Cholesterol-lowering Therapy Research Articles

Inclisiran-A Revolutionary Addition to a Cholesterol-Lowering Therapy.

Hypercholesterolemia plays a crucial role in the development of atherosclerosis, but it remains an undertreated and underdiagnosed disease. Taking into consideration the high prevalence of lipid disorders, long duration of the asymptomatic course of the disease, life-threatening complications resulting from inaccurate therapy, and stringent treatment goals concerning LDL cholesterol level in the prevention of cardiovascular events, novel lipid-lowering therapies have been introduced in the last few years. In this article, a drug belonging to the group of small interfering RNA (siRNA) called inclisiran is described. It is a novel molecule that increases the number of LDL receptors (LDLRs) on the surface of hepatic cells by preventing the formation of proprotein convertase subtilisin/kexin type 9 (PCSK9) responsible for the degradation of LDLRs. With great potential for lowering plasma LDL cholesterol level, high liver specificity, comfortable dosing regimen, and good tolerance without significant adverse effects, it could play an important part in future hypolipemic therapies.

Inflammation Beats Cholesterol: A Comment on the Unequivocal Driver of Cardiovascular Disease Risk.

Despite advancements in the current standard of care, cardiovascular diseases continue to hold the top spot as the leading cause of mortality worldwide. The development of atherosclerosis is the most common culprit behind ailments such as myocardial infarction, stroke, and peripheral vascular disease. Consequently, it imposes a significant burden on life expectancy, quality of life, morbidity, and societal costs. Both increased cholesterol levels and the activation of the inflammatory cascade are known as cardiovascular risk facts. Their relative weight is in the spotlight of curent biomedical research. Newly published data shed light on the role of inflammation in determining cardiovascular risk irrespective of cholesterol levels and cholesterol-lowering therapies.

Evaluating Statin Knowledge-Perceptions and Receptivity Following a Comprehensive Lifestyle Modification Program

Background Though clinical guidelines for cholesterol-lowering therapies advocate for both a trial of lifestyle modification and the initiation of statin medication when appropriate, the extent to which lifestyle modification may alter a patient’s knowledge-perceptions and receptivity towards statins remains unclear. Methods Following completion of a 6-month comprehensive lifestyle modification program, perceived changes in knowledge and receptivity towards statins were examined across prespecified subgroups of age, sex, and statin eligibility using a mixed-methods questionnaire. Quantitative and qualitative analyses incorporated binomial tests, McNemar’s test, and thematic analyses. Results Among 192 patients who completed the program and exit questionnaire between December 15, 2020 and July 2, 2021, 88.4% of patients indicated a perceived improvement in cholesterol and/or statin knowledge (P < . 0001). 48.2% of patients acknowledged that their receptivity towards taking statins increased (P = . 61). Changes in receptivity were attributed to several identified program themes including improvements in health knowledge and awareness, motivation and empowerment. Patients who noted improvements in their mental health also reported significantly increased receptivity towards statins (P < . 001). Conclusions Patients’ perceived knowledge and receptivity towards statins may improve following participation in a comprehensive therapeutic lifestyle modification program. Future research must evaluate the impact of these programs on statin uptake, compliance and outcomes.

Intensive cholesterol-lowering treatment reduces synovial inflammation during early collagenase-induced osteoarthritis, but not pathology at end-stage disease in female dyslipidemic E3L.CETP mice

The association between metabolic syndrome (MetS) and osteoarthritis (OA) development has become increasingly recognized. In this context, the exact role of cholesterol and cholesterol-lowering therapies in OA development has remained elusive. Recently, we did not observe beneficial effects of intensive cholesterol-lowering treatments on spontaneous OA development in E3L.CETP mice. We postulated that in the presence of local inflammation caused by a joint lesion, cholesterol-lowering therapies may ameliorate OA pathology. Female ApoE3∗Leiden.CETP mice were fed a cholesterol-supplemented Western type diet. After 3 weeks, half of the mice received intensive cholesterol-lowering treatment consisting of atorvastatin and the anti-PCSK9 antibody alirocumab. Three weeks after the start of the treatment, OA was induced via intra-articular injections of collagenase. Serum levels of cholesterol and triglycerides were monitored throughout the study. Knee joints were analyzed for synovial inflammation, cartilage degeneration, subchondral bone sclerosis and ectopic bone formation using histology. Inflammatory cytokines were determined in serum and synovial washouts. Cholesterol-lowering treatment strongly reduced serum cholesterol and triglyceride levels. Mice receiving cholesterol-lowering treatment showed a significant reduction in synovial inflammation (P=0.008, WTD: 95% CI: 1.4- 2.3; WTD+AA: 95% CI: 0.8- 1.5) and synovial lining thickness (WTD: 95% CI: 3.0-4.6, WTD+AA: 95% CI: 2.1-3.2) during early-stage collagenase-induced OA. Serum levels of S100A8/A9, MCP-1 and KC were significantly reduced after cholesterol-lowering treatment (P=0.0005, 95% CI:-46.0 to-12.0; P=2.8×10-10, 95% CI:-398.3 to-152.1; P=2.1×10-9,-66.8 to-30.4, respectively). However, this reduction did not reduce OA pathology, determined by ectopic bone formation, subchondral bone sclerosis and cartilage damage at end-stage disease. This study shows that intensive cholesterol-lowering treatment reduces joint inflammation after induction of collagenase-induced OA, but this did not reduce end stage pathology in female mice.

Genetics, Safety, Cost-Effectiveness, and Accessibility of Injectable Lipid-Lowering Agents: A Narrative Review.

Cardiovascular disease causes significant personal, financial, and societal burden and is a major cause of mortality and morbidity globally. Dyslipidemia has proven to be a major factor that contributes to its increased incidence; thus, since a long time, low-density lipoprotein cholesterol-lowering therapies have been employed to reduce coronary artery disease-associated mortality. The first-line therapy for hyperlipidemia and dyslipidemia is statins. Evidence showed that statins decrease the level of LDL-C resulting in a lower risk of CVD (20-25% for every decrease of 1 mmol/L). However, due to statin intolerance in some patients and despite using maximal doses, they have not been successful in lowering cardiovascular-associated mortality. Moreover, bococizumab was recently suspended due to its higher immunogenicity with time, resulting in less efficacy with long-term use. Alternatives to statins are PCSK9 inhibitors which are administered subcutaneously every two or four weeks. They are injectables with considerable lipid-lowering properties. This narrative review discusses their genetics, safety, tolerability, and cost-effectiveness. It also quantifies their benefit in certain subgroups by analyzing the findings from recent randomized clinical trials. Current data from phase 2 and 3 trials (ORION, ODYSSEY, and FOURIER) suggest a favorable profile for evolocumab, alirocumab, and inclisiran with minimal tolerable side effects and superior efficacy in statin-intolerant patients. Their cost-effectiveness has not yet been established clearly, but future outcomes seem promising.

Familial hypercholesterolaemia in pregnancy: Australian case series and review.

Familial hypercholesterolaemia (FH) is associated with a significant increase in the risk of premature coronary artery disease. Pregnancy is likely a vulnerable time for atherosclerosis progression, with a physiological rise in low-density lipoprotein cholesterol (LDL-C) further exaggerated by the discontinuation of cholesterol-lowering therapy. A retrospective review was undertaken of 13 women with familial hypercholesterolemia who were managed during pregnancy between 2007 and 2021 by a multidisciplinary team following individualised risk assessment. Overall, pregnancy outcomes were good, with no maternal or fetal complications, including congenital abnormalities, maternal cardiac events or hypertensive complications. Loss of statin treatment time ranged between 12months and 3.5 years resulting from the accumulation of the preconception, pregnancy and lactation periods and was magnified in women having more than one pregnancy. Of seven women treated with cholestyramine, one developed abnormal liver function with an elevated international normalisation ratio which was corrected with vitamin K. Pregnancy is associated with prolonged cessation of cholesterol-lowering therapy, a concern with respect to the risk of coronary artery disease in FH. Continuation of statin therapy up to conception and even during pregnancy in patients at higher risk of cardiovascular disease may be justified, especially with increasing evidence supporting the safety of statin therapy during pregnancy. However, more long-term maternal and fetal data are required for the routine use of statins during pregnancy. Guideline-informed models of care covering family planning and pregnancy should be implemented for all women with FH.

Australian Atherosclerosis Society Position Statement on Lipoprotein(a): Clinical and Implementation Recommendations.

This position statement provides guidance to cardiologists and related specialists on the management of adult patients with elevated lipoprotein(a) [Lp(a)]. Elevated Lp(a) is an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). While circulating Lp(a) levels are largely determined by ancestry, they are also influenced by ethnicity, hormones, renal function, and acute inflammatory events, such that measurement should be done after accounting for these factors. Further, circulating Lp(a) concentrations should be estimated using an apo(a)-isoform independent assay that employs appropriate calibrators and reports the results in molar units (nmol/L). Selective screening strategies of high-risk patients are recommended, but universal screening of the population is currently not advised. Testing for elevated Lp(a) is recommended in all patients with premature ASCVD and those considered to be at intermediate-to-high risk of ASCVD. Elevated Lp(a) should be employed to assess and stratify risk and to enable a decision on initiation or intensification of preventative treatments, such as cholesterol lowering therapy. In adult patients with elevated Lp(a) at intermediate-to-high risk of ASCVD, absolute risk should be reduced by addressing all modifiable behavioural, lifestyle, psychosocial and clinical risk factors, including maximising cholesterol-lowering with statin and ezetimibe and, where appropriate, PCSK9 inhibitors. Apheresis should be considered in patients with progressive ASCVD. New ribonucleic acid (RNA)-based therapies which directly lower Lp(a) are undergoing clinical trials.

The Management of Hypercholesterolemia in Patients with Neuromuscular Disorder.

We describe and discuss the safety of statins and non-statin drugs in neuromuscular disorders (NMDs). We also propose a pragmatic model of care for the management of such cases. Patients with both NMD and hypercholesterolemia may be particularly disadvantaged owing to the toxic effects of cholesterol-lowering therapy and the inability to take medication. Specifically, the management of hypercholesterolemia in patients with NMD is complicated by the increased risk of statin-related myotoxicity and concerns that statins may aggravate or possibly induce the onset of a specific NMD. The most severe form of statin-related myotoxicity is immune-mediated necrotizing myopathy. Management of hypercholesterolemia in patients with NMDs include treating modifiable factors, consideration of toxicity risk of statin, use of non-statin lipid lowering agents, noting possible drug interactions, and careful monitoring.

INFLUENCE OF ROSUVASTATIN ON VASCULAR ENDOTHELIUM FUNCTIONAL STATE AND SYSTEMIC INFLAMMATION IN PATIENTS WITH ISCHEMIC HEART DISEASE AND DIABETES MELLITUS

Purpose of the study. The goal of the present study was to evaluate the effect of low dosed statins (rosuvastatin 10 mg/day) on the state of lipid and carbohydrate metabolism, insulin levels, vascular endothelial function, and markers of systemic inflammation in patients with ischemic heart disease in combination with diabetes mellitus.
 Materials and research methods. We examined 83 patients with ischemic heart disease and type 2 diabetes mellitus aged 44 to 78 years (mean age was (56,8 ± 3,4) years). For all patients, the fasting glucose level was determined, the HOMA index, the levels of total cholesterol, low density lipoproteins, very low density lipoproteins, high density lipoproteins and triglycerides in the blood, the concentration of C-reactive protein, and the content of pro-inflammatory cytokines in the blood serum were calculated. To study the function of the endothelium, dopplerography of the brachial artery was used according to the D.S. Celermajer. All patients received IHD therapy according to generally accepted standards. The drugs were used against the background of stable oral hypoglycemic therapy. As cholesterol-lowering therapy, rosuvastatin was prescribed at a dose of 10 mg/day for 3 months.
 Results. During the study, it was noted that in patients with coronary artery disease in combination with type 2 diabetes mellitus on the background of hyperand dyslipidemia, elevated levels of insulin and glucose, dysfunction of the vascular endothelium was revealed. Vascular endothelial dysfunction had a close correlation with markers of systemic inflammation, which was exacerbated by the presence of insulin resistance. While taking rosuvastatin at a dose of 10 mg/day, in addition to a sufficient lipid-correcting effect, there was a decrease in the level of IR, activity of systemic inflammation and improvement in the function of the vascular endothelium, which ensures the correction of additional risk factors in patients with coronary artery disease in combination with type 2 diabetes.
 Conclusions. In patients with ischemic heart disease in combination with type 2 diabetes mellitus on the background of hyperand dyslipidemia, elevated levels of insulin and glucose, dysfunction of the vascular endothelium was revealed. Dysfunction of the vascular endothelium is closely correlated with markers of systemic inflammation, which is exacerbated by the presence of insulin resistance. Against the background of taking rosuvastatin at a dose of 10 mg/day, in addition to a sufficient lipid-correcting effect, a decrease in the level of IR, activity of systemic inflammation and an improvement in the function of the vascular endothelium were noted, which ensures the correction of additional risk factors in patients with coronary artery disease in combination with type 2 diabetes.

Dyslipidemia and the preventive potential in the Greenlandic population

BackgroundLow-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for development of cardiovascular diseases. Based on available clinical data, we aimed to investigate the plasma lipid profile in the Greenlandic population, the proportion on cholesterol-lowering treatment and the adherence to local indications for cholesterol-lowering therapy. MethodsThis is an observational cross-sectional study of the adult (≥21 years) Greenlandic population with focus on clinically determined lipid levels from 2017 to early 2022. We investigated levels of dyslipidemia and assessed cholesterol-lowering medication usage in individuals with an indication according to current Greenlandic guidelines, which include a) LDL-C >5 mmol/l, b) diabetes, c) diagnosed atherosclerotic disease and 4) a SCORE2 >7.5%. ResultsIn the adult Greenlandic population of 40,565 individuals a lipid profile was available in 13,895 with a mean LDL-C of 3.0 mmol/L and 976 (7%) had a LDL-C >5 mmol/l. One or more indications for cholesterol-lowering medication was present in 3988 individuals and a total of 5464 adult Greenlanders either fulfilled local criteria for statin therapy or received a statin (some without current indication) and among these, 2232 (41%) individuals received no statin. ConclusionThese findings indicate that clinically significant dyslipidemia is common in the adult Greenlandic population and that the cardiovascular preventive potential of cholesterol-lowering therapy is currently underutilized.

Familial Hypercholesterolemia Patients with COVID-19-Effective Cholesterol-Lowering Therapy is Urgent both during and after Infection.

Heterozygous familial hypercholesterolemia (HeFH) patients are the prime example of subjects who are at high risk for both acute myocardial infarction (AMI) and ischemic stroke during, and post, SARS-CoV-2 infection. HeFH per se, if left untreated, results in premature clinical atherosclerosis often presenting in the fourth or fifth decade of life. The other concern in HeFH is endothelial dysfunction which is already evident from early childhood. In untreated HeFH patients, the severe hypercholesterolemia causes endothelial dysfunction from an early age, and as a result thereof, atherosclerotic lesions develop prematurely, particularly in the coronary arteries, and result in further endothelial dysfunction and inflammation in these critical segments of the arterial tree. As the pre-existing endothelial dysfunction in HeFH patients is most likely sensitive to further direct and indirect SARS-CoV-2 virus-dependent damage, we can infer that HeFH serves as an example of a comorbidity that predicts a poorer prognosis with COVID-19 infection. Indeed, a large US national database study showed that patients diagnosed with HeFH and SARS-CoV-2 infection had significantly increased Annualized Incidence Density Rates (AIDRs) of AMI when compared to matched HeFH controls not having been diagnosed with SARS-CoV-2 infection. Effective cholesterol lowering is essential for the prevention, or at least alleviation, of the detrimental effects of SARS-CoV-2 infection among HeFH patients. Due to the pre-existing subclinical or even clinical atherosclerotic cardiovascular disease in subjects with HeFH, cholesterol-lowering treatment needs to be continued or, better still, intensified during, and for an extended period post, SARS-CoV-2 infection.

Comparison of measured LDL cholesterol with calculated LDL-cholesterol using the Friedewald and Martin-Hopkins formulae in diabetic adults at Charlotte Maxeke Johannesburg Academic Hospital/NHLS Laboratory.

The National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) and the European Society of Cardiology recommend using low-density lipoprotein cholesterol (LDL-C) as a treatment target for cholesterol lowering therapy. The Friedewald formula underestimates LDL-C in non-fasted and hypertriglyceridemia patients. This study aimed to compare measured LDL-C to calculated LDL-C in diabetic patients using the Friedewald and Martin-Hopkins formulae. The data of 1 247 adult diabetes patients were retrospectively evaluated, and included triglycerides (TG), LDL-C, total cholesterol, and high-density lipoprotein cholesterol that were measured on the Roche Cobas® c702. Passing-Bablok regression analysis was used to determine the degree of agreement between measured LDL-C and calculated LDL-C using both formulae. The Bland-Altman plots were used to assess the bias at medical decision limits based on the 2021 European Society of Cardiology (ESC) guidelines on cardiovascular disease prevention in clinical practice. Both formulae showed a good linear relationship against measured LDL-C. However, the Martin-Hopkins formula outperformed the Friedewald formula at LDL-C treatment target <1.4mmol/L. The Friedewald formula and the Martin-Hopkins formula had 14.9% and 10.9% mean positive bias, respectively. At TG-C ≥1.7 mmol/L, the Martin-Hopkins formula had a lower mean positive bias of 4.2% (95% CI 3.0-5.5) compared to the Friedewald formula, which had a mean positive bias of 21.8% (95% CI 19.9-23), which was higher than the NCEP ATP III recommended total allowable limit of 12%. The Martin-Hopkins formula performed better than the Friedewald formula at LDL-C of 1.4 mmol/L and showed the least positive bias in patients with hypertriglyceridemia.

Lipid Modification to Reduce Cardiovascular Risk in Secondary Prevention Patients with Special Emphasis on PCSK9 Inhibitor Requirement: An Analysis Based on Delphi Panel Approach.

The aim of this study is to analyze the low-density lipoprotein cholesterol-lowering therapies in secondary prevention patients by analyzing their plasma low-density lipoprotein cholesterol levels, current treatment, considering their inadequate response to medications (as defined in current guidelines), and the requirement for a protein convertase subtilisin/kexin type 9 inhibitor. Delphi panel is used to seek expert consensus of experienced 12 cardiologists. A questionnaire consisting of 6 main questions is used to reflect the opinion of the expert panelists on the practices of low-density lipoprotein cholesterol-lowering therapies of patients with high and very high cardiovascular risk. Patients with atherosclerotic cardiovascular disease are covered in this present analysis. According to expert opinion data, 18.6% of the patient population with atherosclerotic cardiovascular disease is estimated to have experienced recurrent vascular events. The current treatment of the patient population is 39.7% on high dose, 36.9% on low/moderate dose of statin, 13.1% on maximum tolerated dose statin+ezetimibe, and 1.2% on maximum tolerated dose statin+ezetimibe+protein convertase subtilisin/kexin type 9 inhibitor. The percentage of atherosclerotic cardiovascular disease patients with inadequate treatment response is estimated to be 20.2% in those using "maximum tolerated dose statin+ezetimibe." The proportion of patients who will need to be treated with a protein convertase subtilisin/kexin type 9 inhibitor increases as their low-density lipoprotein cholesterol levels rises from 9.1% in 70-99 mg/dL to 50.8% in ≥160 mg/dL for these patients. According to expert opinion, although a substantial proportion of patients with secondary prevention have not achieved low-density lipoprotein cholesterol goals, the use of protein convertase subtilisin/kexin type 9 inhibitors is very low. Since the questionnaire subject to panel discussion did not include any question elaborating the issue, the discrepancy between the recommendation of the related guidelines and Turkish practice needs further studies for the explanation.

IL-1β inhibition combined with cholesterol-lowering therapies decreases synovial lining thickness and spontaneous cartilage degeneration in a humanized dyslipidemia mouse model

Both systemic inflammation and dyslipidemia contribute to osteoarthritis (OA) development and have been suggested as a possible link between metabolic disease and OA development. Recently, the CANTOS trial showed a reduction in knee and hip replacements after inhibition of IL-1β in patients with a history of cardiovascular disease and high inflammatory risk. In this light, we investigated whether inhibition of IL-1β combined with cholesterol-lowering therapies can reduce OA development in dyslipidemic APOE∗3Leiden mice under pro-inflammatory dietary conditions. Female ApoE3∗Leiden mice were fed a cholesterol-supplemented Western-Type diet (WTD) for 38 weeks. After 14 weeks, cholesterol-lowering and anti-inflammatory treatments were started. Treatments included atorvastatin alone or with an anti-IL1β antibody, and atorvastatin combined with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor alirocumab without or with the anti-IL1β antibody. Knee joints were analyzed for cartilage degradation, synovial inflammation and ectopic bone formation using histology at end point. Cholesterol-lowering treatment successfully decreased systemic inflammation in dyslipidemic mice, which was not further affected by inhibition of IL-1β. Synovial thickening and cartilage degeneration were significantly decreased in mice that received cholesterol-lowering treatment combined with inhibition of IL-1β (P<0.01, P<0.05, respectively) compared to mice fed a WTD alone. Ectopic bone formation was comparable between all groups. These results indicate that inhibition of IL-1β combined with cholesterol-lowering therapy diminishes synovial thickening and cartilage degeneration in mice and may imply that this combination therapy could be beneficial in patients with metabolic inflammation.

Abstract 11473: An EHR-Based Machine Learning Model Predicts Myocardial Infarction Better Than an ECG-Based Machine Learning Model and the Pooled Cohort Equations

Introduction: Patients at high risk for myocardial infarction (MI) benefit from treatments designed for primary prevention, especially cholesterol lowering therapy. The pooled cohort equations (PCE) are the most commonly used risk predictor for future MI but show only modest performance. Hypothesis: Electronic health record (EHR)-based, and ECG-based machine learning models are better at predicting MI as compared toPCE. Methods: We retrospectively included all patients (age 40-79) with clinical encounters in Geisinger, having at least 1 clinically acquired ECG and no prior history of MI. Incident MI within 10 years of an index ECG was identified. The ability of 2 machine learning models to predict MI were compared to the PCE: 1) an XGBoost model with EHR data (age, sex, race, smoking history, vitals, 24 lab tests) as input features; and 2) a deep neural network (DNN) that used ECG traces, age, and sex as inputs. Models were compared based on area under the receiver operating characteristic curve (AUROC). Results: A total of 103,933 ECGs from 34,932 patients had sufficient follow-up, 21% of ECGs were followed by an MI event within 10 years. The EHR-based XGBoost model had the best performance (AUROC 81%) in comparison with both the ECG-based DNN model (AUROC 68%) and the PCE (AUROC 72%). 9% of the total encounters were predicted to be ‘high risk’ by the EHR-based model and not by the pooled cohort equations. In that subgroup, 60% of patients were not on a statin and the 10-year MI event rate was 26%. 20% of encounters were predicted to be ‘high risk’ by the PCE and not by the EHR-based model. The event rate in that subgroup was 12%. Conclusions: An EHR-based XGBoost model, but not an ECG-based DNN, is superior to the PCE in predicting future MI. Patients identified as high risk by the EHR-based model but missed by the PCE, have a high rate of future MI. Statin use in that group is low, suggesting ample opportunity for intervention.

Advances and Applications of Polygenic Scores for Coronary Artery Disease.

Polygenic scores quantify inherited risk by integrating information from many common sites of DNA variation into a single number. Rapid increases in the scale of genetic association studies and new statistical algorithms have enabled development of polygenic scores that meaningfully measure-as early as birth-risk of coronary artery disease. These newer-generation polygenic scores identify up to 8% of the population with triple the normal risk based on genetic variation alone, and these individuals cannot be identified on the basis of family history or clinical risk factors alone. For those identified with increased genetic risk, evidence supports risk reduction with at least two interventions, adherence to a healthy lifestyle and cholesterol-lowering therapies, that can substantially reduce risk. Alongside considerable enthusiasm for the potential of polygenic risk estimation to enable a new era of preventive clinical medicine is recognition of a need for ongoing research into how best to ensure equitable performance across diverse ancestries, how and in whom to assess the scores in clinical practice, as well as randomized trials to confirm clinical utility.

Global Trends in the Epidemiology and Management of Dyslipidemia

Dyslipidemia, especially a circulating non-optimal level of cholesterol, is one of the most important risk factors for atherosclerotic cardiovascular disease (ASCVD), which accounts for the most deaths worldwide. Maintaining a healthy level of blood cholesterol is an important prevention strategy for ASCVD, through lifestyle intervention or cholesterol-lowering therapy. Over the past three decades, the epidemiology and management of dyslipidemia has changed greatly in many countries. Therefore, it is necessary to understand the current epidemiologic features of dyslipidemia and challenges from a global perspective.

Distribution of cardiovascular disease risk according to SCORE2 and potential need for cholesterol and blood pressure lowering therapy in apparently healthy middle-aged individuals

Abstract Background The 2021 European Society of Cardiology (ESC) prevention guidelines recommend the Systemic Coronary Risk Estimation 2 algorithm (SCORE2) to estimate the 10-year risk of cardiovascular disease (CVD) events to guide pharmacological treatment for primary prevention in apparently healthy individuals aged 40–69 years. Purpose To assess the distribution of CVD risk according to SCORE2 and the proportion of individuals who could be eligible for pharmacological treatment of blood cholesterol and blood pressure in an apparently healthy middle-aged population in Sweden. Methods We used data from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) which used population registers to randomly recruit individuals aged 50–64 years at six Swedish study sites. Information was collected from the study participants through clinical examinations, national registries, and questionnaires. We excluded individuals with previously known atherosclerotic CVD, diabetes mellitus, or chronic kidney disease with eGFR &amp;lt;60 mL/min/1.73 m2. The SCORE2 algorithm designed for countries with moderate baseline CVD risk was used to categorize study participants' 10-year CVD risk as low-moderate (&amp;lt;5% risk); high (5-&amp;lt;10% risk); and very-high (≥10% risk). The proportions of the population who could be eligible, according to the 2021 ESC prevention guidelines, for pharmacological treatment of LDL-cholesterol (LDL-C) were assessed. Treatment thresholds for LDL-C according to SCORE2 risk were ≥1.8 mmol/L (high risk) and ≥1.4 mmol/L (very-high risk). Treatment threshold for hypertension was defined as a blood pressure ≥140/90 mmHg regardless of CVD risk. Results SCAPIS included 30,082 individuals. After exclusion criteria were applied 26,877 individuals remained (median age 57.2 years; 52.8% women). The median 10-year risk of CVD according to SCORE2 was 5.0 (interquartile range 3.0, 7.0) %. In total, 47.5% were classified as low-moderate risk, 45.9% as high risk, and 6.6% as very-high risk, with men having higher risk than women (figure). Almost all of those with high and very-high risk had LDL-C levels above the treatment thresholds. As such, according to the guidelines, lipid-lowering treatment should be considered (high risk) or was generally recommended (very-high risk) in 51.7% of the total population (Figure 1). The proportion of individuals with blood pressure ≥140/90 mmHg was 21.9%. The self-reported use of lipid-lowering therapy among low-moderate, high risk, and very-high risk individuals was 3.1%, 6.9%, and 6.3%, respectively. The use of blood pressure lowering therapy was 13.1% for those with blood pressure &amp;lt;140/80 mmHg and 29.2% for those ≥140/90 mmHg. Conclusions In this population-based study of nearly 27,000 apparently healthy middle-aged individuals in Sweden, around half of the individuals could be eligible for LDL-C-lowering therapy and around one in five could be eligible for antihypertensive therapy according to the 2021 ESC prevention guidelines. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): SCAPIS funding: The Swedish Heart-Lung Foundation and Knut and Alice Wallenberg Foundation.

Abstract 113: Statins, But Not Pcsk9 Inhibitors, Reduce The Adipokine Chemerin In Familial Hypercholesterolemia: Focus On Lipoprotein Subfractions.

Background: Familial hypercholesterolemia (FH) is characterized by severe elevations in circulating LDL-cholesterol, and an increase in the risk of dyslipidemia-related cardiovascular disease (CVD). Chemerin, as a newly identified adipokine, is considered as an additional risk factor for CVD. Here we investigated whether it can be modified by cholesterol-lowering therapy. Methods: Lipoprotein subfractions were isolated by density gradient ultracentrifugation. Lipids and chemerin concentrations were determined both before and after cholesterol lowering with either a statin (atorvastatin, simvastatin, rosuvastatin, or fluvastatin) or a PCSK9 inhibitor (PCSK9i; alirocumab or evolocumab). Results: At baseline chemerin levels were 113±46 (statin group) and 95±44 (PCSK9i group) ng/ml, while triglyceride (TG) levels were 1.9±1.6 and 2.6±1.7 mmol/ml, high-density lipoprotein cholesterol (HDL-c) levels were 1.3±0.4 and 1.2±0.4 mmol/ml, and low-density lipoprotein cholesterol (LDL-c) levels were 5.7±1.5 and 4.9±1.4 mmol/ml (P=ns for difference between 2 groups). Chemerin correlated positively with triglycerides (r=0.45, P&lt;0.005) and negatively with HDL-c (r=-0.33, P&lt;0.01). Both statins and PCSK9i reduced LDL-c (by 41 and 62%, P&lt;0.0001), triglycerides (by 13 and 19%, P&lt;0.01), and increased HDL-c (by 8 and 23%, P&lt;0.01), but only statins additionally reduced chemerin (by 35%, P&lt;0.005). The lipoprotein subfraction profile revealed that chemerin accumulated particularly in the HDL3 fraction (containing &gt;60% of all chemerin in lipoprotein subfractions), with approximately 30% being present in the HDL2 fraction, and approximately 3% in the LDL fraction. Statins reduced HDL3-c and HDL3-TG, and the level of chemerin bound to all subfractions. PCSK9i reduced HDL3-c but did not affect HDL3-TG or the level of chemerin bound to HDL3 and HDL2. Conclusions: Circulating chemerin occurs in different lipoprotein subfractions, accumulating particularly in the HDL3 fraction. Statins, but not PCSK9i, lowers chemerin, possibly by interfering with its levels across lipoprotein subfractions. This may represent a novel cardiovascular protective function of statins.

Linking cellular lipid metabolism profiles to the outcomes of cholesterol-lowering therapy in a general population cohort study

Background and Aims : Alterations in cellular lipid metabolism are linked to differential treatment outcomes in familial hypercholesterolemia patients. However, whether similar effects exist in the general population is not known.