Low-density Lipoprotein Cholesterol Reduction Research Articles

The Effect Of Weight Loss With Lifestyle Changes On LDL Cholesterol: Retrospective Cohort Study

Aim: This study aimed to investigate the rate of decrease in lipid levels with effective lifestyle changes (LC) and the minimum body weight loss necessary for effective lipid reduction in obese patients. Method: The study is a retrospective cohort study. The study included 71 patients who were followed up in the obesity clinic, who were diagnosed with hyperlipidemia but did not use any hyperlipidemia treatment. The patients' high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglyceride, body fat ratio and mass, body mass index (BMI), height and weight information were recorded at the first visit and the 6th month. In our study, patients were divided into two groups (based on the weight loss rates in the 6-month follow-up) those who lost less than 10% of their previous weight and those who lost 10% or more weight and their lipid parameters were compared. Results: LDL-C reduction rates of patients classified according to their weight loss rates were found to be statistically significantly (p=0.011) higher in those with 10% or more weight loss than (group 1=18.48%) in those with less than 10% weight loss (group 2=13.04%). Total cholesterol reduction rates were also significantly (p=0.015) higher in the 1st group than in the 2nd group. According to the findings of our study, at least 10% weight loss is required to decrease total cholesterol and LDL-C significantly. Conclusion: Implementation of primary and secondary prevention strategies to reduce the risk of cardiovascular disease is important in the context of primary care. To reach the targeted LDL-C values, the weight monitoring of obese patients should be considered, and the importance of losing at least 10% of weight as one of the first steps should be emphasized.

Rapid lipid-lowering response in two cases of autosomal recessive hypercholesterolemia

BackgroundAutosomal recessive hypercholesterolemia (ARH) is an ultrarare dyslipidemia caused by variants in the LDLRAP1 gene. Clinically, this condition is indistinguishable from other homozygous familial hypercholesterolemia (HoFH). CaseWe present the cases of two siblings diagnosed with ARH caused by LDLRAP1 gene c.617-14C>A splicing homozygous variant. Over a five-year treatment period, the older sibling experienced an 81 % reduction in low-density lipoprotein cholesterol (LDL-C) levels with the maximal dose of pitavastatin plus ezetimibe, while the younger sibling achieved a 75 % reduction. After three sessions, the older brother no longer required LDL apheresis, and the sibling never had LDL apheresis. ConclusionOur findings demonstrate a rapid and significant response to lipid-lowering therapy (LLT) in patients with ARH caused by c.617-14C>A splicing VUS variant, a condition that mimics HoFH at diagnosis. Long-term follow-up studies in large pediatric cohorts of ARH patients treated with pitavastatin plus ezetimibe from childhood are necessary to better define the risk of cardiovascular disease (CVD) development.

Impact of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 Probiotic Supplementation on the Gut Microbiome of Hypercholesterolemia Patients: A Randomized Controlled Trial.

Probiotics have shown potential in managing hypercholesterolemia and related metabolic conditions. This study evaluated the effects of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 on the gut microbiome and metabolic health in patients with hypercholesterolemia, and was registered in the Thai Clinical Trial Registry (TCTR 20220917002). In a randomized, double-blind, placebo-controlled trial, 22 hypercholesterolemic participants received either the probiotic or a placebo daily for 90 days. Fecal samples collected before and after the intervention revealed significant microbiome changes, including a decrease in Subdoligranulum, linked to rheumatoid arthritis, and an increase in Flavonifractor, known for its anti-inflammatory properties. Additionally, the probiotic group exhibited a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels. These findings suggest that L. paracasei TISTR 2593 can modulate the gut microbiome and improve metabolic health, warranting further investigation into its mechanisms and long-term benefits.

Characteristics of Patients With Atherosclerotic Cardiovascular Disease in Belgium and Current Treatment Patterns for the Management of Elevated LDL-C Levels.

Dyslipidemia remains the major cause of atherosclerotic cardiovascular disease (ASCVD). Lipid management in patients with increased cardiovascular (CV) risk needs improvement across Europe, and data gaps are noticeable at the country level. We described the current treatment landscape in Belgium, hypothesizing that lipid management in patients with ASCVD remains inadequate and aiming to understand the reasons. Using data from an anonymized primary care database in Belgium derived from 494 750 individuals, we identified those with any CV risk factor between November 2019 and October 2022 and described the clinical features of patients with ASCVD. The main outcomes were the proportion of patients (i) receiving lipid-lowering therapies (LLTs), (ii) per low-density lipoprotein cholesterol (LDL-C) threshold, stratified per LLT, (iii) reaching the 2021 ESC recommended LDL-C goals, and (iv) LDL-C reduction per type of LLT was also determined. Among 40 888 patients with very high CV risk, 24 859 had established ASCVD. Most patients with ASCVD were either receiving monotherapy (59.6%) or had no documented LLT (25.1%). Further, 64.2% of those with no documented LLT exhibited LDL-C levels ≥ 100 mg/dL. Among common treatment options, one of the greatest improvements in LDL-C levels was achieved with combination therapy of statin and ezetimibe, reducing LDL-C levels by 41.5% (p < 0.0001). Yet, in this group, 24.8% of patients had still LDL-C levels ≥ 100 mg/dL and only 20.7% were at goal. Our study emphasizes the importance of developing strategies to help patients achieve their LDL-C goals, with a focus on supporting the implementation of combination LLT in routine clinical practice.

LDL-cholesterol goal achievement and self-reported medication adherence: insights from the JET-LDL registry

In patients with recent acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dl. Despite the widespread use of different potent lipid-lowering therapies (LLT), this goal is not always achieved, often due to poor medication adherence. In this prespecified subanalysis of the JET-LDL registry, we sought to evaluate the relationship between LDL-C targets achievement and LLT adherence in a cohort of patients hospitalized for ACS. Patients self-reported medication adherence was assessed using the Morisky Medication Adherence Scale (MMAS) at 3-months follow-up. Depending on the score obtained, the population was divided into two groups: high adherence (HA, MMAS≥6) vs low adherence (LA, MMAS<6). The occurrence of the primary-endpoint (LDL-C reduction >50% from baseline or level <55 mg/dl at 1-month) was compared between the two groups. 963 patients were included in the present analysis; in 277 cases (28.7%) a MMAS score <6 was reported (LA-group), while in the other 686 (71.3%) the score obtained was ≥6 (HA-group). No difference between the two groups was observed regarding LDL-C levels at admission and LLT prescribed at discharge. At 1-month, primary-endpoint occurred in 62.5% of cases, with a statistically significant difference between the two groups (LA 60% vs HA 65%, p-value 0.034). At multivariate logistic regression analysis, LA was identified as an independent predictor of not achieving the primary-endpoint (OR 0.48 [0.39-0.85], p-value 0.006). In conclusion, in a real-world cohort of patients with ACS, low medication adherence to LLT was a common event (28.7%), having a negative impact on LDL-C goal achievement.

Efficacy and safety of statins, ezetimibe and statins-ezetimibe therapies for children and adolescents with heterozygous familial hypercholesterolaemia: Systematic review, pairwise and network meta-analyses of randomised controlled trials

Background and aimsStatins, ezetimibe and statins-ezetimibe combination therapy are recommended lipid-lowering therapies (LLTs) in children with heterozygous familial hypercholesterolaemia (HeFH). However, their relative effectiveness is not well understood. We aimed to compare the safety and efficacy of these therapies using direct and indirect comparisons. MethodsWe conducted systematic review, pairwise and network meta-analyses (NMAs) of randomised-controlled trials (RCTs) of statins, ezetimibe and statins-ezetimibe combination therapy in people <18 years with HeFH. Comprehensive bibliographic searches were conducted in December 2022, and a Medline update in January 2024. NMA models accounted for drug class, statin type and dosage. ResultsThirteen RCTs were included (n = 1649, median age 13 years, follow-up 6 weeks-2 years). All LLTs reduced low-density lipoprotein cholesterol (LDL-C) and total cholesterol; statins led to increases in high-density lipoprotein cholesterol and reductions in triglycerides. Statins reduced LDL-C by 33.61 % against placebo (95 % CI 27.58 to 39.63, I2 = 83 %). Adding ezetimibe to statins reduced LDL-C by an additional 15.85 % (95 % CI 11.91 to 19.79). NMAs showed intermediate-dose statins reduced LDL-C by an additional 4.77 % compared with lower-doses statins (95 % CrI −11.22 to 1.05); higher-dose statins and intermediate-dose statins + ezetimibe may be similarly effective and are probably superior to ezetimibe, intermediate-and lower-dose statins. There was no evidence of differences in maturation, safety or tolerability between LLTs and placebo. ConclusionsStatins, ezetimibe and statins-ezetimibe are all effective treatments for children with HeFH, but the magnitude of LDL-C reductions varies and may depend on treatment dosage and combination. No safety or tolerability issues were found. Longer-term safety and effectiveness are uncertain.

Effectiveness of Omega-3 Polyunsaturated Fatty Acids in Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder characterized by excessive hepatic fat accumulation without alcohol intake. It can progress to non-alcoholic steatohepatitis, increasing the risk of cirrhosis and liver failure. This study aims to evaluate the efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in treating NAFLD. A systematic review and meta-analysis was conducted including studies published from January 2018 to June 2023. Databases searched included PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Inclusion criteria comprised randomized controlled trials and cohort studies involving human subjects or animal models with NAFLD. Data were extracted and analyzed to assess the impact of omega-3 PUFAs on liver fat, hepatic enzymes, and serum lipid profiles using RevMan 5.4. A total of 15 studies met the inclusion criteria. Omega-3 supplementation significantly decreased alanine aminotransferase (ALT) (mean difference = -2.12, 95% confidence interval (CI) = -3.36, -0.87) and aspartate aminotransferase (AST) (mean difference = -1.50, 95% CI = -2.59, -0.42). Gamma-glutamyl transferase levels showed a trend toward reduction (mean difference = -0.82, 95% CI = -1.66, 0.02). Serum lipid profiles improved significantly with reductions in triglycerides, low-density lipoprotein, and total cholesterol along with significant reductions in AST, ALT, and alkaline phosphatase in animal models. Omega-3 PUFAs appear to offer beneficial effects on liver enzymes, serum lipid profiles, and anthropometric indices in NAFLD patients. While their impact on liver fat content remains uncertain, omega-3 supplementation could serve as a valuable adjunct treatment for enhancing metabolic profiles and liver function in NAFLD patients.

Evolocumab (Repatha)

It is recommended that Repatha be reimbursed by public drug plans for the reduction of elevated low-density lipoprotein cholesterol (LDL-C) in adult patients with primary hyperlipidemia (atherosclerotic cardiovascular disease [ASCVD]) if certain conditions are met. Repatha should only be covered to treat patients with a recent acute coronary syndrome (ACS) event, defined as those who have been hospitalized for a heart attack or unstable angina in the past 52 weeks. Additionally, these are patients with an LDL-C level between 1.8 mmol/L and 2.2 mmol/L (inclusive) or a non–high-density lipoprotein cholesterol (non–HDL-C) level between 2.6 mmol/L and 2.9 mmol/L (inclusive) or an apolipoprotein B (ApoB) level between 0.7 g/L and 0.8 g/L (inclusive), despite receiving the highest dose of statin that can be tolerated and ezetimibe. Alternatively, these are patients with an LDL-C level greater than 2.2 mmol/L, a non–HDL-C greater than 2.9 mmol/L, or an ApoB greater than 0.8 g/L, despite receiving the highest dose of statin that can be tolerated, with or without ezetimibe. Repatha should only be reimbursed if prescribed by a cardiologist or internal medicine specialist with expertise in the post-ACS setting and if the cost of Repatha is reduced. Repatha should not be reimbursed for use in combination with other PCSK9 inhibitors.

LDL-Cholesterol-Lowering Effects of a Dietary Supplement Containing Onion and Garlic Extract Used in Healthy Volunteers.

Hypercholesterolemia plays a pivotal role in the development and progression of cardiovascular diseases, and its prevention seems to be a crucial healthcare strategy to ameliorate these conditions. Subjects with mild hypercholesterolemia are frequently advised against using cholesterol-lowering drugs due to potential side effects, with an emphasis instead on prioritizing dietary adjustments and lifestyle modifications as the primary strategy. In this context, the use of dietary supplements based on medicinal plants may be recommended as a complementary approach to managing elevated cholesterol levels. The aim of this study was to investigate the safety and potential therapeutic effectiveness of a standardized formulation containing extracts from garlic and onions in addressing the health concerns of individuals with slightly elevated cholesterol levels. A controlled, randomized, double-blind, two parallel-group study was conducted over 8 weeks, with clinical visits scheduled at baseline, weeks 2 and 4, as well as at the end of the study. The results revealed significant reductions in both low-density lipoprotein cholesterol and total cholesterol levels among participants who received the extract. Additionally, improvements in blood pressure, as well as in oxidative and inflammatory markers were observed, thus suggesting its potential as a valuable therapeutic intervention for managing mild hypercholesterolemia.

Randomized, open-label, study comparing efficacy and safety of lerodalcibep to inclisiran in patients with CVD or at high risk for CVD requiring additional LDL-cholesterol reduction

Randomized, open-label, study comparing efficacy and safety of lerodalcibep to inclisiran in patients with CVD or at high risk for CVD requiring additional LDL-cholesterol reduction

Clinical Considerations for HealthcareProvider-Administered Lipid-Lowering Medications.

Atherosclerotic cardiovascular disease (ASCVD), a leading cause of mortality and morbidity, is associated with a substantial healthcare and economic burden. Reduction of low-density lipoprotein cholesterol (LDL-C) to guideline-recommended goals is crucial in the prevention or management of ASCVD, particularly in those at high risk. Despite the availability of several effective lipid-lowering therapies (LLTs), up to 80% of patients with ASCVD do not reach evidence-based LDL-C goals. This nonattainment may be due to poor adherence to, and lack oftimely utilization of, LLTs driven by a range of variables, including polypharmacy, side effects, clinical inertia, costs, and access issues. Inclisiran was approved by the US Food and Drug Administration in 2021 as a novel, twice-yearly, healthcare provider (HCP)-administered LLT. In-office administration allows HCPs more control of drug acquisition, administration, and reimbursement, and may allow for more timely care and increased patient monitoring. In the USA, in-office administered drugs are considered a Medical Benefit and can be acquired and reimbursed using the "buy-and-bill" process. Buy-and-bill is a standard system for medication administration already established in multiple therapeutic areas, including oncology, vaccines, and allergy/immunology. Initiating in-office administration will involve new considerations for clinicians in the cardiovascular specialty, such as the implementation of new infrastructure and processes; however, it could ultimately increase treatment adherence and improve cardiovascular outcomes for patients with ASCVD. This article discusses the potential implications of buy-and-bill for the cardiology specialty and provides a practical guide to implementing HCP-administered specialty drugs in US clinical practice.

Is it possible to regress atherosclerotic lesions with long-term treatment with lipoprotein apheresis?

The article presents the up-to-date information on the effect of lipoprotein apheresis (LA) on atherosclerotic lesions. Some studies using modern diagnostic imaging techniques (such as intravascular ultrasound or magnetic resonance imaging) have clearly demonstrated plaque regression. Coronary angiography has also seen reversal or at least slow plaque progression. Plaque regression likely leads to a decrease in the incidence of atherosclerotic cardiovascular events (CVEs). However, this has not yet been fully proven. Recent data indicate that reduction in low-density lipoprotein cholesterol and lipoprotein(a) levels is not a major factor in reducing the incidence of atherosclerotic CVEs in patients undergoing extracorporeal treatment. The most significant risk factors in this case are older age and a greater CVE rate observed before the start of LA, as well as smoking. New studies using modern diagnostic imaging methods in patients receiving LA are necessary.

A UK multicentre audit of the management of patients with primary hypercholesterolaemia or mixed dyslipidaemia with bempedoic acid against published lipid-lowering treatment targets.

Bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, was introduced to UK practice via a pre-reimbursement access scheme for adults with primary hypercholesterolaemia or mixed dyslipidaemia who are at high risk of cardiovascular disease, in whom statins are either not tolerated or contraindicated, who have not achieved target cholesterol, despite being on ezetimibe therapy, and do not qualify for PCSK9 inhibitor treatment. This retrospective multicentre audit aimed to evaluate the achievement of lipid-lowering targets with bempedoic acid in UK patients based on recommendations in the Joint British Societies (JBS) guidelines for the prevention of cardiovascular disease. Pseudo-anonymized medical record data for 221 adults treated with bempedoic acid as part of the UK scheme were entered into a bespoke data collection tool at four UK hospitals. Patient demographics, clinical characteristics, treatment pathways and lipid assessment results (against JBS lipid-lowering targets) were collected against pre-specified criteria. Overall, 54% (99/184) of patients achieved the JBS2 audit standard (total cholesterol (TC) <5 mmol/L and low-density lipoprotein cholesterol (LDL-C) <3 mmol/L or ≥25% reduction in TC and ≥30% reduction in LDL-C) at 12 weeks post-initiation. At week 12, the mean absolute change in LDL-C was -1.0 mmol/L; the mean percentage reduction from baseline was 22.0%. Additionally, 52% (96/185) of patients had an LDL-C of <3 mmol/L and 10% (18/185) an LDL-C of <1.8 mmol/L at 12 weeks (as per JBS3). This audit highlights the role of bempedoic acid as part of combination therapy for a population with previously limited treatment options.

Anti-hyperlipidemic effects of 500 mg spilanthol (SA3X) supplementation in people with dyslipidemia- a randomized, parallel-group placebo-controlled trial.

Dyslipidemia is a critical risk factor for cardiovascular disease. This study investigated the impact of 500 mg of spilanthol (SA3X) supplementation on lipid profiles in men with dyslipidemia using a randomized, parallel-group, placebo-controlled design. A total of 279 male participants were randomly allocated to one of four groups: SA3X without exercise, placebo without exercise, SA3X with exercise, and placebo with exercise. After a one-month control period, participants received SA3X capsules or placebo for three months. The exercise groups undertook standardized weight-lifting exercises four times weekly. Lipid profiles, biochemical parameters, and anthropometric measurements were monitored throughout and after the intervention. Both SA3X groups exhibited significant reductions in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) compared to the placebo groups. By day 90, the SA3X-no-exercise group showed a 16.78 % decrease in TC, while the SA3X-plus-exercise group demonstrated a 52.87 % decrease compared to placebo. Significant reductions in TG and LDL-C were noted at days 60 and 90 (p=0.01 and p=0.03, respectively). The SA3X-plus-exercise group also exhibited decreased random blood sugar levels at days 60 and 90 compared to placebo-plus-exercise. Moreover, decreases in C-reactive protein, creatine kinase, and serum creatinine levels were observed. SA3X supplementation, particularly when combined with exercise, effectively improved lipid profiles and various health markers in men with dyslipidemia. Adverse events, primarily taste disturbance, were mild. These findings suggest SA3X may be a promising adjunctive therapy for managing dyslipidemia, emphasizing its potential cardiovascular health benefits and supporting further investigation. CTRI/2021/05/033694; May 2021.

Monoclonal Anti-PCSK9 Antibodies: Real-World Data.

Background: Real-world data on the use of lipid-lowering therapy (LLT) in clinical practice show that about 80% of (very) high-cardiovascular (CV)-risk patients disregard the 2019 European Society of Cardiology (ESC) Guidelines' recommendations on dyslipidemias. The availability of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9mAb) should reduce this gap. Our aim was to provide data on PCSK9mAb use in clinical practice, investigating the achievement of the ESC Guidelines' recommendations in the real world. Methods: Between April 2018 and December 2022, patients who started on PCSK9mAb therapy (140 mg of evolocumab or 75 mg or 150 mg of alirocumab, subcutaneous injection every 2 weeks) were included in a prospective registry. Our cohort consisted of 256 patients: 95 (37.1%) were women (mean age: 65.43 ± 11.12 yrs), 53 (20.7%) were at high CV risk, and 203 (79.3%) were at very high CV risk. Results: After one year of PCSK9mAb treatment, nearly 60% of patients demonstrated full adherence to the ESC Guidelines' recommendations, defined as achieving at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C) levels along with reaching LDL-C target levels (≤55 and ≤70 mg/dL for very high and high risk, respectively). Concomitant high-dose statin therapy emerged as the primary predictor of LDL-C target attainment. Heterozygous familial hypercholesterolemia (HeFH), statin intolerance, and female gender were associated with a significant lower probability of achieving LDL-C target levels. Conclusions: Our analysis confirms that PCSK9mAb treatment is safe and effective, enabling 60% of our cohort to fully achieve the LDL-C guideline recommendations. The use of high-intensity statins emerged as a significant predictor of efficacy. Conversely, familial hypercholesterolemia and female gender were identified as predictors of therapeutic failure. Hence, it is crucial to address disparities in cardiovascular disease prevention between genders and to enhance strategies for managing elevated LDL-C in HeFH patients.

The systemic impact of non-surgical treatment of peri-implantitis with or without adjunctive systemic metronidazole: Secondary analysis of a randomized clinical trial.

The aim of this study was to evaluate the systemic effect of non-surgical peri-implantitis treatment (NSPIT) with or without the administration of systemic metronidazole. In this secondary analysis from a previously published clinical trial (NCT03564301), peri-implantitis patients were randomized into two groups: test, receiving NSPIT plus 500 mg of oral systemic metronidazole three times a day for 7 days (n = 10); and control group, receiving NSPIT plus placebo (n = 11). Serum samples were obtained at baseline, 3 and 6 months after therapy to determine levels of inflammatory biomarkers, lipid fractions and complete blood counts. Both treatment modalities produced improvements in clinical and radiographic parameters. After 6 months from NSPIT, a substantial reduction in C-reactive protein (6.9 mg/dL; 95% CI: 3.7 to 9.9, p < .001) and low-density lipoprotein cholesterol (21.8 mg/dL; 95% CI: -6.9 to 50.5, p = .013) as well as a modest increase in neutrophils counts (0.4 × 103/μL; 95% CI: -0.4 to 1.1, p = .010) was observed in the control group while the test group showed a significant reduction of TNF-α (110.1; 95% CI: 38.9 to 181.4, p = .004). NSPIT showed a short-term beneficial systemic effect regardless of adjunctive use of systemic metronidazole.

Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study

Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. For the Spanish translation of the abstract see Supplementary Materials section.

Effects of high- versus low-intensity lipid-lowering treatment in patients undergoing serial coronary computed tomography angiography: results of the multi-center LOCATE study.

To evaluate the effects of lipid-lowering medications of different intensities on total, calcified, and non-calcified plaque volumes in patients undergoing serial cardiac computed tomography angiography (CCTA). Individuals with chronic coronary syndromes from 11 centers were included in a retrospective registry. Total, calcified, and non-calcified plaque volumes were quantified and the relative difference in plaque volumes between baseline and follow-up CCTA was calculated. The intensity of lipid-lowering treatment was designated as low, moderate, or high, based on current recommendations. Of 216 patients (mean age 63.1 ± 9.7years), undergoing serial CCTA (median timespan = 824.5 [IQR = 463.0-1323.0] days), 89 (41.2%) received no or low-intensity lipid-lowering medications, and 80 (37.0%) and 47 (21.8%) moderate- and high-intensity lipid-lowering agents, respectively. Progression of total and non-calcified plaque was attenuated in patients on moderate-/high- versus those on no/low-intensity treatment and arrested in patients treated with high-intensity statins or PCSK9 inhibitors (p < 0.001). Halted increase of non-calcified plaque was associated with LDL-cholesterol reduction (p < 0.001), whereas calcified plaque mass and Agatston score increased irrespective of the lipid-lowering treatment (p = NS). The intensity of lipid-lowering therapy robustly predicted attenuation of non-calcified plaque progression as a function of the time duration between the two CCTA scans, and this was independent of age and cardiovascular risk factors (HR = 3.83, 95% CI = 1.81-8.05, p < 0.001). The LOCATE multi-center observational study shows that progression of non-calcified plaques, which have been previously described as precursors of acute coronary syndromes, can be attenuated with moderate-intensity, and arrested with high-intensity lipid-lowering therapy. DRKS00031954.

PCSK9 Inhibitor with Statin Therapy for Intracranial Artery Stenosis ( PISTIAS): Rationale and design of a multicenter randomized controlled trial.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54-75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g. Evolocumab) on symptomatic intracranial atherosclerosis remains unexplored. To determine whether combining Evolocumab and statins achieves a more significant symptomatic intracranial plaque regression than statin therapy alone. With a sample size of 1000 subjects, a two-sided α of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden. This is an investigator-initiated multicenter, randomized, open-label, outcome assessor-blinded trial, evaluating the impact of combining Evolocumab and statins on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) were randomized 1:1 into two groups to receive either Evolocumab 140 mg every 2 weeks with statin therapy or statin therapy alone. The primary endpoint is the change in intracranial plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and at the end of the 24-week treatment period. This trial will explore whether more significant intracranial plaque regression is achievable with the treatment of combining Evolocumab and statins, providing information about efficacy and safety data. ChiCTR2300068868; https://www.chictr.org.cn/.

Recipe for Heart Health: A Randomized Crossover Trial on Cardiometabolic Effects of Extra Virgin Olive Oil Within a Whole-Food Plant-Based Vegan Diet.

Whole-food, plant-based vegan diets, low in oils, and Mediterranean diets, rich in extra virgin olive oil (EVOO), reduce cardiovascular disease risk factors. Optimal quantity of dietary fat, particularly EVOO, is unclear. In a randomized crossover trial with weekly cooking classes, adults with ≥5% cardiovascular disease risk followed a high (4 tablespoons/day) to low (<1 teaspoon/day) or low to high EVOO whole-food, plant-based diet for 4 weeks each, separated by a 1-week washout. The primary outcome was difference in low-density lipoprotein cholesterol (LDL-C) from baseline. Secondary measures were changes in additional cardiometabolic markers. Linear mixed models assessed changes from baseline between phases, with age, sex, and body weight change as covariates. In 40 participants, fat intake comprised 48% and 32% of energy during high and low EVOO phases, respectively. Both diets resulted in comparable reductions in LDL-C, total cholesterol, apolipoprotein B, high-density lipoprotein cholesterol, glucose, and high-sensitivity C-reactive protein (all P<0.05). With diet-sequence interactions for LDL-C, differences were detected between diets by diet order (mean±SEM high to low: Δ-12.7[5.9] mg/dL, P=0.04 versus low to high: Δ+15.8[6.8] mg/dL, P=0.02). Similarly, low to high order led to increased glucose, total cholesterol, and high-density lipoprotein cholesterol (all P<0.05). Over period 1, LDL-C reductions were -25.5(5.1) post-low versus -16.7(4.2) mg/dL post-high EVOO, P=0.162, which diminished over period 2. Both plant-based diet patterns improved cardiometabolic risk profiles compared with baseline diets, with more pronounced decreases in LDL-C after the low EVOO diet. Addition of EVOO after following a low intake pattern may impede further lipid reductions. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04828447.