Lower Low-density Lipoprotein Cholesterol Research Articles

A Review of Low-Density Lipoprotein-Lowering Diets in the Age of Anti-Sense Technology.

This narrative review discusses an important issue, the primary role of diet in reducing low-density lipoprotein cholesterol (LDLc) concentrations in polygenic hypercholesterolemia. Two effective drugs, statins, and ezetimibe, that lower LDLc > 20% are relatively inexpensive and potential competitors to strict dieting. Biochemical and genomic studies have shown that proprotein convertase subtilisin kexin type 9 (PCSK9) plays an important role in low-density lipoprotein (LDL) and lipid metabolism. Clinical trials have demonstrated that inhibitory monoclonal antibodies of PCSK9 dose-dependently lower LDLc up to 60%, with evidence of both regression and stabilization of coronary atherosclerosis and a reduction in cardiovascular risk. Recent approaches using RNA interference to achieve PCSK9 inhibition are currently undergoing clinical evaluation. The latter presents an attractive option of twice-yearly injections. They are, however, currently expensive and unsuitable for moderate hypercholesterolemia, which is largely due to inappropriate patterns of eating. The best dietary approach, the substitution of saturated fatty acids by polyunsaturated fatty acids at 5% energy, yields > 10% lowering of LDLc. Foods such as nuts and brans, especially within a prudent, plant-based diet low in saturates complemented by supplements such as phytosterols, have the potential to reduce LDLc further. A combination of such foods has been shown to lower LDLc by 20%. A nutritional approach requires backing from industry to develop and market LDLc-lowering products before pharmacology replaces the diet option. Energetic support from health professionals is vital.

Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up

Background and aimsThe concentration and the duration of exposure to low-density lipoprotein cholesterol (LDL-C) (LDL-C burden) is an important determinant of risk for cardiovascular disease and thresholds has recently been estimated. Individuals with familial hypercholesterolemia (FH) have increased risk of premature cardiovascular disease. The overall aim of the present study was to describe differences in LDL-C level and LDL-C burden in females and males with FH visiting an outpatient lipid clinic from a young age, using multiple LDL-C measurements during a follow-up time of 12 years. First, we aimed to study if the LDL-C concentration and the LDL-C burden is different between females and males at ages 0–10, 10–20, 20–30 and >30 years. Second, we aimed to estimate the subject-specific LDL-C burden at age 19 and 30 years, and the proportion of female and male patients that reach suggested LDL-C thresholds indicating high risk of ASCVD. MethodsData was retrospectively collected from medical records of 438 subjects (207 girls and 231 boys) with FH, referred to the Lipid Clinic, Oslo University Hospital below the age of 19 years. The LDL-C burden was estimated based on repeated LDL-C measurements over time. ResultsSubjects were followed over a period of mean 12.0 (SD 7.0) years, with median 10 years (7–17; 25–75 percentiles, minimum 2), with median 6 (4–9; 25–75 percentiles, minimum 2) available LDL-C measurements, starting at mean age 11 (SD 3.9) years. There was a difference in both LDL-C and LDL-C burden between sexes at different ages. On average, males had lower LDL-C over time, although this difference was less pronounced with age and males also had lower estimated LDL-C burden over time, and this difference was further exacerbated with age. ConclusionOur study shows that young women with FH have a higher LDL-C burden than their male counterparts, potentially explaining the increased excess CVD risk seen among these. It underscores the importance of careful-follow up and early treatment initiation both prior to and after pregnancies in order to limit statin-free periods.

Network Meta-analysis of Chinese medicine injection combined with conventional western medicine in treatment of stable angina pectoris

This study aimed to systematically evaluate the efficacy and safety of different Chinese medicine injections combined with conventional western medicine for stable angina pectoris. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed were searched to collect randomized controlled trial(RCT) of Chinese medicine injection combined with conventio-nal western medicine in the treatment of stable angina pectoris from the inception of the databases to July 8, 2022. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. Stata 15.1 was used for network Meta-analysis. A total of 52 RCTs were included, involving 4 828 patients treated by 9 Chinese medicine injections(Danhong Injection, Salvia Miltiorrhiza Polyphenol Hydrochloride Injection, Tanshinone Sodium Ⅱ_A Sulfonate Injection, Salvia Miltiorrhiza Ligustrazine Injection, Dazhu Hongjingtian Injection, Puerarin Injection, Safflower Yellow Pigment Injection, Shenmai Injection and Xuesaitong Injection). The network Meta-analysis showed that:(1)in terms of improving the efficacy of angina pectoris, the surface under the cumulative ranking curve(SUCRA) followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Xuesaitong Injection>Shenmai Injection>Puerarin Injection>Safflower Yellow Pigment Injection>Dazhu Hongjingtian Injection;(2)in terms of improving the efficacy of electrocardiogram(ECG), SUCRA followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Puerarin Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Shenmai Injection>Xuesaitong Injection>Safflower Yellow Pigment Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(3)in terms of increasing high-density lipoprotein cholesterol(HDL-C), SUCRA followed the order of conventional western medicine combined with Danhong Injection>Shenmai Injection>Safflower Yellow Pigment Injection>Xuesaitong Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(4)in terms of lowering low-density lipoprotein cholesterol(LDL-C), SUCRA followed the order of conventional western medicine combined with Safflower Yellow Pigment Injection>Danhong Injection>Shenmai Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection>Xuesaitong Injection;(5)in terms of safety, the overall adverse reactions of Chinese medicine injection combined with conventional western medicine were less than those of the control group. Current evidence indicated that Chinese medicine injection combined with conventional western medicine could improve the curative effect of stable angina pectoris with higher safety. Limited by the number and quality of included studies, the above conclusion needed to be verified by more high-quality studies.

Silent Stroke -a Drag on Quality of Life

A stroke is a condition because of something blocking blood supply to part of the brain or when a blood vessel in the brain bursts disrupting the blood supply to a particular portion of the brain. In either case, parts of the brain become damaged or die, manifesting as lasting brain damage, long-term disability, or even death. Symptoms include dizziness, numbness, weakness on one side of the body, and problems with talking, writing, or understanding language. Most of us have heard or seen of a case of a stroke, with symptoms like slurred speech, loss of balance, difficulty speaking, and so on - but not many know that one can have a stroke without even knowing it? known as a silent stroke or Mini-stroke or asymptomatic cerebral infarction. A silent stroke refers to a stroke that doesn't cause any noticeable symptoms. It is recognized by a brain (CT scan or an MRI) imaging that will show white spots or lesions where your brain cells have stopped functioning. Brain scans can detect one or multiple silent strokes. Most silent strokes are caused by a clot that blocks a blood vessel in the brain. The blockage prevents blood and oxygen from reaching that area, causing nearby brain cells to die. While in the middle-aged people with no apparent signs of stroke about 10% have brain damage from one and this rate increases to 25% among people over 80 years. The damage that happens is permanent, but therapy might help stimulate other parts of the brain so you regain abilities that may have weakened. Common Silent Stroke Symptoms include sudden lack of balance, temporary loss of basic muscle movement slight memory loss and sudden changes in mood or personality and issues with cognitive skills and ability. As different parts of our brain control different parts of our body, our symptoms will depend on the part of our brain affected and the extent of the damage but usually begin suddenly. Therefore, it is critical to seek diagnosis and treatment as soon as possible. The chances of getting a stroke go up among elderly, diabetes, hypertensives, persons with heart disease, vascular disease, or atrial fibrillation. The management of silent strokes involves prescribing medications for blood thinning, to lower blood pressure, blood sugar, and serum cholesterol medications to lower low-density lipoprotein (LDL) cholesterol. The significant burden of stroke on the mortality rates in India, is well-documented, but robust data regarding the aggregates of evidence on the quality of life (QOL) of stroke survivors is limited. Therefore, it is critical to seek diagnosis and treatment as soon as possible. Material & Methods: This manuscript is based on a real case study in last 15 months. Chidambar a male of 70 years with history of Diabetes for over 15 years and Hypertension for 10 years, both poorly controlled. He had left sided hemiparesis following a stroke in January 2022, that resulted in left sided hemiparesis, speech, and cognitive signs. Since early 2023 he is suffering frequent falls, vomiting, urinary incontinence, changing moods and worsening memory and dementia indicative recurrent silent strokes, that have worsened his quality of life. Review of literature and published articles have added value to this article.

Current Insights on Dyslipidaemia Management for Prevention of Atherosclerotic Cardiovascular Disease: A Malaysian Perspective.

Dyslipidaemia is highly prevalent in the Malaysian population and is one of the main risk factors for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) is recognised as the primary target of lipid-lowering therapy to reduce the disease burden of ASCVD. Framingham General CV Risk Score has been validated in the Malaysian population for CV risk assessment. The Clinical Practice Guidelines (CPG) on the management of dyslipidaemia were last updated in 2017. Since its publication, several newer randomised clinical trials have been conducted with their results published in research articles and compared in meta-analysis. This underscores a need to update the previous guidelines to ensure good quality care and treatment for the patients. This review summarises the benefits of achieving LDL-C levels lower than the currently recommended target of < 1.8mmol/L without any safety concerns. In most high and very high-risk individuals, statins are the first line of therapy for dyslipidaemia management. However, certain high-risk individuals are not able to achieve the LDL-C goal as recommended in the guideline even with high-intensity statin therapy. In such individuals, lower LDL-C levels can be achieved by combining the statins with non-statin agents such as ezetimibe and PCSK9 inhibitors. Emerging non-statin lipid-lowering therapies and challenges in dyslipidaemia management are discussed in this article. The review also summarises the recent updates on local and international guidelines for dyslipidaemia management.

Preoperative serum low-density lipoprotein cholesterol is an independent prognostic factor in patients with renal cell carcinoma after nephrectomy

BackgroundLittle is known about the association between the preoperative low-density lipoprotein cholesterol (LDL-C) level and prognosis in patients with renal cell carcinoma (RCC) after nephrectomy, and its prognostic value needs to be elucidated.MethodsThe clinical and follow-up data of 737 RCC patients who underwent nephrectomy were retrospectively analyzed. The optimal cut-off LDL-C level was determined using X-tile, and then patients were divided into low and high LDL-C groups. The association between LDL-C levels and survival of RCC patients was assessed using the Kaplan-Meier method and Cox regression analysis.ResultsThe optimal cut-off LDL-C level was 1.93 mmol/L, and patients were divided into the low (≤ 1.93 mmol/L) and high LDL-C (> 1.93 mmol/L) groups. The Kaplan-Meier analysis showed that patients in the low LDL-C group had significantly shorter overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) than those in the high LDL-C group (P = 0.001, P = 0.001, and P = 0.003, respectively). The COX univariate analysis showed that the preoperative LDL-C level was closely associated with OS, CSS, and RFS in RCC patients (P = 0.002, P = 0.003, and P = 0.005, respectively). The multivariate analysis showed that the preoperative LDL-C level was an independent factor for predicting survival (OS, CSS and RFS) in RCC patients after nephrectomy. The low preoperative LDL-C levels predicted worse OS (hazard ratio [HR]: 2.337; 95% confidence interval [CI]: 1.192–4.581; P = 0.013), CSS (HR: 3.347; 95% CI: 1.515–7.392; P = 0.003), and RFS (HR: 2.207; 95% CI: 1.178–4.132; P = 0.013).ConclusionsThe preoperative LDL-C level is an independent factor for the prognosis of RCC patients after nephrectomy, and low preoperative LDL-C levels predict worse survival (OS, CSS, and RFS).

Efficacy and Safety of Evolocumab in Chinese Patients with Primary Hypercholesterolemia and Mixed Dyslipidemia: 12-Week Primary Results of the HUA TUO Randomized Clinical Trial.

Evolocumab, a fully human proprotein convertase/subtilisin kexin type9 inhibitor antibody, significantly lowers low-density lipoprotein cholesterol (LDL-C) in patients with type2 diabetes mellitus and hyperlipidemia and mixed dyslipidemia. This 12-week study evaluated the efficacy and safety of evolocumab in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia at different levels of cardiovascular disease risk. HUA TUO was a 12-week randomized, double-blind, placebo-controlled study. Chinese patients aged 18years or older on stable optimized statin therapy were randomized 2:2:1:1 to receive evolocumab 140mg every 2weeks (Q2W), evolocumab 420mg monthly (QM), or a matching placebo. The coprimary endpoints were percent change from baseline in LDL-C at the mean of weeks10 and 12 and at week12. Overall, 241 randomized patients (mean [standard deviation] age, 60.2 [10.3] years) received evolocumab 140mg Q2W (n = 79), evolocumab 420mg QM (n = 80), placebo Q2W (n = 41), or placebo QM (n = 41). At weeks10 and 12, the placebo-adjusted least-squares mean percent change from baseline in LDL-C for the evolocumab 140mg Q2W group was - 70.7% (95%CI - 78.0% to - 63.5%); - 69.7% (95%CI - 76.5% to - 63.0%) for the evolocumab 420mg QM group. Significant improvements in all other lipid parameters were observed with evolocumab. The patient incidence of treatment-emergent adverse events was similar between the treatment groups and across dosing regimens. In Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, 12-week treatment with evolocumab significantly lowered LDL-C and other lipids, and was safe and well tolerated (NCT03433755).

Higher Dietary Vitamin D Intake Influences the Lipid Profile and hs-CRP Concentrations: Cross-Sectional Assessment Based on The National Health and Nutrition Examination Survey.

Background. An unanswered question in the field of nutrition is whether there is an association between vitamin D intake and the lipid profile in adults. We conducted this cross-sectional study in order to investigate the impact of vitamin D intake on the lipid profile of adults in the context of the 2017-2018 National Health and Nutrition Examination Survey (NHANES). Methods. Serum lipids and high-sensitivity C-reactive protein (hs-CRP) concentrations and the Vitamin D intake in 2588 people aged 19 to 70 years was collected using laboratory analysis and 24-h recall, respectively. The one-way ANOVA test was used to compare quantitative variables and the chi-squared test was used to compare qualitative ones. Multivariate logistic regression for three models was performed to assess the odds ratio (OR) of high total cholesterol (TC) (>200 mg/dL), triglycerides (TG) (>150 mg/dL), low-density lipoprotein cholesterol (LDL-C) (>115 mg/dL), high-density lipoprotein cholesterol (HDL-C) (<40 mg/dL) and hs-CRP (>1 mg/l) based on the tertiles of dietary vitamin D (D2 + D3) intake. Results. After adjusting for age, sex, race, body mass index, serum 25-hydroxyvitamin D2, alcohol intake, energy intake, protein intake, carbohydrate intake, fiber intake and fat intake, individuals in the tertile with the highest versus lowest vitamin D intake (>1 mcg/day vs. <0.10 mcg/day) had lower odds of displaying elevated TC, LDL-C and hs-CRP concentrations (OR 0.57; CI: 0.37 to 0.88; P-trend: 0.045, OR 0.59; CI: 0.34 to 1.01; P-trend: 0.025 and OR 0.67; CI: 0.45 to 0.99; P-trend: 0.048, respectively). Based on the results of the logistic regression, no correlation between vitamin D intake and changes in TG or HDL-C values was noted. Conclusions. Our cross-sectional study indicates that higher dietary vitamin D (D2 + D3) intake is associated with lower TC, LDL-C and hs-CRP levels. No relationship between dietary vitamin D intake and TG or HDL-C values was detected. Further large-scale randomized trials are needed to evaluate the actual association between dietary vitamin D intake and the lipid profile.

Type 1 diabetes management: Room for improvement.

Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D). Ongoing improvement of management strategies requires the evaluation of target achievement and identification of risk factors in individuals who do (or do not) achieve these targets. Cross-sectional data were collected from adults with T1D visiting six diabetes centers in the Netherlands in 2018. Targets were defined as glycated hemoglobin (HbA1c) <53 mmol/mol, low-density lipoprotein-cholesterol (LDL-c) <2.6 mmoL/L (no cardiovascular disease [CVD] present) or <1.8 mmoL/L (CVD present), or blood pressure (BP) <140/90 mm Hg. Target achievement was compared for individuals with and without CVD. Data from 1737 individuals were included. Mean HbA1c was 63 mmol/mol (7.9%), LDL-c was 2.67 mmoL/L, and BP 131/76 mm Hg. In individuals with CVD, 24%, 33%, and 46% achieved HbA1c, LDL-c, and BP targets respectively. In individuals without CVD these percentages were 29%, 54%, and 77%, respectively. Individuals with CVD did not have any significant risk factors for HbA1c, LDL-c, and BP target achievement. In comparison, individuals without CVD were more likely to achieve glycemic targets if they were men and insulin pump users. Smoking, microvascular complications, and the prescription of lipid-lowering and antihypertensive medication were negatively associated with glycemic target achievement. No characteristics were associated with LDL-c target achievement. Microvascular complications and antihypertensive medication prescription were negatively associated with BP target attainment. Opportunities for improvement of diabetes management exist for the achievement of glycemic, lipid, and BP targets but may differ between individuals with and without CVD.

Addressing current challenges in optimization of lipid management following an ACS event: Outcomes of the ACS EuroPath III initiative.

Low-density lipoprotein cholesterol (LDL-C) lowering is key to reduce atherosclerotic disease progression and recurrent events for patients after acute coronary syndrome (ACS). However, LDL-C management for post-ACS patients remains challenging in clinical practice. The ACS EuroPath III project was designed to optimize LDL-C management in post-ACS patients by promoting guideline implementation and translating existing evidence into effective actions. Three surveys targeting cardiologists (n = 555), general practitioners (GPs; n = 445), and patients (n = 662) were conducted in Europe, with the aim of capturing information on patient characteristics and treatment during acute phase, discharge and follow-up. GPs' and patients' opinions on key treatment aspects were also collected. Based on survey results, international experts and clinicians identified areas of improvement and generated prototype solutions. Participants voted to select the most feasible and replicable proposals for co-development and implementation. Five key areas of improvement were identified: (1) inappropriate treatment prescribed at discharge; (2) lack of lipid guidance in the discharge letter; (3) inadequate lipid-lowering therapy (LLT) optimization; (4) gaps in guideline knowledge and lack of referral practices for GPs; (5) patients' concerns about lipid management. Proposed solutions for these focus areas included development of a treatment algorithm for the acute phase, a standardized GP discharge letter, an assessment tool for LLT efficacy at follow-up, an education plan for GPs/patients and a patient engagement discharge kit. The standardized GP discharge letter and treatment algorithm have been selected as the highest priority solutions for development. These initiatives have the potential to improve adherence to guidelines and patient management after ACS.

Association Between Achieved Low-Density Lipoprotein Cholesterol Levels and Long-Term Cardiovascular and Safety Outcomes: An Analysis of FOURIER-OLE.

Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for atherosclerotic cardiovascular disease. However, the optimal achieved LDL-C level with regard to efficacy and safety in the long term remains unknown. In FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), 27 564 patients with stable atherosclerotic cardiovascular disease were randomized to evolocumab versus placebo, with a median follow-up of 2.2 years. In the open-label extension (FOURIER-OLE), 6635 of these patients were transitioned to open-label evolocumab regardless of initial treatment allocation in the parent trial and were followed for an additional median of 5 years. In this prespecified analysis, we examined the relationship between achieved LDL-C levels (an average of the first 2 LDL-C levels measured) in FOURIER-OLE (available in 6559 patients) and the incidence of subsequent cardiovascular and safety outcomes. We also performed sensitivity analyses evaluating cardiovascular and safety outcomes in the entire FOURIER and FOURIER-OLE patient population. Multivariable modeling was used to adjust for baseline factors associated with achieved LDL-C levels. In FOURIER-OLE, 1604 (24%), 2627 (40%), 1031 (16%), 486 (7%), and 811 (12%) patients achieved LDL-C levels of <20, 20 to <40, 40 to <55, 55 to <70, and ≥70 mg/dL, respectively. There was a monotonic relationship between lower achieved LDL-C levels-down to very low levels <20 mg/dL-and a lower risk of the primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina or coronary revascularization) and the key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) that persisted after multivariable adjustment (adjusted Ptrend<0.0001 for each end points). No statistically significant associations existed in the primary analyses between lower achieved LDL-C levels and increased risk of the safety outcomes (serious adverse events, new or recurrent cancer, cataract-related adverse events, hemorrhagic stroke, new-onset diabetes, neurocognitive adverse events, muscle-related events, or noncardiovascular death). Similar findings were noted in the entire FOURIER and FOURIER-OLE cohort up to a maximum follow-up of 8.6 years. In patients with atherosclerotic cardiovascular disease, long-term achievement of lower LDL-C levels, down to <20 mg/dL (<0.5 mmol/L), was associated with a lower risk of cardiovascular outcomes with no significant safety concerns. URL: https://www. gov; Unique identifier: NCT01764633.

Benefit of Combination Ezetimibe/Simvastatin Among High-Risk Populations: Lessons from the IMPROVE-IT Trial.

The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) demonstrated the clinical benefit of the combination of ezetimibe-simvastatin compared to placebo-simvastatin following acute coronary syndrome (ACS). This review highlights key findings from this study with particular attention to the practice-changing impact on guidelines for low-density lipoprotein cholesterol (LDL-C) reduction after ACS, especially among high-risk populations. Consistent reductions in LDL-C have been reported with newer lipid-lowering therapies (proprotein convertase subtilisin/kexin type 9 inhibitors, cholesterol ester transfer proteins, bempedoic acid) in combination with statin in high-risk subgroups. Since high-risk subgroups remain a focus of guidelines, exploration of high-risk subgroups can help define the optimal use of new therapies. Ezetimibe reduced the LDL-C by 16.7mg/dL compared to placebo at 1year, resulting in a significant reduction in the primary composite endpoint (absolute risk difference 2.0%; relative risk difference 6.4%, hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). The benefits achieved with ezetimibein both LDL-C reduction and the primary clinical composite across 10 pre-specified high-risk subgroups, including the elderly; women; patients with diabetes, prior coronary artery bypass graft, history of stroke, polyvascular disease, low baseline LDL-C, renal dysfunction, prior heart failure, and an elevated TIMI risk score for secondary prevention, were similar or greater than in the corresponding non-high-risk subgroups. Safety events were similar between ezetimibe and placebo across the high-risk subgroups. These data support the addition of ezetimibe to statin therapy in high-risk patients who require additional therapy to lower the LDL-C post-ACS.

Prognostic value of low-density lipoprotein cholesterol in IgA nephropathy and establishment of nomogram model.

Dyslipidemia is closely related to kidney disease. We aimed to investigate the relationship between low-density lipoprotein cholesterol (LDL-C) and prognosis of IgA nephropathy (IgAN) and build a nomogram prognostic model. 519 IgAN patients with 61 months median follow-up were enrolled and divided into two groups based on the cut-off value of baseline LDL-C (2.60 mmol/L): the high group (n=253) and the low group (n=266). Renal survival was assessed by Kaplan⁃Meier (KM) survival curve. Risk factors were identified by COX regression analysis. The area under the receiver operating characteristic (ROC) curves (AUC), concordance index (C-index), and calibration curves were applied to evaluate the nomogram model. KM survival curve analysis showed that the high LDL-C group had worse renal survival than the low LDL-C group (χ2 = 8.555, p=0.003). After adjusting for confounding factors, Cox regression analysis showed the baseline LDL-C level was an independent risk factor of end-stage renal disease (ESRD) in IgAN (HR=3.135, 95% CI 1.240~7.926, p =0.016). LDL-C, segmental sclerosis, tubular atrophy/interstitial fibrosis, the prevalence of cardiovascular disease, 24-hour proteinuria were identified and entered into the nomogram models, with AUC of 0.864, 0.827, and 0.792 respectively to predict the 5-, 8-, and 10-year risk of ESRD in IgAN. The C-index of this prediction model was respectively 0.862, 0.838, and 0.800 and was well-calibrated. Elevated LDL-C level is a predictive factor for the prognosis of IgAN. We developed a nomogram model that can predict the risk of ESRD in IgAN by using LDL-C ≥ 2.60 mmol/L.

Underrepresentation of ethnic and regional minorities in lipid-lowering randomized clinical trials: a systematic review and meta-analysis.

The efficacy of lipid-lowering therapies (LLT) among different ethnicities and regions remains unclear. We aimed to assess cardiovascular event reductions associated with LLT according to ethnicity and region in previously published randomized clinical trials (RCTs). Medline, EMBASE and Cochrane CENTRAL were searched for RCTs of statins, ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors comparing intensive versus less intensive low-density lipoprotein cholesterol (LDL-C) lowering. The primary endpoint was major adverse cardiovascular events (MACE) defined as the composite of cardiovascular mortality, myocardial infarction, stroke and revascularisation. Random effects meta-analysis was used to pool risk ratios (RR) with 95% confidence intervals (CI) adjusted per mmol/L reduction in LDL-C. Fifty-three trials with 329,897 participants were included. Among participants, 39.5% were from Europe, 16.0% from North America, 9.0% from Japan, 2.8% from Australasia, 1.8% from South America, 1.1% from Asia, 0.6% from South Africa and 29.2% were unspecified. Among trials reporting ethnicities, there were 60.3% White, 20.2% Japanese, 9.4% Asian, 5.5% Black and 4.7% Latin American. There was reduction in MACE with LLT in regions including Australasia (RR 0.75, 95% CI 0.67-0.85), North America (RR 0.75, 95% CI 0.69-0.83), Europe (RR 0.78, 95% CI 0.71-0.86) and Japan (RR 0.73, 95% CI 0.63-0.85), and in Black ethnicity (RR 0.55, 95% CI 0.37-0.82). Head-to-head comparisons between regions and ethnicities revealed no significant differences in MACE reduction. Despite underrepresentation in clinical trials, regional and ethnic minority groups such as Australasia and Blacks appear to derive at least as much cardiovascular benefit from LLT.

Reduction of Cardiovascular Risk Using Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Acute Coronary Syndrome: A Systematic Review.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic enzyme that regulates blood cholesterol levels by degrading low-density lipoprotein (LDL) receptors from the surface of hepatocytes. Studies have shown that inhibiting this molecule decreases the cardiovascularrisk in individuals with atherosclerotic cardiovascular disease (ASCVD)by lowering low-density lipoprotein cholesterol (LDL-C). Two major cardiovascular outcome trials showed that the use of the PCSK9 inhibitors (alirocumab and evolocumab) in patients with recent acute coronary syndrome (ACS) is associated with a lower risk of further cardiovascular (CV) events. Information regarding the use of these monoclonal antibodies for primary prevention has also been reported by these trials. The goal of this systematic review is to describe the mechanism of PCSK9 inhibitors and further discuss their ability to reduce CV risk in high-risk populations. The search strategy was used in a systematic way using PubMed Central, Google Scholar, and ScienceDirect. We included randomized control trials (RCTs), systematic reviews, and narrative reviews in English published in the last five years. Observational studies,case reports, and case studies were excluded. The quality of the studies was evaluated using the Cochrane Collaboration Risk of Bias Tool, Assessment of Multiple Systematic Reviews 2, and Scale for the Assessment of Narrative Review Articles. A total of 10 articles were included in this systematic review. These included an RCT, a systematic review, and eight narrative reviews. Our study suggested that adding PCSK9 inhibitors to background statin therapy for selected patients with high-risk factors demonstrated substantial benefits in reducing overall CV morbidity and mortality after ACS. Multiple studies have demonstrated the short-term safety of low LDL-C levels caused by these drugs. However, long-term safety must be assessed with further studies.

Case report of familial hypobetalipoproteinemia: a novel APOB mutation and literature review.

Familial hypobetalipoproteinemia is an autosomal dominantly inherited disorder of lipid metabolism characterized by a <5th percentile plasma levels of low-density lipoprotein cholesterol or total apolipoprotein B, caused by mutations in the APOB gene. Patients with heterozygous APOB-related familial hypobetalipoproteinemia are usually asymptomatic or manifest with mild liver dysfunction or hepatic steatosis. A 14-year-old Korean boy was referred to our clinic because of low low-density lipoprotein cholesterol and elevated aminotransferase levels. He did not complain specific symptoms of hypobetalipoproteinemia, but his laboratory and radiologic tests showed low low-density lipoprotein cholesterol, low apolipoprotein B, high aminotransferases, severe fatty liver, and hepatosplenomegaly. A multigene panel test identified a heterozygous mutation for p.Lys3846Ter (c.11536A>T) in the APOB gene, which has not been reported in previous studies and was not detected in his parents with normal lipid profiles. Limiting intake of saturated fat, increased physical activity, and vitamin E supplementation were performed. Subsequent laboratory tests revealed normalized aminotransferase levels.

Association of Rare Protein-Truncating DNA Variants in APOB or PCSK9 With Low-density Lipoprotein Cholesterol Level and Risk of Coronary Heart Disease

Protein-truncating variants (PTVs) in apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with significantly lower low-density lipoprotein (LDL) cholesterol concentrations. The association of these PTVs with coronary heart disease (CHD) warrants further characterization in large, multiracial prospective cohort studies. To evaluate the association of PTVs in APOB and PCSK9 with LDL cholesterol concentrations and CHD risk. This studied included participants from 5 National Heart, Lung, and Blood Institute (NHLBI) studies and the UK Biobank. NHLBI study participants aged 5 to 84 years were recruited between 1971 and 2002 across the US and underwent whole-genome sequencing. UK Biobank participants aged 40 to 69 years were recruited between 2006 and 2010 in the UK and underwent whole-exome sequencing. Data were analyzed from June 2021 to October 2022. PTVs in APOB and PCSK9. Estimated untreated LDL cholesterol levels and CHD. Among 19 073 NHLBI participants (10 598 [55.6%] female; mean [SD] age, 52 [17] years), 139 (0.7%) carried an APOB or PCSK9 PTV, which was associated with 49 mg/dL (95% CI, 43-56) lower estimated untreated LDL cholesterol level. Over a median (IQR) follow-up of 21.5 (13.9-29.4) years, incident CHD was observed in 12 of 139 carriers (8.6%) vs 3029 of 18 934 noncarriers (16.0%), corresponding to an adjusted hazard ratio of 0.51 (95% CI, 0.28-0.89; P = .02). Among 190 464 UK Biobank participants (104 831 [55.0%] female; mean [SD] age, 57 [8] years), 662 (0.4%) carried a PTV, which was associated with 45 mg/dL (95% CI, 42-47) lower estimated untreated LDL cholesterol level. Estimated CHD risk by age 75 years was 3.7% (95% CI, 2.0-5.3) in carriers vs 7.0% (95% CI, 6.9-7.2) in noncarriers, corresponding to an adjusted hazard ratio of 0.51 (95% CI, 0.32-0.81; P = .004). Among 209 537 individuals in this study, 0.4% carried an APOB or PCSK9 PTV that was associated with less exposure to LDL cholesterol and a 49% lower risk of CHD.

Abstract TMP104: Effect Of Statin Therapy In Stroke Patients With Low Baseline Low-density Lipoprotein Cholesterol

Introduction: Post-stroke statin therapy is known to reduce subsequent major vascular events in patients with ischemic stroke. However, the efficacy of statin therapy in acute ischemic stroke patients with low low-density lipoprotein cholesterol (LDL-C) at baseline is not well defined. This study aimed to determine whether statin therapy would be beneficial in stroke patients with low or well-controlled LDL-C at baseline. Methods: We assessed ischemic stroke patients with baseline LDL-C &lt;100mg/dL without prior statin therapy or &lt;70mg/dL with prior statin therapy who were hospitalized between 2011 and 2020. The effect of post-stroke statin therapy on major vascular events, defined as a composite of recurrent stroke, myocardial infarction, and all-cause death within 1 year after stroke was assessed using multivariable Cox regression analyses. Results: A total of 3,350 patients (mean age 68.6 ± 13.9 years; 62.9% male; 21.5% with previous statin therapy; 37.0% with atherosclerotic stroke) were included. The mean baseline LDL-C of the patients was 73.6 ± 17.6mg/dL, which did not differ between patients with or without post-stroke statin therapy (74.0 ± 17.7mg/dL in statin users; 73.4 ± 17.6mg/dL in statin non-users). Statins were prescribed in 2,638 (78.8%) after stroke and LDL-C was significantly reduced in patients who received statin therapy (65.9 ± 21.7mg/dL in statin users; 80.2 ± 26.7mg/dL in statin non-users). Statin therapy was significantly associated with a lower risk of major vascular events (adjusted hazard ratios (aHR) 0.37 [95% confidence interval (CI) 0.31 - 0.46]). However, post-stroke LDL-C reduction (aHR 1.00 [95% CI 0.995 - 1.01]), percent LDL-C reduction (aHR 0.999 [95% CI 0.996 - 1.003]) and achieved LDL-C &lt;55mg/dL after stroke (aHR 0.96 [95% CI 0.67 - 1.37]) were not associated with the occurrence of major vascular events within 1 year after stroke. Conclusions: Post-stroke statin therapy was associated with a reduction in major vascular events after acute ischemic stroke, even in patients with low or well-controlled LDL-C. However, achieved LDL-C levels were not associated with post-stroke major vascular events in this population.

Evaluation of equations for calculating LDL-cholesterol in patients with concomitant hypertriglyceridemia and low LDL-cholesterol: is there a preferred equation?

It is critical to reliably estimate Low Density Lipoprotein Cholesterol (LDL-C) in patients with concomitant hypertriglyceridemia and low LDL-C. We retrospectively compared the performances of the Friedewald (LDL-F), Martin-Hopkins (LDL-MH) and Sampson (LDL-SA) equations against a direct homogeneous LDL-C assay (dLDL-C) on observations presenting mild hypertriglyceridemia (triglycerides between 1.69 and 3.9 mmol/L) and low LDL-C (< 2.58 mmol/L). Observations were stratified according to their LDL-C. Agreement of the equations with dLDL-C was assessed using Intraclass Correlation Coefficients (ICC) with an agreement cut-off of 0.9, and analysis of Bland-Altman plots. Independently of the LDL-C stratum evaluated, the three equations failed to meet the 0.9 ICC cut-off, although their agreement with dLDL-C improves as LDL-C increases. Analysis of Bland-Altman plots shows a downwards discordance of LDL-F with dLDL-C, and an upwards discordance of LDL-MH and LDL-SA with direct LDL-C. LDL-MH resulted in the least observations outside the Bland-Altman limits of agreement. While no equation can be deemed satisfactory enough to replace direct assays in patients with low LDL-C and concomitant hypertriglyceridemia, LDL-MH seems to perform better than the other equations in estimating LDL-C in these patients.

Elevated remnant cholesterol increase 6-year type 2 diabetes mellitus onset risk

AimTo investigate the association of remnant cholesterol (RC) with future type 2 diabetes mellitus (T2DM) risk, and to assess the underlying impact of some recognized risk factors on it. MethodsA total of 11468 nondiabetic adults in rural China were recruited in 2007–2008 and followed up in 2013–2014. Logistic regression was used to assess the risk of incident T2DM by quartiles of baseline RC, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Association of the combinations of RC and low-density lipoprotein cholesterol (LDL-C) with T2DM risk were further evaluated. ResultsMultivariable adjusted OR (95% CI) for incident T2DM associated with quartile 4 versus quartile 1 of RC was 2.72 (2.05–3.62). Per 1-standard deviation (SD) increases in RC levels was associated with a 34% higher T2DM risk. However, gender modified the specific association (Pinteraction < 0.05), with the association stronger among females. When combining the low LDL-C and low RC groups as reference, individuals with RC levels ≥ 0.56 mmol/L had more than a 2-fold T2DM risk, regardless of LDL-C level. ConclusionsElevated RC levels increase T2DM risk in rural Chinese populations. In those who cannot control their risk by lowering LDL-C levels, the goal of lipid-lowering therapy can be shifted to RC.