Low-density Lipoprotein Cholesterol Measurement Research Articles

Coronary Artery Disease Risk of Familial Hypercholesterolemia Genetic Variants Independent of Clinically Observed Longitudinal Cholesterol Exposure.

Familial hypercholesterolemia (FH) genetic variants confer risk for coronary artery disease independent of LDL-C (low-density lipoprotein cholesterol) when considering a single measurement. In real clinical settings, longitudinal LDL-C data are often available through the electronic health record. It is unknown whether genetic testing for FH variants provides additional risk-stratifying information once longitudinal LDL-C is considered. We used the extensive electronic health record data available through the Million Veteran Program to conduct a nested case-control study. The primary outcome was coronary artery disease, derived from electronic health record codes for acute myocardial infarction and coronary revascularization. Incidence density sampling was used to match case/control exposure windows, defined by the date of the first LDL-C measurement to the date of the first coronary artery disease code of the index case. Adjustments for the first, maximum, or mean LDL-C were analyzed. FH variants in LDLR, APOB, and PCSK9 (Proprotein convertase subtilisin/kexin type 9) were assessed by custom genotype array. In a cohort of 23 091 predominantly prevalent cases at enrollment and 230 910 matched controls, FH variant carriers had an increased risk for coronary artery disease (odds ratio [OR], 1.53 [95% CI, 1.24-1.89]). Adjusting for mean LDL-C led to the greatest attenuation of the risk estimate, but significant risk remained (odds ratio, 1.33 [95% CI, 1.08-1.64]). The degree of attenuation was not affected by the number and the spread of LDL-C measures available. The risk associated with carrying an FH variant cannot be fully captured by the LDL-C data available in the electronic health record, even when considering multiple LDL-C measurements spanning more than a decade.

High Low-Density Lipoprotein Cholesterol Levels are Associated with Osteoporosis Among Adults 20-59 Years of Age.

BackgroundSerum lipids are highly inheritable and play a major role in bone health. However, the relationship between low-density lipoprotein cholesterol (LDL-C) and bone mineral density (BMD) remains uncertain. The goal of this study was to see if there was a link between LDL-C levels and BMD in persons aged 20 to 59.MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) 2011–2018, multivariate logistic regression models were utilized to investigate the association between LDL-C and lumbar BMD. Fitted smoothing curves and generalized additive models were also used.ResultsThe analysis included a total of 4909 adults. After controlling for various variables, we discovered that LDL-C was negatively linked with lumbar BMD. The favorable connection of LDL-C with lumbar BMD was maintained in subgroup analyses stratified by gender and race in both males and females, Whites and Mexican Americans, but not in Blacks and other races. The relationship between LDL-C and lumbar BMD in other races was an inverted U-shaped curve with the inflection point: 2.327 (mmol/L).ConclusionIn people aged 20 to 59, our research discovered a negative relationship among LDL-C and lumbar BMD. Among races other than Whites, Blacks, Mexican Americans, this relationship followed an inverted U-shaped curve (inflection point: 2.327mmol/L). LDL-C measurement might be used as a responsive biomarker for detecting osteoporosis early and guiding therapy.

No association of BMI and body adiposity with cardiometabolic biomarkers among a small sample of reindeer herders of sub-Arctic Finland

ABSTRACT The rising global obesity rate is alarming due to its real health and socioeconomic consequences. Finland, like other circumpolar regions, is also experiencing a rise in obesity . Here we assess BMI, body adiposity, and measures of cardiometabolic health among a small population of reindeer herders in sub-Arctic Finland. We collected anthropometric and biomarker measures at two different time points: October 2018 (N = 20) and January 2019 (N = 21) with a total of 25 unique individuals across the data collection periods (ages 20–64). Anthropometric measures included height, weight, age, and body composition. Biomarkers included measures of cholesterol, fasting glucose, HDL cholesterol, LDL cholesterol, and triglyceride levels. Over 70% of this sample was classified as “overweight” and “obese” as categorised by BMI and 64% classified as “overfat” based on body fat percentage. However, there was no significant relationship between BMI and body fat percentage with any of the measured biomarkers. Although the sample size is small, the results of this study suggest there might not be a strong correlation between BMI, body adiposity, and cardiometabolic health indices within this population – a pattern that has been documented elsewhere. However, further study is needed to confirm this lack of a correlation.

Optimism and Lipid Profiles in Midlife: A 15-Year Study of Black and White Adults

Optimism is associated with better cardiovascular health, yet little is known about the underlying mechanisms and whether protective relationships are consistently observed across diverse groups. This study examines optimism's association with lipid profiles over time and separately among Black and White men and women. Data were from 3,206 middle-aged adults in the Coronary Artery Risk Development in Young Adults study. Optimism was measured in 2000-2001 using the Revised Life Orientation Test. Triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol measurements were obtained at 5-year intervals through 2015-2016. Linear mixed models evaluated relationships between optimism and lipids, adjusting for covariates, including prebaseline lipids. Subgroup differences were examined using interaction terms and stratification. All analyses were conducted in 2020. Higher optimism was associated with both lower baseline total cholesterol (β= -2.33, 95% CI= -4.31, -0.36) and low-density lipoprotein cholesterol levels (β= -1.93, 95% CI= -3.65, -0.21) and a more rapid incremental increase in both markers over time (total cholesterol: β=0.09, 95% CI=0.00, 0.18; low-density lipoprotein cholesterol: β=0.09, 95% CI=0.01, 0.16). No associations were apparent with baseline triglycerides, high-density lipoprotein cholesterol, or changes in either lipid over time. Tests for interaction only found evidence of heterogeneous associations with baseline triglyceride levels, but stratified models hinted at stronger protective associations with baseline levels of total cholesterol and low-density lipoprotein cholesterol among White women. Optimism may help diverse individuals establish healthy total cholesterol and low-density lipoprotein cholesterol levels before midlife. Although associations were largely consistent across subgroups, stronger associations among White men and White women highlight a need to study optimism's health impact in diverse samples.

Assessing the Validity of Nine Different Formulae for LDL-C Estimation in a Tertiary Care Centre

Introduction: Conventionally, Friedewald’s formula has been used to calculate Low Density Lipoprotein- Cholesterol (LDL-C) due to its simplicity and convenience although it has limitations. Many researchers have proposed different formulae to increase the accuracy of calculated LDL-C, but none of those have concluded about a single best formula owing to differences in selected study populations. As LDL-C measurement is of utmost importance for assessing the cardiovascular risk according to National Cholesterol Education Programme’s (NCEP) Adult Treatment Panel III (ATP III), a search for a better formula to improve accuracy of cardiovascular disease (CVD) risk prediction is essential. Aim: To assess the validity of calculated LDL-C by nine formulae and compare them to values obtained by the direct method. Materials and Methods: A total of 324 participants were assessed retrospectively for serum lipid profile by standard methods from December 2020 to February 2021 at Employee State Insurance Corporation Medical College and Hospital, Sanathnagar, Hyderabad, Telangana, India. LDL-C was calculated using nine different formulae (Ahmadi, Anand, Chen, de Cordova, Friedewald, Hattori, Martin-Hopkins, Puavillai and Vujovic) and correlated with direct LDL-C. For further analysis, subjects were divided into five groups based on the triglyceride levels (TG) viz; group 1 (TG < 100 mg/dL), group 2 (TG:101-150 mg/dL), group 3 (TG:151-200 mg/dL), group 4 (TG: 201-400), group 5 (TG > 400 mg/dL). Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 23.0. Results: Total of 324 lipid profile reports were analysed and the calculated LDL-C by nine formulas were compared . At TG levels <100 mg/dL, Puavillai was the most accurate. Between TG levels 100-200 mg/dL, Martin-Hopkins showed better accuracy and correlation with direct LDL-C. At TG levels 200-400 and >400 mg/dL, Puavillai had better accuracy. But, none of the formulae showed strong correlation with Direct LDL-C at TG >400 mg/dL. ROC curves also showed that Puavillai performed better among all formulae, at all TG levels. conclusion: Among the nine equations, Puavillai and Martin- Hopkins showed highest accuracy and better performance than others in the present study population. Martin-Hopkins can be used at TG levels of 100-200 mg/dl while Puavillai can be used at lower and higher TG levels in this demographic population for estimating LDL-C.

Comparison between Values of Low Density Lipoprotein Cholesterol as Estimated by Direct Enzymatic Method with Calculated Methods Applying Friedewald’s Equation and Novel’s Equation: A Cross-sectional Study

Introduction: Lipid profile is routinely used as a screening test to identify the risk of Cardiovascular Diseases (CVD). Elevated Low Density Lipoprotein cholesterol (LDL-c) is an important modifiable risk factor of atherosclerotic CVD. The LDL-c lowering strategy is a known recommendation for the prevention and treatment of CVD. The gold standard method of LDL-c estimation is β-quantification by ultra centrifugation. Other methods include Direct LDL-c measurement (D-LDL-c) using enzymatic assay which is tedious, time consuming and expensive. Hence, calculated method using Friedewald’s equation (F-LDL-c) is routinely used in clinical laboratories in India. Aim: To compare LDL-c values as estimated by direct enzymatic method with LDL-c values obtained by Friedewald’s equation and Novel’s equation, and, also to assess the effects of LDL-c values obtained by both the methods towards the risk stratification of CVD. Materials and Methods: A cross-sectional study, was conducted in the Central Diagnostic Laboratory of Mandya Institute of Medical Sciences, Mandya, Karnataka, India, for a duration of three months from July to September 2020, where, 600 subjects, aged 20-75 years, visiting for routine lipid profile estimation were included. LDL-c was estimated by direct enzymatic method (D-LDL-c) and calculated methods using Friedewald’s {F-LDL-c=TC-HDL-c- (TG/5)} and Novel’s equation {N-LDL-c=TC-HDL-c-(TG/Adjustable factor)}. Values obtained by calculated methods were compared with D-LDL-c values. The LDL-c values obtained were compared at different ranges of Total Cholesterol (TC), Triglycerides (TG) and High-Density Lipoprotein cholesterol (HDL-c). The association between direct and calculated LDL-c values were analysed by Pearson’s correlation. Receiver Operator Characteristic Curve (ROC) analysis was done to predict the better diagnostic method among the calculated methods of LDL-c. Results: The mean±SD of D-LDL-c (115.68±36.94 mg/dL) was high compared to F-LDL-c (106.95±33.48 mg/dL) and N-LDL-c (110.78±32.58 mg/dL). The mean difference between D-LDL-c and N-LDL-c (4.9±4.36 mg/dL) was low compared to F-LDL-c (8.75±3.46 mg/dL). Significant positive correlation was observed between D-LDL-c vs F-LDL-c (r=0.96; p=<0.001) and D-LDL-c vs N-LDLc (r=0.97; p=<0.001). The ROC showed maximum AUC value for N-LDL-c than F-LDL-c at a cut-off value of 100 mg/dL. LDL-c as estimated by Novel’s and Friedewald’s equation led to approximately 5% and 10% less patients being subjects for lipid lowering therapy respectively as compared to D-LDL-c. Conclusion: In conclusion, the use of Novel’s equation for LDL-c estimation instead of Friedewald’s equation could be associated with the small net increase in lipid lowering agent eligible population for primary prevention of atherosclerotic CVD. Replacement of Friedewald’s equation by Novel’s equation would enable for the improved accuracy of LDL-c estimation especially at higher levels of TC, TG and lower levels of HDL-c.

Effect of a 1-Year Controlled Lifestyle Intervention on Body Weight and Other Risk Markers (the Healthy Lifestyle Community Programme, Cohort 2)

Introduction: The prevalence of obesity is high and increasing worldwide. Obesity is generally associated with an increased risk of chronic disease and mortality. The objective of the study was to test the effect of a lifestyle intervention on body weight and other chronic disease risk markers. Methods: A non-randomized controlled trial was conducted, including mostly middle-aged and elderly participants recruited from the general population in rural northwest Germany (intervention: n = 114; control: n = 87). The intervention consisted of a 1-year lifestyle programme, focussing on four key areas: a largely plant-based diet (strongest emphasis), physical activity, stress management, and community support. Parameters were assessed at baseline, 10 weeks, 6 months, and 1 year. The control group received no intervention. Results: Compared to the control, in the intervention group, significantly lower 1-year trajectories were observed for body weight, body mass index (BMI), waist circumference (WC), total cholesterol, calculated LDL cholesterol, non-HDL cholesterol, remnant cholesterol (REM-C), glucose, HbA1c, and resting heart rate (RHR). However, between-group differences at 1 year were small for glucose, HbA1c, and cholesterol (apart from REM-C). No significant between-group differences were found for 1-year trajectories of measured LDL cholesterol, HDL cholesterol, triglycerides, insulin, blood pressure, and pulse pressure. Conclusion: The intervention successfully reduced body weight, BMI, WC, REM-C, and RHR. However, at 1 year, effectiveness of the intervention regarding other risk markers was either very modest or could not be shown.

Low-density Lipoprotein Cholesterol Measurement Using the Direct Method Versus the Friedewald Equation, and the Clinical Background

Low-density Lipoprotein Cholesterol Measurement Using the Direct Method Versus the Friedewald Equation, and the Clinical Background

Abstract 10160: Population Eligible for PCSK9i in Spain: A Real-World Analysis

Background: Cardiovascular (CV) diseases are the leading cause of mortality globally. Reducing low-density lipoprotein cholesterol (LDL-C) is a proven strategy to decrease risk of acute CV events. The study aimed to estimate a PCSK9i-eligible population in Spain. Methods: We conducted a retrospective cohort study based on real-world data from the IQVIA Spanish Electronic Medical Records primary care database. Adult (≥18 y.o.) patients registered in the database between 2014 and 2020, diagnosed with myocardial infarction (MI), unstable angina (UA), ischemic stroke (IS), transient ischemic attack (TIA) or peripheral artery disease (PAD) and with at least 1 measurement of LDL-C or total cholesterol were included in the study and followed up for up to 12 months from the initial diagnosis. Results: The study included 9,516 patients; mean (SD) age was 67.7 (12.5) years, 63.9% were male and mean LDL-C was 117.3 (38.8) mg/dL. In the study population 28.5% of patients suffered an MI as most severe event during the study period, 10.0% had UA, 18.7% were diagnosed with IS, 13.6% with TIA, and 29.3% with PAD. At the time of last available LDL-C assessment (≥3 months after diagnosis), 64.4% of patients were on lipid lowering therapy (LLT). Of those, 45.4% were on high-intensity LLT (high-intensity statins with/without ezetimibe or PCSK9 inhibitors), 46.9% on moderate-intensity statins, and 7.7% on low-Intensity LLT (low-intensity statins, ezetimibe alone or non-statin LLT). Overall, 12.9% of treated patients achieved LDL-C levels <55 mg/dL; this proportion was the highest among those on high-intensity statins and any statin combined with ezetimibe (63.2%), followed by patients on moderate intensity statins (32.6%) and those on low-intensity LLTs (3.1%). A total of 17.1% of patients receiving optimized LLT had an LDL-C>100 mg/dL (LDL-C reimbursement threshold for PCSK9i in Spain). Conclusions: More than 85% of patients at very-high risk of cardiovascular events in our cohort do not achieve LDL-C <55 mg/dL recommended by 2019 ESC/EAS guidelines for management of dyslipidemia. More than 17% of the patients have LDL-C >100 mg/dL despite being treated with maximally tolerated LLT and, therefore, would be eligible for using PCSK9i within Spanish reimbursement criteria.

Decreased plasma lipid levels in a statin-free Danish primary health care cohort between 2001 and 2018

BackgroundLipid levels in blood have decreased considerably during the past decades in the general population partly due to use of statins. This study aims to investigate the trends in lipid levels between 2001 and 2018 in a statin-free population from primary health care, overall and by sex and age.MethodsIn a cohort of 634,119 patients from general practice with no diagnoses or medical treatments that affected lipid levels of total cholesterol (TC; n = 1,574,339) between 2001 and 2018 were identified. Similarly, measurements of low-density lipoprotein cholesterol (LDL-C; n = 1,302,440), high-density lipoprotein cholesterol (HDL-C; n = 1,417,857) and triglycerides (TG; n = 1,329,477) were identified.ResultsMean TC decreased from 5.64 mmol/L (95% CI: 5.63–5.65) in 2001 to 5.17 mmol/L (95% CI: 5.16–5.17) in 2018 while LDL-C decreased from 3.67 mmol/L (95% CI: 3.66–3.68) to 3.04 mmol/L (95% CI: 3.03–3.04). Women aged 70–74 years experienced the largest decreases in TC levels corresponding to a decrease of 0.7 mmol/L. The decrease in LDL-C levels was most pronounced in men ≥85 years with a decrease of 0.9 mmol/L. For both genders, TC and LDL-C levels increased with advancing age until around age 50. After menopause the women had higher TC and LDL-C levels than the men. The median (geometric mean) TG level decreased by 0.4 mmol/L from 2001 to 2008, after which it increased slightly by 0.1 mmol/L until 2018. During life the TG levels of the men were markedly higher than the women’s until around age 65–70. HDL-C levels showed no trend during the study period.ConclusionsThe levels of TC and LDL-C decreased considerably in a statin-free population from primary health care from 2001 to 2018. These decreases were most pronounced in the elderly population and this trend is not decelerating. For TG, levels have started to increase, after an initial decrease.

Comparison of Methods to Estimate Low-Density Lipoprotein Cholesterol in Patients With High Triglyceride Levels

Low-density lipoprotein cholesterol (LDL-C) is typically estimated with the Friedewald or Martin/Hopkins equation; however, if triglyceride levels are 400 mg/dL or greater, laboratories reflexively perform direct LDL-C (dLDL-C) measurement. The use of direct chemical LDL-C assays and estimation of LDL-C via the National Institutes of Health Sampson equation are not well validated, and data on the accuracy of LDL-C estimation at higher triglyceride levels are limited. To compare an extended Martin/Hopkins equation for triglyceride values of 400 to 799 mg/dL with the Friedewald and Sampson equations. This cross-sectional study evaluated consecutive patients at clinical sites across the US with patient lipid distributions representative of the US population in the Very Large Database of Lipids from January 1, 2006, to December 31, 2015, with triglyceride levels of 400 to 799 mg/dL. Data analysis was performed from November 9, 2020, to March 23, 2021. Accuracy in LDL-C classification according to guideline-based categories and absolute errors between estimated LDL-C and dLDL-C levels. Patients were randomly assigned 2:1 to derivation and validation data sets. Levels of dLDL-C were measured by vertical spin-density gradient ultracentrifugation. The LDL-C levels were estimated using the Friedewald method, with a fixed ratio of triglycerides to very low-density lipoprotein cholesterol (VLDL-C ratio of 5:1), extended Martin/Hopkins equation with a flexible ratio, and Sampson equation with VLDL-C estimation by multiple least-squares regression. A total of 111 939 patients (mean [SD] age, 52 [13] years; 65.0% male) with triglyceride levels of 400 to 799 mg/dL were included, representing 2.2% of 5 081 680 patients in the database. Across all individual guideline LDL-C classes (<40, 40-69, 70-99, 100-129, 130-159, 160-189, and ≥190), estimation of LDL-C by the extended Martin/Hopkins equation was most accurate (62.1%) compared with the Friedewald (19.3%) and Sampson (40.4%) equations. In classifying LDL-C levels less than 70 mg/dL across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (67.3%) compared with Friedewald (5.1%) and Sampson (26.4%) equations. In addition, for classifying LDL-C levels less than 40 mg/dL across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (57.2%) compared with the Friedewald (4.3%) and Sampson (14.4%) equations. However, considerable underclassification of LDL-C occurred. The magnitude of error between the Martin/Hopkins equation estimation and dLDL-C was also smaller: at LDL-C levels less than 40 mg/dL, 2.7% of patients had 30 mg/dL or greater differences between dLDL-C and estimated LDL-C using the Martin/Hopkins equation compared with the Friedewald (92.5%) and Sampson (38.7%) equations. In this cross-sectional study, the extended Martin/Hopkins equation offered greater LDL-C accuracy compared with the Friedewald and Sampson equations in patients with triglyceride levels of 400 to 799 mg/dL. However, regardless of method used, caution is advised with LDL-C estimation in this triglyceride range.

Management of High Cardiovascular Risk in Diabetic Patients: Focus on Low Density Lipoprotein Cholesterol and Appropriate Drug Use in General Practice.

This study aimed to evaluate the management of high cardiovascular risk (CVr) in the patients with diabetes by exploring the prescribing behavior in a setting of general practitioners (GPs). A retrospective cohort study was carried out using the data recorded between 2018 and 2020 in the clinical database of 10 GPs. Diabetes was defined using the International Classification of Diseases (ICD-9-CM) coding (250*) or using the laboratory parameters (hyperglycemia condition: ≥126 mg/dL). A cohort was described stratifying by demographic, clinical and therapeutic characteristics, and laboratory tests. Both the CVr and statin prescriptions were evaluated; adherence to statin therapy (medication possession ratio, MPR ≥ 80) was calculated in accordance with the low-density lipoprotein cholesterol (LDL-C) target. The multivariate logistic regression models with adjusted odds ratios (ORs) and the corresponding 95% Confidence Intervals (CIs) were calculated to identify the predictors of lipid modifying agents use and achieved target therapy; moreover, glucose-lowering drugs use was evaluated. Out of 13,206 people screened, 1,851 (14.0%) patients were affected by diabetes mellitus (DM), and 1,373 were identified at high/very high CVr. Of them, 1,158 (84.3%) had at least one measurement of LDL-C, and 808 (58.8%) received a prescription with at least one lipid-lowering drug (LLD). The patients at high/very high CVr treated or not treated with LLD, reached the LDL-C target in 24.0 and 10.3%, respectively (p < 0.001). Furthermore, 34.6% of patients treated with high intensity LLDs and adherent to therapy showed the LDL-C values below the therapeutic target. Out of 1,373 patients at high/very high CVr, 958 (69.8%) had at least one prescription of glucose-lowering drugs. Of them, 52.0% (n = 498) were prescribed not in agreement with the current guidelines. More specifically, 392 patients (40.9%) were treated with metformin only, while the remaining 106 (11.1%) were treated with metformin together with hypoglycemic agents other than glucagon-like peptide-1 receptor agonists (GLP1-RA) or sodium-glucose-transporter 2 (SGLT2) inhibitors. Our results suggest the urgent need to improve the management of patients with diabetes at high and very high CVr in the real life, to reduce the burden of diabetes on the health system.

A real-world assessment of treatment patterns in patients with atherosclerotic cardiovascular disease with hypercholesterolemia: a retrospective database analysis in Germany

Abstract Background The European Society of Cardiology (ESC) guidelines suggest that greater absolute reduction in low-density lipoprotein cholesterol (LDL-C) leads to greater cardiovascular risk reduction. Several lipid-lowering treatments (LLTs) are available in Germany; however, the research on treatment patterns and LDL-C outcomes among patients (pts) receiving LLTs in real-world setting is limited. Purpose To characterize the pts characteristics, treatment patterns and LDL-C outcomes of pts with atherosclerotic cardiovascular disease (ASCVD) with hypercholesterolemia (ASCVD-H) in Germany. Methods This is a descriptive, non-interventional, retrospective cohort study of ASCVD-H pts identified from general physician (GP) practices available in the electronic medical record (EMR) database Disease Analyzer (January 1992-June 2020) in Germany. ASCVD-H pts were included if they had a recorded diagnosis, were prescribed LLTs or had LDL-C levels of ≥55 mg/dL anytime within 6 months before and 3 months after the index date (ID), as per the data recorded by the participating physician. The first encounter of ASCVD after hypercholesterolemia during the identification period (1/07/2015–30/06/2019) was considered as the ID. Persistence was measured as the duration (in days) with allowed gap of 60 days and adherence as proportion of days covered (PDC) within 12 and 24 months after ID. Results We included 147,905 pts with ASCVD-H (57.2% male; mean age: 70.6 yrs; ≥75 yrs-old: 43.3%; mean BMI: 29.0 kg/m2). Coronary artery disease was the most common index diagnosis (73.2%), followed by cerebrovascular disease (31.7%) and peripheral vascular disease (21.5%). Hypertension (83.5%) and diabetes (27.6%) were the most common comorbidities among these pts. At ID, statin monotherapy (58.6%) was the most commonly prescribed LLT, with simvastatin being the most common drug (36.4%). The use of PCSK9 inhibitors, ezetimibe and fibrates was very limited (&amp;lt;1%; Table 1). Of note, LDL-C measurements (6 months prior and 3 months post index) were available for 50.7% of pts. In pts with uncontrolled LDL-C (≥55 mg/dL), 47.9% were receiving statin monotherapy (28.6% were on simvastatin), whereas there was no LLT prescribed in 48.0% of pts. The mean (SD) persistence and adherence to statins monotherapy within 24 months follow-up was 522 (260) days and 0.721 (0.345), respectively, with 60% of pts being adherent (PDC ≥0.80) to statins monotherapy. Conclusions Pts with ASCVD-H in Germany treated by GPs are elderly pts with multiple cardiovascular comorbidities. LDL-C was measured in nearly half of the pts, and almost all had LDL-C ≥55 mg/dL at ID. Findings indicate low prescription of LLTs in GP setting, particularly non-statin LLTs. The mean adherence (PDC) to statin monotherapy was 72% within the 24-month after ID. Data suggest the need for newer therapies with potential to control LDL-C levels. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis Pharma AG, Basel, Switzerland.

Treatment patterns in patients with Familial hypercholesterolemia: evidence from real-world studies in Germany and the UK

Abstract Background Familial hypercholesterolemia (FH) includes a spectrum of disease as per the number and effect of mutations in specific proteins involved in low-density lipoprotein cholesterol (LDL-C) metabolism, together with other genetic factors. Elevated LDL-C levels have been strongly associated with risk of cardiovascular and coronary heart disease, with up to 10-fold risk in patients (pts) with FH than without FH. The aim of lipid-lowering treatments (LLTs) is to reduce the LDL-C levels, although there is limited research describing treatment patterns and LDL-C outcomes in FH pts in routine care. Purpose To characterize the treatment patterns and LDL-C outcomes of FH pts in the real-world setting in Germany (GER) and the UK. Methods We conducted two descriptive, non-interventional and retrospective cohort studies. Pts in GER were identified from General Physician (GP) and Cardiology practices available in electronic medical records database Disease Analyzer (January 1992-June 2020). Pts in the UK were identified from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics admitted pts care and Office of National Statistics datasets. Pts were included if they had diagnosis of FH (index date [ID]) and data available within 6-month before and 3-month after the ID. The first diagnosis of FH in the identification period (GER, 1/07/2015–30/06/2019; UK, 01/01/2010–31/05/2018) was considered the ID. Persistence and adherence to the recorded LLT at ID was analyzed for pts with at least 12 months and 24 months of follow-up. Persistence was measured as the duration (in days) with allowed gap of 60 days and adherence as proportion of days covered (PDC). Results Analysis included 2,105 FH pts from GER and 9,846 from the UK. Data are presented as GER/UK. The mean (SD) age of pts was 60 (15)/52 (14) years, and 60%/61% were females. Hypertension (53%/27%) and depression (31%/38%) were the common comorbidities. At ID, statin monotherapy (29%/68%) was the most commonly prescribed LLT. The use of ezetimibe, fibrates and PCSK9 inhibitors was very low in both countries (Table 1). Of note, LDL-C measurements at ID (−6m/+3m) were available for 31%/73% of pts. In pts with uncontrolled LDL-C (≥55 mg/dL), 34%/64% were receiving statin monotherapy, whereas there was no use of LLT in 62%/29% of pts. During the 24 months follow-up, the mean (SD) persistence and PDC to statins monotherapy was 471 (264)/489 (289) days and 0.65 (0.36)/0.69 (0.46), respectively, with 50%/70% of pts being adherent (PDC ≥0.80). Conclusions In our study, in GER, the rate of LDL-C measurements was low. In both GER and UK, almost all measured patients had LDL-C ≥55mg/dL at ID. Findings indicate low prescriptions of LLTs in GP setting, particularly non-statin LLTs in both countries. The mean adherence (PDC) in GER and the UK was 65% and 69%, respectively within 24 months after ID. Improved LDL-C monitoring and new therapies with potential to lower LDL-C are warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis Pharma AG, Basel, Switzerland

Statin treatment and LDL-cholesterol treatment goal attainment among individuals with familial hypercholesterolaemia in primary care

ObjectivesGuidance recommends statin treatment in familial hypercholesterolaemia (FH) to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). We assessed statin prescribing rates and LDL-C treatment goal attainment...

Association Between Cumulative Low-Density Lipoprotein Cholesterol Exposure During Young Adulthood and Middle Age and Risk of Cardiovascular Events

Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease (CVD). Most observational studies on the association between LDL-C and CVD have focused on LDL-C level at a single time point (usually in middle or older age), and few studies have characterized long-term exposures to LDL-C and their role in CVD risk. To evaluate the associations of cumulative exposure to LDL-C, time-weighted average (TWA) LDL-C, and the LDL-C slope change during young adulthood and middle age with incident CVD later in life. This cohort study analyzed pooled data from 4 prospective cohort studies in the US (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis). Participants were included if they had 2 or more LDL-C measures that were at least 2 years apart between ages 18 and 60 years, with at least 1 of the LDL-C measures occurring during middle age at 40 to 60 years. Data from 1971 to 2017 were collected and analyzed from September 25, 2020, to January 10, 2021. Cumulative exposure to LDL-C, TWA LDL-C, and LDL-C slope from age 18 to 60 years. Incident coronary heart disease (CHD), ischemic stroke, and heart failure (HF). A total of 18 288 participants were included in this study. These participants had a mean (SD) age of 56.4 (3.7) years and consisted of 10 309 women (56.4%). During a median follow-up of 16 years, 1165 CHD, 599 ischemic stroke, and 1145 HF events occurred. In multivariable Cox proportional hazards regression models that adjusted for the most recent LDL-C level measured during middle age and for other CVD risk factors, the hazard ratios for CHD were as follows: 1.57 (95% CI, 1.10-2.23; P for trend = .01) for cumulative LDL-C level, 1.69 (95% CI, 1.23-2.31; P for trend <.001) for TWA LDL-C level, and 0.88 (95% CI, 0.69-1.12; P for trend = .28) for LDL-C slope. No association was found between any of the LDL-C variables and ischemic stroke or HF. This cohort study showed that cumulative LDL-C and TWA LDL-C during young adulthood and middle age were associated with the risk of incident CHD, independent of midlife LDL-C level. These findings suggest that past levels of LDL-C may inform strategies for primary prevention of CHD and that maintaining optimal LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic CVD.

Comparison of the effectiveness of Martin\u2019s equation, Friedewald\u2019s equation, and a Novel equation in low-density lipoprotein cholesterol estimation

Low-density-lipoprotein cholesterol (LDL-C) is the main target in atherosclerotic cardiovascular disease (ASCVD). We aimed to validate and compare a new LDL-C estimation equation with other well-known equations. 177,111 samples were analysed from two contemporary population-based cohorts comprising asymptomatic Korean adults who underwent medical examinations. Performances of the Friedewald (FLDL), Martin (MLDL), and Sampson (SLDL) equations in estimating direct LDL-C by homogenous assay were assessed by measures of concordance (R2, RMSE, and mean absolute difference). Analyses were performed according to various triglyceride (TG) and/or LDL-C strata. Secondary analyses were conducted within dyslipidaemia populations of each database. MLDL was superior or at least similar to other equations regardless of TG/LDL-C, in both the general and dyslipidaemia populations (RMSE = 11.45/9.20 mg/dL; R2 = 0.88/0.91; vs FLDL: RMSE = 13.66/10.42 mg/dL; R2 = 0.82/0.89; vs SLDL: RMSE = 12.36/9.39 mg/dL; R2 = 0.85/0.91, per Gangnam Severance Hospital Check-up/Korea Initiatives on Coronary Artery Calcification data). MLDL had a slight advantage over SLDL with the lowest MADs across the full spectrum of TG levels, whether divided into severe hyper/non-hyper to moderate hypertriglyceridaemia samples or stratified by 100-mg/dL TG intervals, even up to TG values of 500–600 mg/dL. MLDL may be a readily adoptable and cost-effective alternative to direct LDL-C measurement, irrespective of dyslipidaemia status. In populations with relatively high prevalence of mild-to-moderate hypertriglyceridaemia, Martin’s equation may be optimal for LDL-C and ASCVD risk estimation.

Use of Lipid-Lowering Therapies Over 2 Years in GOULD, a Registry of Patients With Atherosclerotic Cardiovascular Disease in the US

Guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) recommend intensive statin therapy and adding nonstatin therapy if low-density lipoprotein cholesterol (LDL-C) levels are 70 mg/dL or more. Compliance with guidelines is often low. To track LDL-C treatment patterns in the US over 2 years. GOULD is a prospective observational registry study involving multiple centers. Patients with ASCVD receiving any lipid-lowering therapy (LLT) were eligible. Between December 2016 and July 2018, patients were enrolled in 1 of 3 cohorts: (1) those currently receiving proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) and 2 groups not receiving PCSK9i drugs, with (2) LDL-C levels of 100 mg/dL or more or (3) LDL-C levels of 70 to 99 mg/dL. Patients had medical record reviews and telephone interviews every 6 months. Analysis was done on data collected as of October 5, 2020. The primary outcome was the change in LLT use in 2 years. Secondary outcomes included the number of LDL-C measurements, LDL-C levels, and responses to structured physician and patient questionnaires over 2 years. A total of 5006 patients were enrolled (mean [SD] age, 67.8 [9.9] years; 1985 women [39.7%]; 4312 White individuals [86.1%]). At 2 years, 885 (17.1%) had LLT intensification. In the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, LLT intensification occurred in 403 (22.4%) and 383 (14.4%), respectively; statins were intensified in 115 (6.4%) and 168 (6.3%), ezetimibe added in 123 (6.8%) and 118 (4.5%), and PCSK9i added in 114 (6.3%) and 58 (2.2%), respectively. In the PCSK9i cohort, 508 of 554 (91.7%) were still taking PCSK9i at 2 years. Lipid panels were measured at least once over 2 years in 3768 patients (88.5%; PCSK9i cohort, 492 [96.1%]; LDL-C levels ≥100 mg/dL or more, 1294 [85.9%]; 70-99 mg/dL, 1982 [88.6%]). Levels of LDL-C fell from medians (interquartile ranges) of 120 (108-141) mg/dL to 95 (73-118) mg/dL in the cohort with LDL-C levels of 100 mg/dL or more, 82 (75-89) to 77 (65-90) mg/dL in the cohort with LDL-C levels of 70 to 99 mg/dL, and 67 (42-104) mg/dL to 67 (42-96) mg/dL in the PCSK9i cohort. Levels of LDL-C less than 70 mg/dL at 2 years were achieved by 308 patients (21.0%) and 758 patients (33.9%) in the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, respectively, and 272 patients (52.4%) in the PCSK9i cohort. At 2 years, practice characteristics were associated with more LLT intensification (teaching vs nonteaching hospitals, 148 of 589 [25.1%] vs 600 of 3607 [16.6%]; lipid protocols or none, 359 of 1612 [22.3%] vs 389 of 2584 [15.1%]; cardiology, 452 of 2087 [21.7%] vs internal or family medicine, 204 of 1745 [11.7%] and other, 92 of 364 [25.3%]; all P < .001) and achievement of LDL-C less than 70 mg/dL (teaching vs nonteaching hospitals, 173 of 488 [35.5%] vs 823 of 2986 [27.6%]; lipid protocols vs none, 451 of 1411 [32.0%] vs 545 of 2063 [26.4%]; both P < .001; cardiology, 523 of 1686 [30.1%] vs internal or family medicine, 377 of 1472 [25.6%] and other, 96 of 316 [30.4%]; P = .003). Of patients with ASCVD, most with suboptimal LDL-C levels at baseline, only 17.1% had LLT intensification after 2 years, and two-thirds remained at an LDL-C level greater than 70 mg/dL. Further intensive efforts are needed to achieve optimal LDL-C management in patients with ASCVD.

Why Should We Measure Low-Density Lipoprotein Cholesterol Directly? Comparison of Low-Density Lipoprotein Cholesterol Assessment by Friedewald Estimation, and Direct Measurement

Intorduction: Plasma levels of low-density lipoprotein cholesterol (LDL-C) are an important biomarker for coronary artery disease. In clinical and research settings worldwide, levels LDL-C are often not measured and are estimated using the Friedewald equation (total cholesterol - HDL cholesterol - triglycerides)/5). Bias of either over or underestimation of LDL-C can be corrected by direct measurement of LDL-C. We assessed the precision of the Friedewald equation in a heterogonous patients population within a wide range of lipid levels. Methods: A sample of consecutive fasting lipid profiles was obtained from ambulatory and hospitalized patients at the Chaim Sheba Medical Center, Tel-Hashomer. LDL-C concentrations were directly measured (dir LDL-C) (Olympus, Ireland) and correspondingly calculated at by the Friedewald equation (calc LDL-C). Results: 32,245 samples were analyzed. In 93% of the samples, underestimation of plasma levels of LDL-C was observed using the Friedewald equation. In 11,054 patients (34.3%), the difference between dir LDL and calc LDL were over 10mg/dl. In 7,693 patients (23.8%), the difference between dir LDL and calc LDL were over 20mg/dl. The difference between dir LDL and calc LDL correlated with plasma TG levels, including TG levels within the normal range. The difference between cal LDL and dir LDL levels is inversely correlated to cholesterol plasma levels. Conclusions: Direct measurement of LDL-C is more precise than Friedewald’s formula and overcomes the inaccurateness, due to elevated TG levels or relatively low LDL-C levels, in the setting of a heterogeneous Israeli population. In the era of extremely low LDL-C treatment goals, our findings require consideration due to their clinical importance and direct measurement of plasma LDL-C should be implemented as underestimation of LDL levels may lead to inappropriate therapeutic decisions.

Performance of Methods to Estimate Low-Density Lipoprotein Cholesterol in Women With and Without HIV Infection.

Low-density lipoprotein cholesterol (LDL-C) is estimated from total cholesterol, high-density lipoprotein cholesterol and triglycerides using predefined equations which assume fixed or varying relationships between these parameters and may underestimate or overestimate LDL-C. Data on the performance of these equations in persons with HIV are limited. We sought to investigate the utility of the 3 most widely used methods (Friedewald, Hopkins, and the recently proposed NIH equation) to predict LDL-C in persons with HIV. We identified 7397 direct LDL-C (5219 HIV, 2127 uninfected controls, 51 seroconvertors) measurements in the Women's Interagency HIV Study, and used the 3 equations (Friedewald, Hopkins, and NIH) to calculate LDL-C. We compared the performance of the 3 equations using root mean square error and coefficient of determination (R2). Overall, the Friedewald equation had the best performance characteristics, outperforming Hopkins and NIH methods with lower root mean square error and higher R2 at lower triglyceride levels. However, this association did not hold true at higher triglyceride levels (quartiles 3 and 4), whereas the Hopkins equation had better performance characteristics in quartile 3, none of the 3 equations were optimal in quartile 4. After adjusting for fasting status and triglycerides levels, HIV+ had larger mean difference compared with directly measured LDL using all 3 methods. All 3 methods have lower accuracy in HIV+ vs HIV- women, even after adjusting for triglyceride levels and fasting status. Further research should focus on identifying methods to estimate LDL-C in HIV.