Low-density Lipoprotein Cholesterol Levels In Patients Research Articles

Metformin-Induced Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition Further Decreases Low-Density Lipoprotein Cholesterol Following Statin Treatment in Patients With Coronary Artery Disease and Without Diabetes.

In vitro investigations have established metformin's capacity to downregulate proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, suggesting a potential beneficial effect on atherogenic lipoprotein particles when combined with metformin therapy. Our objective was to assess whether metformin could mitigate statin-induced adverse effects on PCSK9, thereby improving lipid profiles in patients with coronary artery disease (CAD) but without diabetes. Employing an open-label, placebo-controlled, randomized trial, we randomized patients with CAD but without diabetes into CLA (cholesterol-lowering agents alone: atorvastatin±ezetimibe, n = 38) and Met + CLA groups (metformin plus CLA, n = 33) in a 1:1 ratio. The primary end point was the therapeutic impact of 1-month metformin combination treatment on low-density lipoprotein cholesterol (LDL-C) and PCSK9 levels. Baseline LDL-C and PCSK9 levels were 76.18 mg·dL -1 and 80.54 ng·mL -1 , respectively. After 1 month, metformin significantly reduced LDL-C (-20.81%, P < 0.001), enabling 72% of patients to attain guideline-recommended LDL-C goals. Noteworthy reductions in PCSK9 levels (-15.03%, P < 0.001) were observed. Moreover, Met + CLA markedly reduced LDL particle number more than CLA alone (-10.65% vs. 1.45%, P = 0.009), primarily due to diminished small-dense LDL particle count. Mechanistically, our study demonstrated metformin's inhibition of statin-induced PCSK9 expression in human hepatocellular cells. In summary, a 1-month metformin combination regimen reduced LDL-C levels in patients with CAD but without diabetes by inhibiting PCSK9 expression. Chinese Clinical Trial Registry identifier: ChiCTR1900026925 (26/10/2019).

Effects of dietary intervention on diabetic nephropathy: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials.

To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN incidence. The literature was searched via PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as "high", "moderate", "low" or "very low" quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories. We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles. Moderate-quality evidence suggested that probiotic supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in DN patients. Low-quality evidence indicated that probiotic supplementation significantly improved the serum creatinine concentration, urinary albumin-creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low-quality evidence suggested that a salt restriction diet could significantly improve the creatinine clearance rate (CrCl) in patients with DN. Low-quality evidence suggested that vitamin D supplementation could significantly improve the UACR in patients with DN. In addition, low-quality evidence has indicated that soy isoflavone supplementation could significantly improve BUN, FBG, total cholesterol (TC), triglyceride (TG) and LDL-C levels in patients with DN. Furthermore, low-quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low-quality evidence suggested that supplementation with antioxidant vitamins could significantly improve the serum creatinine concentration, systolic blood pressure, and HbA1c level in patients with DN. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence. Moderate to low amounts of evidence suggest that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, or salt-restricted diets may significantly improve clinical outcomes in patients with DN. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024512670.

Biomarkers of lipid metabolism in gastric cancer: a case control study

BackgroundThe aim of this study was to explore the correlation between biomarkers of lipid metabolism and gastric cancer.Methods1120 gastric cancer patients and 1134 health examiners enrolled in this study. The clinic data and serum lipid level, including Total cholesterol (TC), Triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C) and High-density lipoprotein cholesterol (HDL-C), were collected.ResultsSerum TG and LDL-C levels in patients with gastric cancer were higher than those in the control group. HDL-C levels were lower than the control group (P < 0.05). HDL-C and LDL-C were significantly correlated with the risk of gastric cancer. Concentrating on clinicopathological features, increased TG was more frequently in male patients with distal gastric cancer, N0 stage and early TNM stage. Increased TC was more frequently in early T, N and TNM stage. Decreased HDL-C was more common in distal location and low-undifferentiated gastric cancer. LDL-C elevation was more common in distal gastric cancer and early T stage.ConclusionsThe serum lipid level of gastric cancer patients was higher than healthy controls. HDL-C and LDL-C abnormal correlated with gastric cancer risk. However, as the progresses of gastric cancer, poor patient intake, increased tumor consumption, and continuous declining in nutritional status, the levels of TC and TG gradually decreased in advanced gastric cancer.

Impact of 12-SNP and 6-SNP Polygenic Scores on Predisposition to High LDL-Cholesterol Levels in Patients with Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) comprises high LDL-cholesterol (LDL-c) levels and high cardiovascular disease risk. In the absence of pathogenic variants in causative genes, a polygenic basis was hypothesized. In a population of 418 patients (excluding homozygotes) with clinical suspicion of FH, the FH-causative genes and the regions of single nucleotide polymorphisms (SNPs) included in 12-SNP and 6-SNP scores were sequenced by next-generation sequencing, allowing for the detection of pathogenic variants (V+) in 220 patients. To make a comparison, only patients without uncertain significance variants (V-/USV-) were considered (n = 162). Higher values of both scores were observed in V+ than in V-. Considering a cut-off leading to 80% of V-/USV- as score-positive, a lower prevalence of patients positive for both 12-SNP and 6-SNP scores was observed in V+ (p = 0.010 and 0.033, respectively). Mainly for the 12-SNP score, among V+ patients, higher LDL-c levels were observed in score-positive (223 mg/dL -IQR 187-279) than in negative patients (212 mg/dL -IQR 162-240; p = 0.006). Multivariate analysis confirmed the association of scores and LDL-c levels independently of age, sex, and presence of pathogenic variants and revealed a greater association in children. The 12-SNP and 6-SNP polygenic scores could explain hypercholesterolemia in patients without pathogenic variants as well as the variability of LDL-c levels among patients with FH-causative variants.

Achievement of target LDL-cholesterol level in patients with acute coronary syndrome undergoing percutaneous coronary intervention: The JET-LDL registry

BackgroundIn patients with acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level < 1.4 mmol/L (<55 mg/dL). MethodsThe JET-LDL is a multicenter, observational, prospective registry created to investigate levels of LDL-C in consecutive patients with ACS undergoing PCI at 35 Italian hospitals, and to report their lipid lowering therapies (LLT). Follow-up was planned at 1 and 3 months. LDL-C reduction >50% from baseline or level < 55 mg/dL at 1-month was the primary endpoint. ResultsA total of 1095 patients were included: median age was 67 (58–75); 33.7% were already on LLT. Baseline LDL-C levels was 105 (76.5–137) mg/dL. At hospital discharge all patients were on LLT: 98.1% received statins (as mono or combination therapy), ezetimibe and PCSK9i were used in 60.1% and 8.5% of cases, respectively. Primary endpoint was achieved in 62% (95% CI 58–65) of cases. At 1-month LDL-C levels dropped to 53 (38–70) mg/dL (p < 0.001 vs baseline) and it was <55 mg/dL in 53% (95% CI 49–57) of patients; however, PCSK9i were added to 7 further cases. At 3-months 58% (95% CI 55–62) of patients achieved the target level, but PCSK9i was added to only 11 new patients. ConclusionsIn this real-world registry of ACS patients undergoing PCI, recommend LDL-C levels were obtained in 62% of patients, but PCSK9i prescription was limited to 10% of cases. As LLT pattern appeared mainly improved at hospital discharge, an early and strong treatment should be considered.

Dyslipidaemia in patients with chronic kidney disease - a neglected cardiovascular risk factor.

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). In addition, CKD itself is a coronary artery disease equivalent due to its atherogenic potential. Despite the role of CKD in ASCVD and recommendations to control lipid levels aggressively, landmark lipid studies have often excluded patients with advanced CKD. Furthermore, there is a scarcity of data on the use and efficacy of lipid-lowering therapy (LLT) in those with CKD in South Africa (SA). To determine the prevalence and control of dyslipidaemia in a cohort of SA patients with CKD. A retrospective, cross-sectional observational study of 250 patients with CKD attending the Charlotte Maxeke Johannesburg Academic Hospital renal clinic from 1 July 2019 to 31 July 2020 was carried out. Lipograms, the use of LLT and achievement of target lipid levels were examined. The median (interquartile range) age of this cohort was 58 (46 - 69) years; 50.4% were males and 64.4% black African. Dyslipidaemia was prevalent in 83.6% (n=209) of patients. A total of 169 (67.6%) patients were on LLT, and of these only 28 (16.6%) achieved the recommended low-density lipoprotein cholesterol (LDL-C) target. Of those not on LLT, 51 (63%) were eligible for LLT and almost all were classified as either very high risk (64.2%) or high risk (28.4%) for ASCVD. Of those on LLT, all were on statin therapy, of which simvastatin at a mean dose of 20 mg daily was the most commonly prescribed LLT. This cohort comprised a large proportion of patients classified as high or very high risk for ASCVD. Despite this, the use of LLT was inadequate, and <20% of patients were at target LDL-C levels. These data suggest a greater need for awareness of initiating LLT to achieve recommended target LDL-C levels in patients with CKD.

Target LDL cholesterol level in patients with acute coronary syndromes undergoing percutaneous coronary intervention: The JET-LDL registry

Target LDL cholesterol level in patients with acute coronary syndromes undergoing percutaneous coronary intervention: The JET-LDL registry

Estimation of Small Dense LDL-Cholesterol Levels in Patients with Acute Coronary Syndrome.

Small dense LDL-cholesterol is an established risk factor for atherosclerosis, but it is not routinely measured in clinical practice, and its measurement has not yet been reimbursed. The Sampson equation that uses triglyceride and LDL-cholesterol levels has very recently been proposed to estimate small dense LDL-cholesterol levels. We validated its accuracy in patients with acute coronary syndrome.Serum samples were obtained on admission from hospitalized patients with acute coronary syndrome before heparinization. Small dense LDL-cholesterol levels were measured directly and were also estimated from triglyceride and LDL-cholesterol levels using the Sampson equation. The correlation between the Sampson's equation and direct measurement was investigated.A total of 55 patients were enrolled. The median age was 75 (65, 84) years old, and 35 (64%) were men. There was a moderate correlation between the two methods (r = 0.76, P < 0.001). A lower level of small dense LDL-cholesterol was independently associated with a greater overestimation of the Sampson equation.The Sampson equation is useful for estimating small dense LDL-cholesterol levels in patients with acute coronary syndrome. However, the estimated value may be overestimated in patients with low lipid profiles.

J-shaped association between LDL cholesterol and cardiovascular events: A longitudinal primary prevention cohort of over 2.4 million people nationwide

IntroductionLow-density lipoprotein (LDL) cholesterol-lowering treatment is beneficial for the secondary or primary prevention of high-risk atherosclerotic cardiovascular disease (ASCVD). However, the prognostic implications of low LDL cholesterol levels in patients without previous ASCVD and without statin use remain elusive. MethodsFrom a nationwide cohort, 2,432,471 participants without previous ASCVD or statin use were included. For myocardial infarction (MI) and ischemic stroke (IS), participants were followed-up from 2009 to 2018. They were stratified according to 10-year ASCVD risk (<5 %, 5 %–<7.5 %, 7.5 %–<20 %, and ≥20 %) and LDL cholesterol level (<70, 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL). ResultsThe relationship between LDL cholesterol levels and ASCVD events exhibited a J-shaped curve for both MI and IS. After classification according to the ASCVD risk, this J-shaped relationship was consistently observed for the composite of MI and IS. Participants with an LDL cholesterol level <70 mg/dL showed a higher MI risk than those with a level of 70–99 mg/dL or 100–129 mg/dL in the low-ASCVD risk group. The J-shaped curve between LDL cholesterol levels and MI risk was attenuated across ASCVD risk groups. For IS, participants with an LDL cholesterol level <70 mg/dL demonstrated increased risks compared with those with a level of 70–99 mg/dL, 100–129 mg/dL, or 130–159 mg/dL in the borderline, intermediate, and high ASCVD risk groups, respectively. In contrast, a linear association was observed in participants taking statins. Interestingly, a J-shaped association was observed between LDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) levels; the mean hs-CRP level and the proportion of individuals with increased hs-CRP levels were relatively high among individuals with an LDL cholesterol level <70 mg/dL. ConclusionsAlthough high LDL cholesterol levels increase the risk of ASCVD, low LDL cholesterol levels do not warrant safety from ASCVD. Therefore, individuals with low LDL cholesterol levels should be carefully monitored.

Efficacy of Mobile-Based Cognitive Behavioral Therapy on Lowering Low-density Lipoprotein Cholesterol Levels in Patients With Atherosclerotic Cardiovascular Disease: Multicenter, Prospective Randomized Controlled Trial.

Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). However, low adherence to medication and lifestyle management has limited the benefits of lowering lipid levels. Cognitive behavioral therapy (CBT) has been proposed as a promising solution. This trial aimed to evaluate the efficacy of mobile-based CBT interventions in lowering LDL-C levels in patients with ASCVD. This multicenter, prospective, randomized controlled trial enrolled 300 patients with ASCVD, who were randomly assigned to the mobile-based CBT intervention group and the control group in a ratio of 1:1. The intervention group received CBT for ASCVD lifestyle interventions delivered by WeChat MiniApp: "CBT ASCVD." The control group only received routine health education during each follow-up. The linear regression and logistic regression analyses were used to determine the effects of a mobile-based CBT intervention on LDL-C, triglyceride, C-reactive protein, the score of General Self-Efficacy Scale (GSE), quality of life index (QL-index), and LDL-C up-to-standard rate (<1.8 mmol/L) at the first, third, and sixth months. Finally, 296 participants completed the 6-month follow-up (CBT group: n=148; control group: n=148). At baseline, the mean LDL-C level was 2.48 (SD 0.90) mmol/L, and the LDL-C up-to-standard rate (<1.8 mmol/L) was 21.3%. Mobile-based CBT intervention significantly increased the reduction of LDL-C change (%) at the 6-month follow-up (β=-10.026, 95% CI -18.111 to -1.940). In addition, this benefit remained when baseline LDL-C <1.8 mmol/L (β=-24.103, 95% CI -43.110 to -5.095). Logistic regression analysis showed that mobile-based CBT intervention moderately increased the LDL-C up-to-standard rates (<1.8 mmol/L) in the sixth month (odds ratio 1.579, 95% CI 0.994-2.508). For GSE and QL-index, mobile-based CBT intervention significantly increased the change of scores (%) at the 1-, 3-, and 6-month follow-up (all P values <.05). In patients with ASCVD, mobile-based CBT is effective in reducing LDL-C levels (even for those who already had a standard LDL-C) and can improve self-efficacy and quality of life. Chinese Clinical Trial Registry ChiCTR2100046775; https://www.chictr.org.cn/showproj.aspx?proj=127140.

Relationship between Changes in Blood Glucose and Blood Lipid Levels and the Risk of Thyroid Cancer in Patients with Type 2 Diabetes Mellitus.

To investigate the relationship between changes in blood glucose and blood lipid levels and the risk of thyroid cancer in patients with type 2 diabetes mellitus. A total of 159 patients with type 2 diabetes who were treated in our hospital between June 2018 and February 2021 were recruited and assigned into the observation group, including 136 patients with type 2 diabetes without thyroid cancer (nonthyroid cancer group) and 23 patients with type 2 diabetes complicated with thyroid cancer (thyroid cancer group), and 120 healthy subjects during the same period were selected as the control group. Glycated hemoglobin (HbAlc), total cholesterol (TC), triacylglycerol (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were detected and compared. Pearson's method was conducted to analyze the correlation between serum HbAlc level and TC, TG, HDL-C, and LDL-C levels in patients with type 2 diabetes mellitus; multivariate logistic regression analysis was performed to analyze the influencing factors of thyroid cancer in patients with type 2 diabetes mellitus. The serum HbAlc level and the incidence of thyroid cancer in patients with type 2 diabetes mellitus in the observation group were significantly higher than those in the control group (P < 0.05). The levels of TC, TG, and LDL-C in patients with type 2 diabetes mellitus in the observation group were significantly higher than those in the control group, and the level of HDL-C was significantly lower than that in the control group (P < 0.05). The correlation analysis showed that serum HbAlc levels in patients with type 2 diabetes were positively correlated with TC and TG levels and negatively correlated with HDL-C levels (P < 0.05) and not correlated with LDL-C levels (P > 0.05). Compared with the type 2 diabetes patients without thyroid cancer, the serum HbAlc, TC, and TG levels of the patients with type 2 diabetes mellitus in the thyroid cancer group were significantly higher, and the levels of HDL-C were significantly lower (P < 0.05). There was no significant change in the level of LDL-C (P > 0.05). Multivariate logistic regression analysis showed that serum HbAlc, TC, and TC levels were all risk factors for thyroid cancer in patients with type 2 diabetes mellitus (P < 0.05), while serum HDL-C level was a protective factor for thyroid cancer in patients with type 2 diabetes mellitus (P < 0.05). Thyroid cancer in type 2 diabetes patients may be linked to elevated levels of blood HbAlc, TC, and TG. HbAlc may raise the risk of thyroid cancer in type 2 diabetes patients by modulating blood lipid levels, which might serve as a marker to assess the risk of thyroid cancer in type 2 diabetes mellitus patients. However, since this study did not conduct in vitro and in vivo experiments, how HbAlc affects the pathogenesis of thyroid cancer has not been described in this study, which is also our future research direction. It is expected to provide new ideas for the prevention and treatment of thyroid cancer.

French expert group proposal for lipid-lowering therapy in the first 3 months after acute myocardial infarction.

In patients admitted for acute myocardial infarction (MI), it has been demonstrated that reducing LDL cholesterol (LDL-c) is associated with a reduction in major adverse cardiovascular events. We describe a consensual proposal made by a French group of experts for lipid-lowering therapy at the acute phase of acute myocardial infarction. A group of French experts comprising cardiologists, lipidologists and general practitioners prepared a proposal for a lipid-lowering strategy with a view to optimizing LDL-c levels in patients hospitalized for myocardial infarction. We describe a strategy for the use of statins, ezetimibe and and/or proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, with a view to reaching target LDL-c levels as early as possible. This approach, which is currently feasible in France, could considerably improve lipid management in patients after ACS, thanks to its simplicity, rapidity and the magnitude of the decrease in LDL-c that it achieves.

Inclisiran: A Review in Hypercholesterolemia.

Inclisiran (Leqvio®) is a first-in-class, subcutaneously administered, small interfering RNA (siRNA) that prevents hepatic synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9), thereby decreasing circulating low-density lipoprotein cholesterol (LDL-C). In the EU, inclisiran is indicated in adults with primary hypercholesterolemia or mixed dyslipidemia, as an adjunct to diet. It is intended for use in patients unable to reach LDL-C goals on maximally tolerated statin therapy, with or without other lipid-lowering therapies (LLTs). In patients who are statin intolerant or for whom a statin is contraindicated, it can be used with or without other LLTs. In clinical trials, twice-yearly injections of inclisiran (after initial doses at days 1 and 90) approximately halved LDL-C levels in patients with, or at high risk of developing, atherosclerotic cardiovascular disease (ASCVD) who had hypercholesterolemia, irrespective of whether or not their existing treatment included a statin. The safety and tolerability profile of the drug was similar to placebo, although mild to moderate, transient injection-site adverse reactions were more frequent with inclisiran. Pending confirmation of the expected reduction in cardiovascular (CV) events with inclisiran, it is a valuable additional/alternative antihyperlipidemic agent to a statin, as its infrequent maintenance dosing regimen confers a convenience advantage over other non-statin LLTs.

Use of Lipoprotein(a) to improve diagnosis and management in clinical familial hypercholesterolemia

Background and aimsLipoprotein(a) (Lp(a)) is an LDL-like particle whose plasma levels are largely genetically determined. The impact of measuring Lp(a) in patients with clinical familial hypercholesterolemia (FH) referred for genetic testing is largely unknown. We set out to evaluate the contribution of (genetically estimated) Lp(a) in a large nation-wide referral population of clinical FH. MethodsIn 1504 patients referred for FH genotyping, we used an LPA genetic instrument (rs10455872 and rs3798220) as a proxy for plasma Lp(a) levels. The genetic Lp(a) proxy was used to correct LDL-cholesterol and reclassify patients with clinical FH based on Dutch Lipid Criteria Network (DLCN) scoring. Finally, we used estimated Lp(a) levels to reclassify ASCVD risk using the SCORE and SMART risk scores. ResultsLPA SNPs were more prevalent among mutation-negative compared with mutation-positive patients (296/1280 (23.1%) vs 35/224 (15.6%), p = 0.016). Among patients with genetically defined high Lp(a) levels, 9% were reclassified to the DLCN category ‘unlikely FH’ using Lp(a)-corrected LDL-cholesterol (LDL-Ccor) and all but one of these patients indeed carried no FH variant. Furthermore, elevated Lp(a) reclassified predicted ASCVD risk into a higher category in up to 18% of patients. ConclusionsIn patients referred for FH molecular testing, we show that taking into account (genetically estimated) Lp(a) levels not only results in reclassification of probability of genetic FH, but also has an impact on individual cardiovascular risk evaluation. However, to avoid missing the diagnosis of an FH variant, clear thresholds for the use of Lp(a)-cholesterol adjusted LDL-cholesterol levels in patients referred for genetic testing of FH must be established.

A Systematic Review on the Safety and Efficacy of PCSK9 Inhibitors in Lowering Cardiovascular Risks in Patients With Chronic Kidney Disease.

Cardiovascular events caused by dyslipidemia are one of the leading causes of death in patients with Chronic Kidney Disease (CKD). Statins are the first line of treatment for patients with hyperlipidemia and in the treatment regimen for patients with CKD. Therefore, the introduction of Proprotein Convertase Subtilisin-Kexin type 9 inhibitors (PCSK9 inhibitors) is a viable and possibly effective treatment option for patients who, despite high doses of statins, struggle to lower their low-density lipoprotein cholesterol (LDL-C) levels. Our paper's objective is to explore the safety of these biological agents, particularly in patients with varying stages of impaired kidney function, and the correlating effectiveness in lowering their LDL-C levels, thereby reducing cardiovascular risks in these patients.We methodically retrieved relevant articles from PubMed, PubMed Central, Medline, and Google scholar in April 2022. We used the Medical Subject Heading (MeSH) Strategy and used the relevant keyword, then applied our inclusion and exclusion criteria; the initial search gave 10,542 results; with the removal of duplicates, irrelevant articles, and application of quality assessments done, we finally included 15 papers for our review with 37,188 patients.PCSK9 inhibitors are reliable, safe, and efficient therapy in lowering LDL-C levels in patients with CKD. However, its safety and efficacy in severe and end-stage kidney disease are grey, as other factors such as infections lead to morbidity and mortality. Future trials on chronic kidney disease and PCSK9 inhibitors should investigate the inhibitors' ability to improve kidney functions at all stages of kidney disease while lowering lipid levels and finally analyze the safety in patients with end-stage kidney disease.

New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins.

Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

Enigma of the cholesterol paradox in acute myocardial infarction: lessons from an 8-year follow-up of all-cause mortality in an age-matched and sex-matched case–control study with controls from the patients’ recruitment area

ObjectiveTo assess the impact of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) on long-term all-cause mortality (ACM) in patients with acute myocardial infarction (AMI) and controls.DesignMatched case–control study with...

A Case Series Assessing the Effects of Lomitapide on Carotid Intima-Media Thickness in Adult Patients with Homozygous Familial Hypercholesterolaemia in a Real-World Setting.

IntroductionHomozygous familial hypercholesterolaemia (HoFH) is characterised by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and results from multiple mutations in genes affecting the LDL receptor pathway. Patients are at risk of premature atherosclerotic cardiovascular disease (ASCVD) and premature death. Lomitapide is a microsomal triglyceride transfer protein inhibitor developed to treat HoFH, but cardiovascular outcome data are lacking.MethodsWe evaluated detailed data from five HoFH patients and one patient with heterozygous FH (HeFH) and a very severe phenotype. We also analysed confirmatory data from a further 8 HoFH cases. In total, we analysed data from patients in seven global centres in six countries who were all treated with lomitapide with long-term follow-up. Carotid intima-media thickness (CIMT) imaging was recorded on an ad hoc basis to monitor ASCVD in HoFH.ResultsLomitapide resulted in marked decreases in LDL-C of 56.8–93.9% [77.7–93.9% in the 6 initial cases (mean nadir 64.8 ± 30.1 mg/dL); 56.8–86.0% in the 8 confirmatory cases (mean nadir 131.4 ± 38.2 mg/dL)]. CIMT regressed in 50% of cases (mean follow-up 5.0 ± 3.1 years in initial six cases, and 4.4 ± 1.4 years in confirmatory cases). In the remaining patients, CIMT showed little further change. In patients where assessments of plaque area were available, regression or stabilisation in CIMT was accompanied by clinically significant regression of plaque area.ConclusionsLomitapide reduces LDL-C levels in patients with HoFH and severe LDL-C phenotypes, and results in stabilisation and/or regression of CIMT, which is an established marker of ASCVD risk. Additional data are needed to determine if this confers a survival benefit in these very high-risk patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-02031-y.

RELATIONSHIP BETWEEN FASTING BLOOD GLUCOSE LEVELS AND LDL CHOLESTEROL LEVELS IN PATIENTS WITH TYPE-2 DIABETES MELLITUS IN DIPONEGORO NATIONAL HOSPITAL

Background: Diabetes Mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels above the normal range. Type-2 diabetes mellitus can cause lipid metabolism disorder. This study analyzed the relationship between fasting blood glucose and LDL cholesterol levels in type-2 diabetes mellitus patients.Aim: To prove the correlation between fasting blood glucose levels with LDL cholesterol levels in patients with type-2 diabetes mellitus.Methods: This research is an observational analytical study with cross-sectional design on 40 subjects. The secondary data for this research was obtained from diabetic patients at Diponegoro National Hospital. The correlation analysis was done using Spearman Rank test.Results: Spearman Rank analysis showed no significant association between fasting blood glucose levels with LDL cholesterol levels in patients with type-2 diabetes mellitus (p = 0,119 and r = 0,250).Conclusion: There was no significant correlation between fasting blood glucose levels with LDL cholesterol levels in patients with Type-2 Diabetes Mellitus.

Lomitapide Reduces LDL-C and Favourably Affects Carotid Intima Media Thickness in Adult Patients with Homozygous Familial Hypercholesterolaemia in a Real-World Setting

<h3>Lead Author's Financial Disclosures</h3> D.B. has received consulting fees from Amryt. <h3>Study Funding</h3> Amryt Pharma. <h3>Background/Synopsis</h3> Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic condition characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-C) secondary to bi-allelic pathogenic mutations affecting key proteins in the LDL receptor pathway. Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor that acts independently of the LDL receptor and is licenced for the treatment of adult patients with HoFH. To date, there are few prospective cardiovascular outcomes data for HoFH patients receiving lomitapide. <h3>Objective/Purpose</h3> To evaluate the effect of lomitapide use on carotid intima-media thickness (CIMT) in patients with HoFH. <h3>Methods</h3> Thirteen HoFH patients (mean+/-SD age 29.3+/-12.5 years) in seven global centers were treated in accordance with the lomitapide product label and local clinical practice. Patients underwent routine laboratory testing, including lipid and liver panels. CIMT imaging was recorded to monitor atherosclerotic cardiovascular disease (ASCVD) according to local protocols. <h3>Results</h3> Lomitapide resulted in marked decreases in LDL-C (mean+/-SD: 76.5+/-11.7%; range 56.8-93.9% at the lowest point). Notably, eight patients achieved LDL-C levels below the European Atherosclerosis Society target of <100mg/dL, and three patients achieved LDL-C <70mg/dL at least once. Over a mean follow-up of 3.9+/-2.3 years between measurements, CIMT regressed in 7 cases. The remaining patients demonstrated no progression (Supplementary Table). In two patients where assessments of plaque area were available, modest regression or stabilisation in CIMT (0.82mm to 0.65mm over 24 months [20.7% reduction]; 0.56mm to 0.57mm over 26 months [1.8% increase]) was accompanied by clinically significant regression of plaque area (147.1mm2 to 120.5mm2 [18.1% reduction]; 64.0 mm2to 42.1 mm2 [34.7% reduction]. Calculation of vascular age in n=9 patients indicated mean improvement of -18.8+/-32.6 years (range -60 to +30 years). Elevations in ALT/AST enzyme levels >3x upper limit of normal were evident in 6/13 patients. In all cases, these elevations either resolved without intervention or were managed with brief, transient reductions in lomitapide dose. <h3>Conclusions</h3> Lomitapide dramatically reduces LDL-C levels in patients with HoFH, and results in stabilisation and/or regression of CIMT, which is an established marker of ASCVD risk.