Mean Low-density Lipoprotein Cholesterol Research Articles

The Demographic and Lifestyle Characteristics of Patients with Familial Hypercholesterolemia Referred to a Dyslipidemia Clinic: A Cross-Sectional Single-Center Study

Background: Familial hypercholesterolemia (FH) is one of the most prevalent dyslipidemia disorders. This study investigated the demographic and lifestyle characteristics of patients with FH referred to a dyslipidemia clinic. Methods: This 5-year, single-center cross-sectional study focused on patients with low-density lipoprotein cholesterol (LDL-C) levels higher than 190 mg/dL referred to a dyslipidemia clinic in Tehran, Iran, between 2017 and 2022. The study examined their demographics, physical activity, and anxiety within the FH cohort. Results: A total of 1724 patients were referred to the dyslipidemia clinic. Of these patients, 44 were diagnosed with definite FH. The mean age and LDL-C level of the FH cohort were 38.84±16.85 years and 315.95±81.73 mg/dL, respectively. A significant correlation was found between LDL-C and body mass index (BMI) (correlation coefficient = -0.31, P=0.031) and total sleep duration (correlation coefficient = -0.40, P<0.000). No correlation was observed between age and physical activity or LDL-C levels. Additionally, no significant correlation was detected between the Dutch score and patients’ LDL-C, BMI, age, or physical activity. Regression analysis indicated that BMI and total sleep duration were independent predictors of LDL-C in the FH cohort. Conclusion: Investigating and identifying patients’ demographic and lifestyle characteristics is the first step in planning efficient and effective management strategies for chronic diseases, such as FH. Establishing a patient registry for chronic diseases enhances understanding of the target population and enables healthcare providers to design and implement appropriate preventive and control strategies.

Estimate and prognosis of patients who are candidates for treatment with eicosapentaenoic acid after an acute coronary syndrome

Abstract Background Treatment with eicosapentaenoic acid (EA) has been shown to reduce the incidence of cardiovascular adverse events (MACE) in patients at high cardiovascular risk with mildly to moderately elevated triglyceride values (>135 mg/dl) and non-elevated (<100 mg/dl) low-density lipoprotein cholesterol (LDLc). Methods We performed a multicenter and retrospective study using the ongoing registries of acute coronary syndrome (ACS) patients of 7 hospitals from Spain. Patients with LDLc <100 mg/dl and triglycerides >135 mg/dl were analyzed as candidates to EA. Results We included 14,483 patients discharged after an ACS, mean age 67.5 (13.3), 28.1% women and 30.4% with an ST-elevation ACS. Mean LDLc was 99.8 (38.5) mg/dl and median triglycerides 120.5 (interquartile range 90-197) mg/dl. A total of 3,028 (20.9%) were classified as candidates for EA, and they had the same mean age (p=0.87) but significantly higher prevalence of diabetes (35.1% vs. 21.9%), dyslipidemia (63.5% vs. 50.1%), previous coronary heart disease (CHD) (25.9% vs. 13.9%), or heart failure (HF) (3.6% vs. 2.5%). Candidates less frequently had an ST-elevation ACS (26.6% vs. 34.1%; p=0.02) and the incidence of Killip >1 was equivalent in candidates vs. non-candidates (16.6% vs. 17.7%; p=0.15). Median follow-up was 1223 (interquartile range 570-2040) days. All-cause mortality was 15.0% (n= 2,166), and 34.71% (n=5,019) of the patients experienced a first MACE. Candidates for EA had higher mortality (18.4% vs. 14.0%; HR: 1.22 95% CI 1.11-1.35) and MACE (39.0% vs. 33.6%; HR 1.14 95% CI 1.06-1.21) rates. Multivariate analysis (figure), adjusted for age, sex, diabetes (DM), previous coronary heart disease (CHD) or heart failure (HF), and medical treatments at discharge, identified an independently higher risk for all-cause mortality among candidates for EA (HR: 1.15 95% CI 1.04-1.26) [Figure 1] and for MACE (HR: 1.14 95% CI 1.05-1.20). The risk was consistent in all subgroups except for the case of mortality, but not for MACE, and previous ACS (figure 2) were a significant interaction (p=0.01) was observed Conclusions Approximately 20% of patients discharged after an ACS could be candidates for EA, and this subset of patients are at higher risk of death or a first MACE.

Applicability of VICTORION-1 PREVENT Criteria to the US Population

Abstract Background VICTORION-1 PREVENT (V-1P) is an ongoing randomized clinical trial comparing inclisiran sodium 300mg every six months with placebo for primary prevention in patients with high cardiovascular (CV) risk. Purpose We evaluated the generalizability of V-1P trial enrollment criteria to the US population to understand the demographic and CV health characteristics of the trial target population. Methods We included data from the National Health and Nutrition Examination Survey (N=25,531, 2015-March 2020), a nationally representative sample of the US population. Enrollment criteria similar to V-1P were applied. Nonpregnant adults 40-79 years with low-density lipoprotein cholesterol (LDL-C) of 70-189 mg/dL were included. 10-year risk for CV disease was determined using the American Heart Association race-free 10-year PREVENT risk equations. Individuals with 10-year risk >20% or 7.5%-19.9% with two risk enhancing factors at baseline were included. Risk enhancing factors included elevated high sensitivity C-reactive protein (≥2 mg/L), inflammatory arthritis, estimated glomerular filtration rate <60 ml/min/1.73 m2, metabolic syndrome, or early family history of CV disease. Patients with history of atherosclerotic CV disease or liver disease were excluded. Estimates of demographics and health characteristics were nationally representative using survey weights. Results Among US adults, 21,576,506 (standard error [SE]: ±1,258,255) meet eligibility criteria for V-1P (weighted estimate). This represents 8.8% of all US adults or 15.1% of US adults 30-79 years. The V-1P eligible population had a mean age of 65.3 years (SE: ±0.5 years), and 55.0% (SE: ±2.5%) were female. Compared with the US adult population (≥18 years), V-1P eligible population had a higher mean body mass index (32.6 ± 0.3 kg/m2 vs 29.5 ± 0.2 kg/m2) and higher rates of obesity (61.0% ± 2.1% vs 40.0% ± 1.1%) (Table). V-1P eligible population also had higher mean systolic blood pressure (133.9 ± 1.0 mmHg vs 121.7 ± 0.3 mmHg), similar mean diastolic blood pressure (72.6 ± 0.8 mmHg vs 71.8 ± 0.2 mmHg), and higher rates of hypertension (85.8% ± 2.0% vs 45.9% ± 1.1%). Mean hemoglobin A1c percent (6.3 ± 0.1 vs 5.7 ± 0.02), fasting blood sugar (127.7 ± 1.9 mg/dL vs 109.2 ± 0.6 mg/dL), and diabetes rates (39.7% ± 2.6% vs 13.1% ± 0.7%) were higher in the V-1P eligible population. Mean low-density lipoprotein cholesterol (115.8 ± 1.5 mg/dL vs 110.2 ± 0.8 mg/dL) and fasting triglycerides (137.6 ± 5.0 mg/dL vs 110.4 ± 1.7 mg/dL) were higher, while mean high-density lipoprotein cholesterol was lower (49.9 ± 0.8 mg/dL vs 54.8 ± 0.4 mg/dL). The distribution of key CV risk factors is shown in the Figure. Conclusion V-1P enrollment criteria apply to many patients. These patients have significant cardiometabolic risk factor burden, and effective preventive therapies could have substantial health impact.

Evaluating trends and insights in cardiovascular risk among the polish population

Abstract Introduction Cardiovascular diseases (CVD) are the leading cause of death in Poland and worldwide. Lifestyle changes and early diagnosis can reverse this unfavorable trend. In the face of escalating global health challenges, the identification of CVD risk factors becomes paramount, especially within national contexts where demographic shifts and lifestyle changes can significantly impact the health profile of the population. Aim of the study. Determining the prevalence of CVD risk factors in the Polish population and analyzing their changes over time. Material and Methods Data of 705,420 Poles aged 35-55 years who were enrolled in CVD disease prevention programme between 2012 and 2021 were analysed. The prevalence of the following CVD risk factors was determined: nicotinism, hypertension, elevated total cholesterol, elevated LDL, reduced HDL, elevated triglycerides, elevated glucose (indicating pre-diabetes), low physical activity, overweight, obesity, SCORE ≥5%. In addition, we assessed how the mean SCORE, BMI, systolic blood pressure, diastolic blood pressure, total cholesterol, LDL cholesterol, LDL cholesterol, triglycerides, glucose levels and waist circumference changed over time. Results Nicotinism affected 17.98%-24% of women (W) and 27.29%-36% of men (M). Hypertension was in 7.04%-8.58% of W and 17.45%-19.62% of M. Elevated total cholesterol were in 55.69%-63.64% of W and 65.91%-72.68% of M. Elevated LDL were in 44.77%-54.2% of W and 58.26%-65.48% of M. Reduced HDL were in 9.84%-11.52% of W and 14.48%-16.57% of M. Elevated triglyceride were in 13.44%-15.37% of W and in 33.81%-36.29% of M. Elevated glucose indicating a pre-diabetic status were in 10.70%-13.16% of W and in 18.91%-22.76% of M. Low physical activity was in 75.96%-82.2% of W and 73.32%-81.67% of M. Overweight conditions were in 30.37%-31.67% of W and 48.61%-49.45% of M. Obesity affected 14.04%-17.12% of W and 20.67%-24.69% of M. SCORE ≥ 5% was in 0.23%-0.38% of W and in 13.08%-18.72% of M. There was a decrease in the mean SCORE value (-0.08; 95%CI: -0.09 - -0.06) from 2012. An increase over time was noted in mean BMI (-0.01; 95%CI: -0.05 - 0.04). There was a slight decrease followed by a notable increase over time in mean systolic (-0.35; 95%CI: -0.47 - -0.24) and diastolic blood pressure (-0.25; 95%CI: -0.32 - -0.18). There was a decrease in mean total cholesterol (-3.29; 95%CI: -4.27 - -2.31) and mean LDL cholesterol (-3.11 95%CI: -4.22 - -2.01). A notable increase was observed in mean glucose values (0.01; 95%CI: 0-0.01). Over time, there was an increase in mean waist circumference value (-0.19; 95%CI: -0.54-0.16). Conclusions The escalation of CVD risk among the Polish population is illustrated, with a marked increase in obesity, sedentary lifestyles and indicators of metabolic syndrome. These trends highlight the urgent need for targeted public health initiatives and for the implementation of comprehensive strategies to mitigate these risks

Incidental detection and quantification of coronary artery calcification in ungated thoracic computed tomography for prognostic assessment. Preliminary results from the ICARUS registry

Abstract Background Coronary artery calcium (CAC) score improves cardiovascular risk stratification in asymptomatic individuals. However, whether CAC can be quantified in ungated thoracic computed tomography (uTCT) performed for other indications, and if this CAC score associates with cardiovascular outcomes, hasn’t been confirmed yet. Purpose We aim to analyse the extension of CAC and its prognostic value in terms of major adverse cardiovascular events (MACE) in patients who underwent uTCT for other indications. Methods We analysed a preliminary sample of 115 uTCT performed in 2015 in our hospital. We studied the presence and extension of CAC and quantified the global CAC score by Agatston method using validated software. Patients were categorized according to Coronary Artery Calcium Data and Reporting System (CAC-DRS) categories. Cardiovascular risk factors, lipidic control and pharmacological therapy of the cohort were registered. We analysed the time to first 3P-MACE, defined as cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, whichever occurred first. A p-value <0.05 was considered statistically significant. Results Mean age of the cohort was 60.8±16.1 years (53% male, 53% smokers). Mean LDL-cholesterol was 121.67±34.91 mg/dL, and 35.1% received lipid-lowering therapy. In more than half (n=59, 51.3%) of the population CAC was detected. Mean CAC score was 312.99±774.48 Agatston units, and patients were categorized in CAC-DRS category 1 (n=19, 16.5%), category 2 (n=15, 13%) and category 3 (n=25, 21.7%). Patients with CAC were older (71±10.1 vs. 50.1±14.2 years, p<0.001), had higher burden of cardiovascular risk factors and prevalence of chronic kidney disease (CKD; n=8, 13.6% vs. n=1, 1.8%, p=0.03) and higher levels of triglycerides (143.2±80.5 vs. 106.8±36.2 mg/dL, p=0.004), but not LDL-cholesterol. Eleven (9.6%) patients presented 3P-MACE during a mean follow-up of 6.55±2.82 years. CAC score independently predicted 3P-MACE (HR 1.06 [1.01-1.11] per 100 Agatston units, p=0.02) along with CKD (HR 6.94 [1.58-30.46], p=0.01) and basal glucose levels (HR 1.03 [1.02-1.04] per mg/dL, p<0.001). Conclusions CAC can be incidentally detected in more than half of our unselected cohort of patients undergoing uTCT for other indications. CAC score quantification by Agatston method is feasible in uTCT and associates with a higher risk of MACE during follow-up.Incidental CAC detection in uTCT

Efficacy of online japanese intensive cardiac rehabilitation for secondary prevention for coronary artery disease: a comprehensive program including exercise, nutrition, mindfulness, and group support

Abstract Background/Introduction While comprehensive programs for cardiac rehabilitation are recommended for patients with coronary artery disease (CAD), systematic programs including nutrition, stress-management, and behavior change have not been clearly established. Purpose To comprehensively change the lifestyle of patients with CAD as secondary prevention, we developed an online based educational program "intensive cardiac rehabilitation for Japanese patients with CAD (J-ICR)" modifying ICR, a regimen covered by health insurance in the United States, to the program that has affinity with Japanese. Methods Online J-ICR program is set up as sessions for maintenance-phase CAD patients using an online application. J-ICR has 12 sessions held weekly for 3 hours per session, total 36 hours, aimed to integrate 4 components: 1) exercise guidance based on exercise prescription which contain aerobic exercise, resistance training, and multi-component exercise through online platforms, 2) dietary education focusing on "the Japan Diet", 3) stress management utilizing mindfulness, and 4) group support to enhance patient and medical-staff interaction. Twenty-two participants were randomly separated to Early Phase group and Late phase group. For verification of the efficacy of this program, we survey the adherence to the program and compared the changes in risk factor of CAD at 3 months defining Early phase group as intervention group and Late phase group as control. (Fig.1). Results After excluding 3 participants who withdrawn to participate, the remaining 19 participants were conducted the evaluation and 10 participants were in intervention group and 9 participants in control group, respectively. As for patient characteristics, the mean age was 66 years old, and all participants were male. History of CVD was comprising 8 cases of myocardial infarction and 15 cases of angina pectoris. As for the risk factors of CVD, there were not significant differences in mean low density lipoprotein (LDL) cholesterol (Intervention group 71.5mg/dl vs Control group 83.4mg/dl; p=0.12) or systolic blood pressure (SBP) (126mmHg vs 130mmHg; p=0.40) at base line between two groups. The average participating rate in program was 93.8% and there was no dropped out participant during the program in investigation group. After 3months, LDL cholesterol was not significantly decreased in both groups (mean reduction of Intervention group -0.3mg/dl, p=0.93 and control group -3.8mg/dl, p=0.43, respectively). However, there was significant reduction of SBP in intervention group (mean reduction 5.6mmHg, p=0.02) but in control group (mean reduction 2.4mmHg, p=0.42). (Fig.2). Conclusions This randomized controlled study showed the good adherence of J-ICR program and it suggested that J-ICR program has the effect on lowering systolic blood pressure at 3 months. Longer follow up data and the results of more participants are warranted to clarify the efficacy in real world prevention of CVD.

Statin use before acute coronary syndrome and coronary risk factors, clinical presentation, interventions, and outcomes: ACC-NCDR-CathPCI Registry in India

Abstract Background Statins are used for coronary artery disease (CAD) primary and secondary prevention. Limited studies on the association of statin use before acute coronary syndrome (ACS) with clinical presentation and outcomes are available. Purpose We compared statin-user and statin-naïve ACS patients for clinical and angiographic findings and in-hospital and 3-year outcomes following percutaneous coronary intervention (PCI). Methods Successive patients with ACS who underwent PCI from Sep’17 to Dec’23 were enrolled in the ACC-NCDR-CathPCI registry in India. Details of risk factors, clinical presentation, coronary angiography, interventions and in-hospital were recorded. Follow-up data in a sub-cohort recruited from Apr’19 to Mar’22 were obtained for incident major cardiovascular events (MCE) (cardiovascular deaths, recurrent ACS, PCI and bypass surgery). Results 8296 ACS patients were enrolled; prior statin use was in 3149 (38%) and statin naïve were 5147 (62%). Statin-user vs statin-naïve patients were older (61.6+10 vs 59.7+11y), with more hypertension (60.1 vs 48.6%), diabetes (35.8 vs 31.8%), pre-existing CAD (PCI 20.9 vs 9.1%; CABG 5.0 vs 2.3%) and lower mean total, LDL, and NHDL cholesterol (p<0.001). Statin users had less ST-elevation myocardial infarction (STEMI) (28.4% vs 45.2%), more non-STEMI (65.2 vs 50.8%), better LVEF (46.3+10 vs 44.5+10%), >2 coronary stents (35.5 vs 29.5%), lower mechanical circulatory support (2.2 vs 3.9%) and lower median hospitalization (66.1 vs 68.5h) (p<0.001). In statin-users incidence of in-hospital CAD deaths was 29 (0.92%) vs 78 (1.52%) (odds ratio, OR 0.61, 95% confidence intervals 0.39-0.93) and all-cause deaths 33 (1.05) vs 91(1.77%) (OR 0.59, 95%CI 0.39-0.88) (p<0.01). ORs attenuated following multivariate adjustments for risk factors, clinical presentation and interventions. In the follow up cohort (n=3813, high-intensity statins 99.6%), among baseline statin-users incident MCE was 98 (6.9%) vs 214 (8.9%) (hazard ratio, HR 0.76, 95%CI 0.59-0.97) and CVD deaths were in 46 (3.2%) vs 113 (4.7%) (HR 0.68, 95%CI 0.48-0.96) with attenuation following adjustment for baseline clinical variables and interventions. Conclusions Acute coronary syndrome patients taking pre-admission statins have significantly lower in-hospital and long-term cardiovascular and all-cause mortality following PCI.

Lp(a) testing and LDL-C levels among australian ASCVD patients in 2022: a cross-sectional study from the advara heartcare network (PREVAIL)

Abstract Background The proportion of Australians with atherosclerotic cardiovascular disease (ASCVD) who meet secondary prevention low-density lipoprotein cholesterol (LDL-C) targets is uncertain, particularly among those undergoing lipoprotein(a) (Lp(a)) testing. This study describes the characteristics and achievement of LDL-C targets in ASCVD patients, both with and without Lp(a) tests. Methods A cross-sectional study was performed utilising secondary data from the Advara HeartCare cardiology network electronic medical records (EMR). Natural language processing (NLP) was used to extract data from clinical letters between 2011 and 2022 for patients attended during 2022. The 2022 baseline report captures clinical characteristics (i.e,. comorbidities, medications, lab values) in those with and without Lp(a) tests. Results In 2022, a total of 55,427 ASCVD patients were identified, predominantly male (65.1%) with a mean age of 71.2 (12.3). 61% had dyslipidaemia, 58.6% had hypertension, and 21.4% had diabetes. 72.7% were on statins, 19.4% on ezetimibe and 5.6% on PCSK9i. LDL-C information was available for 60.2% (33,381) of all ASCVD patients, with a mean LDL-C of 2.0 mmol/dL. 47.6% and 21.4% had LDL-C levels <1.8 mmol/dL and <1.4 mmol/dL respectively. Lp(a) test results were available for 2.6% (n=1,460) of ASCVD patients, with 87.7% having LDL-C information available, and a mean LDL-C of 1.9 mmol/dL. Among this group, 54.5% and 25.1% had LDL-C levels <1.8 mmol/dL and <1.4 mmol/dL respectively. Conclusions The study highlights suboptimal achievement of LDL-C targets among both ASCVD patients and those tested for Lp(a), underscoring the need to improve secondary prevention strategies and Lp(a) measurement in the ASCVD population.

Efficacy of combination lipid lowering therapy in achieving low density lipoprotein cholesterol targets after one month of event in patients with acute coronary syndrome

Abstract Introduction Rapid reduction in low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of recurrent events in patients with acute coronary syndrome (ACS) with benefits proportional to LDL-C reduction. Early use of combination lipid-lowering therapy (LLT) is therefore recommended. Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) combined with high-intensity statins (HIS) improve LDL-C goal attainment but are unaffordable for many patients in India and worldwide. Purpose We share our experience with the use of dual RE (rosuvastatin plus ezetimibe) and triple REB (rosuvastatin plus ezetimibe and bempedoic acid) combination LLT in patients admitted with ACS. Methods All ACS patients admitted to our institute over one year (January 2023 to December 2023) were considered in this retrospective analysis. Those with unavailable lipid profile reports, either at the time of ACS or at 1-month follow-up, were excluded. Clinical and laboratory details were obtained from hospital records. The primary objective was to assess the percentage change in LDL-C levels from index event to 4 weeks follow-up. Results A total of 299 patients were included, out of which 60 were on HIS alone, 71 were on RE, and 168 were on REB (Figure). The majority (99%) of patients in the REB group were statin naïve, compared to the other two groups. The baseline mean LDL-C levels at the time of the index event were 95.3+30.5, 103.2+39.6, and 115.6+32.9 mg/dl, respectively (p<0.001) (Table). The mean LDL-C levels at four weeks post-ACS reduced to 52.9+21.2, 45.9+20.5, and 43.7+15.4 mg/dl, respectively (p<0.01). The percentage reduction in LDL-C level was 44.4%, 55.5%, and 62.2%, respectively (p<0.001). REB enabled 70.8% and 95.2% of patients to achieve the Lipid Association of India, and American College of Cardiology recommended LDL-C targets of <50 mg/dl and <70 mg/dl within 4 weeks. These target levels were achieved in 67.6% and 88.7% of patients on the dual RE therapy and 50% and 81.6% of patients, respectively, on HIS alone. Conclusion Our study demonstrates the capacity to rapidly achieve LDL-C goals after ACS with triple REB therapy, an affordable regimen compared to costly PCSK9i therapy.Figure.Lipid lowering strategies usedComparison of study groups

Evaluating the Efficacy of a Pre-Established Lipid-Lowering Algorithm in Managing Hypercholesterolemia in Patients at Very High Cardiovascular Risk.

Recent data from European studies (EUROASPIRE V, DA VINCI, SANTORINI) indicate that achieving the LDL cholesterol (LDL-C) target in patients at very high cardiovascular risk is uncommon. Additionally, using a combination therapy involving statins and ezetimibe remains infrequent. A single-center assessment of a pre-defined lipid lowering treatment algorithm's effectiveness at achieving the LDL-C target in patients at very high cardiovascular risk one month and one year after hospitalization. 81 patients were included, all in secondary prevention. The average age of the patient was 66.9 years, and the main cardiovascular risk factors included hypertension, diabetes mellitus, and smoking history. Following the predefined lipid-lowering algorithm specific to our study, which involves initiating high-intensity statin therapy or a combination of statin and ezetimibe depending on initial LDL-C levels and patient history; 30 (37%) patients initiated high-intensity statin therapy (Atorvastatin (40 mg, 80 mg) or Rosuvastatin (20 mg, 40 mg)), while 51 (63%) started combination therapy with high-intensity statin and ezetimibe 10 mg. After one year, 57 (70.4%) remained adherent to their initial treatment, achieving a mean LDL-C of 49.5 ± 16.9 mg/dL, with 36 (63.2%) of them reaching the LDL-C target of <55 mg/dL. A total of 13 patients discontinued treatment, and 9 were lost to follow-up, withdrew from the study, or died. Initiating dual statin and ezetimibe therapy or high-intensity statin therapy early, based on the expected treatment efficacy, holds the potential to more rapidly and effectively achieve LDL-C targets in a larger proportion of very high-risk cardiovascular patients.

7055 Metabolic Disorders In Thalidomide Embryopathy

Abstract Disclosure: A. Tanabe: None. Thalidomide embryopathy (TE) is a congenital limb defect that occurs in neonates born to pregnant women who have taken thalidomide. Typical abnormalities of the TE are upper limb hypoplasia and and/or auditory dysfunction. In Japan, thalidomide was marketed as an agent for sleep-induce and digestive ulcers from 1958 to 1962. Up to now, approximately 290 cases have been certified and are supported by the government as drug-induced disease. Currently, many of the victims are in their late 50s, and in addition to congenital disabilities, various health issues such as lifestyle-related diseases can be developed. We investigated their metabolic condition using data of medical health checkup between 2017 and 2018. Fifty-one Japanese cases of TE (28 men and 23 women) were included in this study. The mean age was 56.4±1.6 years in men and 55.9±1.2 years in women. The prevalence of upper limb deformities was 64% in men and 74% in women; the remaining patients had only hearing impairment. The mean body mass index (BMI) was 22.7±2.1 in men and 22.5±4.0 in women. Eleven percent of men and 17% of women had a BMI between 25-30, while 9% of women and no men had a BMI of 30 or greater. Liver dysfunction was seen in 32% of men and 9% of women. The mean high-density lipoprotein cholesterol level was 60±17 mg/dL in men and 68±18 mg/dL in women. The mean low-density lipoprotein (LDL) cholesterol level was 120±28 mg/dL in men and 136±35 mg/dL in women, with 25% of men and 48% of women had LDL level of 140 mg/dL or greater. The mean triglyceride (TG) level was 144±85 mg/dL in men and 116±61 mg/dL in women, with 43% of men and 17% of women had a level of 150 mg/dL or greater. The mean HbA1c level was 6.0±1.0% in men and 5.9±0.4% in women. The prevalence of impaired glucose tolerance was 25% in men and 13% in women. Fatty liver (FL) evaluated by ultrasonography or CT scan was 61% in men and 39% in women. The patients with FL showed significantly high body fat percentage and TG level in men, high alanine aminotransferase, γ-glutamyl transpeptidase and TG levels in women, respectively, compared to the patients without FL. The prevalence of hypertriglyceridemia was significantly higher in men with FL compared with men without FL. There was no significant difference in with or without the upper limb abnormalities in both groups. Although without obvious overweight, more than 40 % of the patients had dyslipidemia and 50% of the patients had FL. The limb abnormalities can result in movement limitations however other factors may be involved in the development of metabolic disorders in TE. The results of this study provide valuable information for future health management in thalidomide embryopathy. (This study was conducted by a research grant from the National Center for Global Health and Medicine, Japan: 21A1015 and a Grant-in-Aid from the Ministry of Health, Labour, and Welfare, Japan: 20KC2005, 23KC2017). Presentation: 6/2/2024

Does Adopting Western Low-density Lipoprotein Cholesterol Targets Expose Indians to a Higher Risk of Cardiovascular Events? Expert Opinion From the Lipid Association of India.

Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India.

Addition of Ezetimibe to Intensive Lipid-Lowering Therapy Is Associated With a Lower Incidence of Heart Failure in Patients With Acute Coronary Syndrome.

This study investigated whether intensive lipid-lowering therapy with pitavastatin and ezetimibe lowers the incidence of heart failure (HF) events in patients with acute coronary syndrome (ACS). In the HIJ-PROPER study, 1,734 patients with ACS were randomly assigned to either pitavastatin plus ezetimibe therapy (n=864) or pitavastatin monotherapy (n=857). We examined the incidence of HF between these 2 groups over a 3.9-year period after ACS. The primary endpoint of the study was hospitalization for HF. The mean low-density lipoprotein cholesterol levels during the follow-up period were 65.1 mg/dL in the pitavastatin plus ezetimibe group and 84.6 mg/dL in the pitavastatin monotherapy group. The incidence of HF hospitalization was significantly lower in the pitavastatin plus ezetimibe group than in the pitavastatin monotherapy group (19 [2.2%] vs. 40 [4.7%] patients; hazard ratio 0.47, 95% confidence interval 0.27-0.81; P<0.005). This trend was consistent after multivariable analysis using multiple models. Intensive lipid-lowering therapy with pitavastatin and ezetimibe is associated with a lower incidence of hospitalization for HF in patients with ACS.

Efficacy of Food Supplement Based on Monacolins, γ-Oryzanol, and γ-Aminobutyric Acid in Mild Dyslipidemia: A Randomized, Double-Blind, Parallel-Armed, Placebo-Controlled Clinical Trial.

The risk of cardiovascular disease (CVD) is approximately doubled in subjects with hypercholesterolemia compared to those with normal blood cholesterol levels. Monacolin K (MK), the main active substance in rice fermented by the Monascus purpureus, acts on cholesterol metabolism. Rice also contains other bioactive compounds such as γ-oryzanol (OZ) and γ-aminobutyric acid (GABA). In a randomized, placebo-controlled, double-blind trial, the efficacy and tolerability of a food supplement (FS) based on an ingredient standardized to contain monacolins (4.5%), OZ, and GABA were evaluated in subjects with mild dyslipidemia. For the duration of the trial, enrolled subjects (n = 44, each group) received the FS or placebo and were instructed to use an isocaloric diet. Compared to the placebo group, after a 3 months of the FS, the mean low-density lipoprotein cholesterol and mean TC values were reduced by 19.3 and 8.3%, respectively, while the mean high-density lipoprotein cholesterol value increased by 29.3%. On average, the subjects shifted from very high to moderate CVD risk. Glucose metabolism and hepatic and renal parameters did not change after the treatment and no adverse events were reported. Guidelines to handle hypercholesterolemia with food supplements in specific clinical settings are needed to better manage mild dyslipidemia.

Rare Genetic Variants in LDLR, APOB, and PCSK9 are Associated with Aortic Stenosis.

Background: Despite a proposed causal role for low-density lipoprotein cholesterol (LDL-C) in aortic stenosis (AS), randomized controlled trials of lipid-lowering therapy failed to prevent severe AS. We aimed to assess the impact on AS and peak velocity across the aortic valve conferred by lifelong alterations in LDL-C levels mediated by protein-disrupting variants in three clinically significant genes for LDL metabolism (LDLR, APOB, PCSK9). Methods: We utilized sequencing data and electronic health records from UK Biobank (UKB) and All of Us and magnetic resonance imaging data from UKB. We identified predicted protein-disrupting variants with the LOFTEE and AlphaMissense algorithms and evaluated their associations with LDL-C and peak velocity across the aortic valve (UK Biobank), as well as diagnosed AS and aortic valve replacement (UK Biobank + All of Us). Results: We included 421,049 unrelated participants (5,621 with AS) in UKB and 195,519 unrelated participants (1,087 with AS) in All of Us. Carriers of protein-disrupting variants in LDLR had higher mean LDL-C (UKB: +42.6 mg/dl, P=4.4e-237) and greater risk of AS (meta-analysis: odds ratio [OR] =3.52 [95% CI 2.39-5.20], P=2.3e-10) and aortic valve replacement (meta-analysis: OR=3.78 [95% CI 2.26-6.32], P=4.0e-7). Carriers of protein-disrupting variants in APOB or PCSK9 had lower mean LDL-C (UKB: -32.3 mg/dl, P<5e-324) and lower risk of AS (meta-analysis: OR=0.49 [0.31-0.75], P=0.001) and aortic valve replacement (meta-analysis: OR=0.54 [0.30-0.97], P=0.04). Among 57,371 UKB imaging substudy participants, peak velocities across the aortic valve were greater in carriers of protein-disrupting variants in LDLR (+12.2cm/s, P=1.6e-5) and lower in carriers of protein-disrupting variants in PCSK9 (-6.9cm/s, P=0.022). Conclusions: Rare genetic variants that confer lifelong higher or lower LDL-C levels are associated with substantially increased and decreased risk of AS, respectively. Early and sustained lipid-lowering therapy may slow or prevent AS development.

Lipid and glucose profiles in pregnant women with HIV on tenofovir-based antiretroviral therapy.

Tenofovir alafenamide (TAF)-based antiretroviral therapy (ART) regimens have been associated with adverse changes in lipid and glucose profiles compared with tenofovir disoproxil fumarate (TDF)-based ART, but data in pregnancy is limited. We evaluated metabolic markers in pregnant women with HIV after starting TAF- vs TDF-based ART. We analyzed data within the IMPAACT 2010/VESTED trial, which demonstrated better pregnancy outcomes in pregnant women randomized to initiate TAF/Emtricitabine/Dolutegravir (TAF/FTC+DTG; n=217) or TDF/FTC+DTG (n=215). We measured non-fasting plasma concentrations of glucose, total-cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), lipoprotein (a), and triglycerides from samples collected eight weeks after enrollment. We employed linear regression models to estimate by-arm mean differences. 219 participants enrolled in the DTG arms in Zimbabwe and Uganda: 109 in the TAF/FTC+DTG and 110 in the TDF/FTC+DTG arms. At study entry, mean gestational age was 22.6 weeks, median HIV-1 RNA was 711 copies/mL, and mean age was 25.8 years. By eight weeks, mean total cholesterol was 12 mg/dL higher in women randomized to TAF/FTC+DTG versus TDF/FTC+DTG (95% CI 3.8, 21.1). Pregnant women in the TAF/FTC+DTG arm had higher mean LDL-C (7.1 mg/dL, 95% CI 0.2, 14.0), triglycerides (12.3 mg/dL, 95% CI 1.8, 22.7), lipoprotein (a) (7.3 mg/dL, 95% CI 1.1, 13.6), and lower mean HDL-C (2.8 mg/dL, 95% CI 0.1, 5.6) compared to the TDF/FTC+DTG arm. Pregnant women randomized to start TAF/FTC+DTG had higher lipids than those randomized to TDF/FTC+DTG within eight weeks of ART initiation. However, lipid levels were within normal reference ranges.

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.

Mean LDL cholesterol levels that reaches the ACS threshold and affecting factors

Mean LDL cholesterol levels that reaches the ACS threshold and affecting factors

Metformin versus Metformin Plus Statin Effect on Lipid Profile in Type 2 Diabetic Patients

Metformin is commonly used drug for type 2 diabetes and may also impact lipid profiles. Statins are often combined with metformin to manage dyslipidemia, but their comparative efficacy on lipid profiles is not well established. This study aimed to compares the effects of metformin alone versus metformin with statins on lipid profiles and to investigate the impact of different metformin doses on these profiles. A cross-sectional study was conducted at Aljabal Alakdar Diabetic Clinic in East Libya from July to December 2023, involving 200 adults with type 2 diabetes. Participants were divided into Group A (metformin only) and Group B (metformin plus statin). Inclusion criteria were adults aged 18-75 years, on metformin for at least 3 months, with recent lipid profile data, and who provided informed consent. Exclusion criteria were additional lipid-lowering drugs or any medications known to affect lipid profiles, type 1 diabetes, severe comorbidities, and pregnancy. Data were analyzed using SPSS version 27 with MANOVA, and significance was set at p &lt; 0.005. The mean age was 58.62 years, mean diabetes duration was 11.43 years, with 47.5% males and 52.5% females. Mean HbA1c was 7.98%, mean urea was 36.5 mg/dL, and mean creatinine was 0.95 mg/dL. Lipid profile parameters included mean LDL cholesterol at 89.09 mg/dL, HDL cholesterol at 47.71 mg/dL, total cholesterol at 175.6 mg/dL, and triglycerides at 169.4 mg/dL. The key lipid parameters showed a significant difference (p &lt; 0.000) between groups, with the metformin-only group exhibiting lower LDL, HDL, triglycerides, and total cholesterol compared to the metformin plus statin group. Our study found that metformin alone achieved better lipid control than metformin combined with statins, with a 1g dose showing notable antihyperlipidemic effects.

Cut-off values of coronary risk factors in women with hypothyroidism.

Women with hypothyroidism are at higher risk of cardiovascular diseases and the consequent mortality. It is not known whether cut-off values of coronary risk factors in women with hypothyroidism are the same as healthy women. This may help to initiate interventions as early to prevent cardiovascular mortality. Therefore, this study was conducted to determine the cut-off values of coronary risk factors in women with hypothyroidism. One hundred women patients with hypothyroidism were compared with 100 healthy controls. Significantly higher mean body mass index (BMI), waist circumference (WC), triglycerides and low-density lipoprotein cholesterol (LDL-C) were observed in women with hypothyroidism than without it. All variables showed an area under curve (AUC) value of >0.6 in receiver operator characteristic curve (ROC) analysis, and similar to healthy women.