in carriers of class 1 and non-class 1 LDLR variants, respectively. ConclusionsThis study presents a refined approach for classifying LDLR variants based on their impact on LDL cholesterol levels, allowing for more precise, genotype-specific CAD risk estimation in FH patients compared with traditional methods.

Lipid Profile and Triglyceride-Glucose Index (TyG) Alterations in a Single-Center Cohort of Children Diagnosed with Central Precocious Puberty.

Background: A correlation between plasma lipids and timing of pubertal development has been hypothesized, though lipid influence remains unclear in central precocious puberty (CPP). Aim: To assess any possible alterations in the lipid profile and triglyceride glucose index (TyG) in children diagnosed with CPP. Patients and Methods: Retrospective single-center study conducted on children (aged 6.3 ± 2.1 years) evaluated for the suspicion of CPP. Results: Based on the results of the gonadotropin releasing hormone (GnRH) test, considering 5 IU/L as cut-off of the luteinizing hormone peak, CPP was confirmed in 43 patients (57.3%). Sixteen (37.2%) had a pathologic body mass index (BMI), with 9 (20.9%) being overweight and 7 (16.27%) obese. High total cholesterol was found in 3 patients with CPP (6.97%), high triglycerides were found in 11 patients with CPP (25.58%), high LDL cholesterol was found in 5 patients with CPP (11.62%), low HDL cholesterol was found in 12/43 patients with CPP (27.9%), a pathologic TyG was found in 13/43 patients with CPP (30.23%). No significant association was observed in the lipid profile for patients with or without CPP, except for HDL cholesterol, which was lower in the CPP group (47.1 ± 10.9; p = 0.033). However, the association between serum HDL cholesterol and CPP was not confirmed at the multivariate logistic regression analysis adjusted for patients' sex and age (p = 0.1; OR: 1.035; 95% CI: 0.993-1.078). Conclusion: The overall lipid profile of our pediatric patients diagnosed with CPP did not differ from patients having idiopathic precocious thelarche or normal variants of puberty development.

Cardiovascular outcomes in patients with homozygous familial hypercholesterolaemia on lipoprotein apheresis initiated during childhood: long-term follow-up of an international cohort from two registries

Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disease characterised by extremely high plasma LDL cholesterol from birth, causing atherosclerotic cardiovascular disease at a young age. Lipoprotein apheresis in combination with lipid-lowering drugs effectively reduce LDL cholesterol, but long-term health outcomes of such treatment are unknown. We aimed to investigate the long-term cardiovascular outcomes associated with lipoprotein apheresis initiated in childhood or adolescence. In this cohort study, data were drawn from the HoFH International Clinical Collaboration (HICC) and the international registry for Children with Homozygous Hypercholesterolemia on Lipoprotein Apheresis (CHAIN). An overall cohort included patients diagnosed with HoFH aged 0-18 years who were alive and in follow-up between Jan 1, 2010, and Nov 8, 2021, and whose high plasma LDL cholesterol concentrations made them eligible for lipoprotein apheresis. To compare cardiovascular outcomes, patients who initiated lipoprotein apheresis in childhood (lipoprotein apheresis group) and patients who only received lipid-lowering drugs (pharmacotherapy-only group) were matched by sex and untreated plasma LDL cholesterol concentrations. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischaemic stroke, percutaneous coronary intervention, coronary artery bypass grafting, aortic valve replacement, peripheral artery disease, carotid endarterectomy, angina pectoris, and supra-aortic or aortic stenosis (collectively referred to as atherosclerotic cardiovascular disease), for which survival analyses were performed in the matched cohort. Cox regression analyses were used to compare disease-free survival between cohorts and to calculate hazard ratio (HR) and 95% CI adjusted for sex, age at diagnosis, untreated plasma LDL cholesterol concentration, and number of lipid-lowering therapies other than lipoprotein apheresis. The overall cohort included 404 patients with a median age at diagnosis of 6·0 years (IQR 3·0-9·5) and median untreated plasma LDL cholesterol of 17·8 mmol/L (14·7-20·8). The matched cohorts included 250 patients (125 patients per group), with a median untreated LDL cholesterol of 17·2 mmol/L (14·8-19·7). Mean reduction in plasma LDL cholesterol concentrations between baseline and final follow-up was greater in the lipoprotein apheresis group (-55% [95% CI -60 to -51] vs -31% [-36 to -25]; p<0·0001). Patients in the lipoprotein apheresis group had longer atherosclerotic cardiovascular disease-free survival (adjusted HR 0·52 [95% CI 0·32-0·85]) and longer cardiovascular death-free survival (0·0301 [0·0021-0·4295]). Cardiovascular death was more common in the pharmacotherapy-only group than in the lipoprotein apheresis group (ten [8%] vs one [1%]; p=0·010), whereas median age at coronary artery bypass grafting was lower in the lipoprotein apheresis group than in the pharmacotherapy-only group (15·0 years [IQR 12·0-24·0] vs 30·5 years [19·0-33·8]; p=0·037). Among patients with HoFH, lipoprotein apheresis initiated during childhood and adolescence is associated with reduced long-term risk of atherosclerotic cardiovascular disease and death, and clear benefits of early initiation of high-frequency treatment on reducing plasma cholesterol were found. Consensus recommendations are now needed to guide more widespread and timely use of lipoprotein apheresis for children with HoFH, and research is required to further optimise treatment and ensure benefits of early and aggressive treatment delivery are balanced against effects on quality of life. Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; European Atherosclerosis Society; and the US National Heart, Lung, and Blood Institute, National Institutes of Health.

Lipid profile in patients with acute coronary syndrome undergoing cardiac rehabilitation. Characteristics and effects of the program. The importance of small and dense LDL (LDLpd)

Abstract Funding Acknowledgements None. Introduction Recently it has been shown that not all lipid risk for atherosclerosis is due to LDL cholesterol. Both remnant particles and small and dense LDL (LDLpd) have been associated with a higer risk of the first cardiovascular events and recurrences. Methods We analyzed the lipid profile at admission of patients undergoing a cardiac rehabilitation (CR) program in a tertiary referral hospital, in association with other analytical parameters, clinical characteristics and outcomes of CR in these patients. We collected data from patients who completed the programme between January 2022 and March 2023 on admission and at the end of the programme. Clinical and anthropometric data and the results of the stress tests were collected. We defined a TG/HDL ratio greater than 2 as being associated with the presence of small and dense LDL. Results 170 patients who had complete analytical profiles at hospital admission were included, 80.5% were male with a mean age 57.9+/-9 years, 92.5% were referred after an acute coronary syndrome, 25.6% were diabetic, 56.6% were smokers and 37.7% were obese. LDLpd at hospital admission was present in 73.4% of the patients. Male gender was more likely (86.3 vs. 68.9%, p=0.01, p=0.01) as well as being obese (83.9 vs 68.8%, p=0.04). No differences were found in terms of age, presence of DM, smoking or peripheral arterial disease. Nor did functional capacity or baseline quality of life. Less improvement was found in the SF 36 questionnaire (-6 vs +20, p=0.011), but similar in ergometry. Basal lipid profile was associated with higher total Ch values (173 vs 149, p=0.002), Ch LDL (104 vs 79, p=0.000), remnants (32 vs 14, p=0.000). As for baseline LDL, 51.6% with LDLpd,had it high LDL Ch&amp;gt;100 mg/dl, compared to 22.2% of those without LDLpd (P=0.002). As for the profile at discharge, we found that 63.5% still had LDLpd at discharge from the CR program ( vs. 15.9% of those without elevated LDLpd, P=0.000) and 22% had elevated remnants (P=0.002). After CR, these patients still had higher TG values (128 vs 81, p=0.000), lower HDL-C (44 vs 56, p=0.003) and higher remnants (24 vs 17, p=0.000) despite the fact that a greater decrease in remnants and TG/HDL in this group. Conclusions More than one third of the patients who undergo a Cardiac Rehabilitation Program in our centre have LDLpd. Initially, male and obese patients have higher LDL and remnants. A weaker effect of the CR program in improving the lipidic profile has been observed in those patients. Consideration should be given to enhance lipid-lowering and intensive weight-loss treatments to decrease cardiovascular risk in this population.

From plate to profile: investigating the influence of dietary habits and inactive lifestyle on lipid profile in medical students at clerkship

BackgroundDietary habits have a strong association with body lipid levels and hyperlipidemia increases the risk of cardiovascular and metabolic diseases. Dietary habits have been a major concern among medical students due to busy schedules and demanding tasks. This study was designed to know the dietary habits and lifestyle of medical students and its association with their lipid profile.MethodsWe recruited 120 medical students at clerkship of the age of 18 and above. Weekly dietary habits were evaluated by an 18-item questionnaire. Five ml blood was drawn from the students and lipid profiles were measured at Dow Diagnostic Research and Reference Laboratory (DDRRL). Data was analyzed by SPSS V.22.ResultsWe found 70% of students were not involved in any physical activity throughout the week. Only 15.83% were following a regular diet plan. 65% of students were eating junk food for more than 3 days a week in their weekly diet. Moreover, 19.2%, 39.2%, 32.5%, and 25.84% of students were having their total cholesterol, triglycerides, HDL, and LDL levels above the optimum ranges respectively which were frequently found in students of final year (p < 0.05). There was high total cholesterol and LDL in males as compared to females (p value < 0.05). Total cholesterol and LDL were associated with skipped meal, use of junk food and carbonated drinks for more than 3 days a week (p < 0.05).ConclusionThere was a notable number of students with poor dietary habits, inactive lifestyle and lipid levels above the optimum ranges defined by American Heart Association (AHA) that have an association with dietary habits. This is alarming and can impact the health of future healthcare workers. There is a need to investigate the factors and remedies to help medical students to follow a healthy diet and a healthy lifestyle.

Abstract PO5-26-03: Evaluation of cardiotoxicity in Mexican patients with Breast Cancer under neoadjuvant treatment by two-dimension speckle echocardiography

Abstract Background Cardiotoxicity is a major concern in breast cancer patients treated with anthracyclines or anti-HER-2 therapy. The assessment of left ventricular ejection fraction (LVEF) by transthoracic echocardiogram (TTE) has been the most common method to evaluate cardiotoxicity. Different TTE parameters have been studied to assess cardiotoxicity, we aimed to evaluate left atrial strain (LAS) as a parameter of diastolic cardiotoxicity in Mexican patients under neoadjuvant treatment. Methods We prospectively recruited patients with breast cancer under neoadjuvant treatment with anthracyclines and/or anti-HER-2 from March 2022 to present. The evaluation includes TTE, and troponin measurements before chemotherapy, and respective follow-ups at 3 and 6 months from the baseline. We enrolled 187 patients, 172 and 131 had completed the three and six-month follow-ups, respectively. We limited the analysis to patients we could assess cardiotoxicity status, defined according to the ESC 2022 guidelines. Clinical and echocardiographic parameters were compared according to cardiotoxicity status using Chi-squared, two-tailed t-tests or Wilcoxon tests, as appropriate. Results The mean time of follow-up at second assessment was 213 days. The patients are divided into cardiotoxicity and no cardiotoxicity group. We reported 81 events of cardiotoxicity if we include troponin measurement or 36 events if we only evaluate TTE measurements. The incidence of cardiotoxicity in this study was not related with common risk factors as high BMI, presence of hypertension/diabetes or smoking status, but it was statistically associated with the presence of elevated LDL cholesterol (p 0.026). Fourteen percent (14%) were HR-/HER-2 (+), 44% HR+/HER-2 (-), 25% HR+/HER-2 (+), and 17% triple negative subtype. Eightyfive percent (85%) of patients received anthracyclines, 28% in combination with anti-HER-2 treatment, 12% received double anti-HER-2 blockade anthracycline free. The accumulated dose of anthracycline didn’t differ between groups. The use of anthracyclines and double anti/HER blockade was statically associated with development of CTRCD (p &amp;lt; 0.01 and p &amp;lt; 0.01), respectively, but not with a single anti-HER-2 treatment. In troponin-based cardiotoxicity definition, at the three-month follow-up, those who developed cancer therapy-related cardiac dysfunction (CTRCD) had only statically significant lower LVEF (Table 1) with respect to basal assessment. LASr baseline, three months and six months was similar between groups. In the cardiotoxicity group without troponin measurement, we observed statically significant decreased LVEF and LV GLS at 3 months and six months, and tendency to decreased LASr with respect to basal evaluation. Conclusions In our cohort the only modifiable risk factor with impact in the development of CTRCD was dyslipidemia, specifically high LDL. The traditional chemotherapy schemas as anthracyclines and doble anti HER-2 blockade correlate with the development of cardiotoxicity, but not the use of anti-HER-2 as single agent. The addition of troponin measurement to cardiotoxicity definition detected a greater number of events in this study, but doesn’t reflect changes in ETT parameters as LV- GLS and LVEF at this time of follow up, which means structural changes induced by treatment take time and serological measurement of troponin can enhance sensitivity and allows early detection. Further follow up and ETT assessment are needed. Table 1. Cardiotoxicity events including or not troponin levels and TTE parameters. Citation Format: Haydee Williams-Sanchez, Jose Rodrigo Espinosa-Fernandez, Sandy Ruiz-Cruz, Areli Velazquez-Martinez, Nilda Espinola-Zavaleta, Enrique C. Guerra, Alexis D Aparicio-Ortiz, Aldo Cabello-Ganem, Santiago Luna-Alcalá, Leonardo Proaño-Bernal, Neftali Eduardo Antonio-Villa. Evaluation of cardiotoxicity in Mexican patients with Breast Cancer under neoadjuvant treatment by two-dimension speckle echocardiography [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-03.

Serum lipid levels, genetic risk, and lung cancer incidence: A large prospective cohort study.

Previous studies usually focused on the separate association of metabolism or genetic factors with lung cancer risk and have largely ignored their combined effect. We aimed to examine the associations between serum lipid levels, genetic risk, and lung cancer risk. 426,524 participants of the UK Biobank were included. The Cox proportional hazards models and restricted cubic splines were performed to assess the association between serum lipid and lung cancer risk. Polygenic risk score (PRS) was constructed to assess its joint effect and interaction with serum lipid on lung cancer risk. Higher level of apolipoprotein A were significantly correlated with lower lung cancer risk. A inverse-J-shaped relationship between HDL and incident lung cancer was found. Individuals with low total cholesterol, HDL, LDL, apolipoprotein A, and apolipoprotein B, combined with high PRS, showed significantly elevated lung cancer risks. Compared to those with low PRS and low triglycerides, participants with high PRS and elevated triglyceride levels had a notably higher risk. The interaction effect of high PRS and low LDL (RERI:0.25, 95%CI: 0.04-0.46), as well as the interaction effect of high PRS and low apolipoprotein B (RERI:0.28, 95%CI: 0.07-0.48), were both greater than the sum of their individual effects on lung cancer risk. Serum lipids were associated with lung cancer risk. LDL or apolipoprotein B interacting with genetic risk may affect lung cancer risk. Our findings emphasize the need for individuals with heightened genetic risk should pay more attention to their lipid levels to reduce lung cancer risk.