Lower LDL Cholesterol Research Articles

A new indication for bempedoic acid (Nexletol).

The oral adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid was approved by the FDA in 2020 for use alone (Nexletol – Esperion) and in a fixed-dose combination with the cholesterol absorption inhibitor ezetimibe (Nexlizet) as an adjunct to maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL-cholesterol (LDL-C) lowering.

HYPERTRIGLYCERIDEMIA IN PATIENTS WITH ACUTE AND CHRONIC CORONARY SYNDROME: PREVALENCE AND THEIR ASSOCIATION WITH EXTREME CARDIOVASCULAR RISK AND LEFT VENTRICULAR FUNCTION

Objective: Hypertriglyceridemia prevalence in Acute and Chronic Coronary Syndrome (ACS and CCS respectively) patients in the era of very low LDL target is still unknow. The objective of our study is to evaluate the prevalence of triglyceride levels above 150 or 200 mg/dL despite statin therapy and LDL cholesterol at targets in ACS and CCS subjects enrolled in a Cardiac Rehabiliatitation (CR) program Design and method: This cross-sectional observational study was conducted at the Niguarda Hospital (Milan, Italy). Patients undergoing CR after ACS/CCS from January 1, 2012, to March 28, 2023, were included. Data on demographic, clinical, laboratory, and instrumental variables were collected. Results: The study population consisted of 740 patients with a mean age of 64.3±10.7 years, predominantly male (81.7%). Triglyceride levels significantly decrease during the CR period (131.1±63.8 vs 116.9±75.9 mg/dL; p < 0.001) similarly to LDL cholesterol (107.9 ± 38.8 mg/dL vs 69.9 ± 25.9mg/dL, p<0.001). 50.8% of the subjects reach the LDL cholesterol target. The percentage of patients with triglycerides >150 mg/dL at CR ends was 17.8% (15.6% when considering only patients that reach the LDL target of 55 mg/dL) while it is only 6.8% for triglycerides >200 mg/dL (5.9% when considering only patients that reach LDL target). Patients with triglycerides >150 mg/dL had higher baseline BMI, LDL cholesterol and uric acid with lower ejection fraction at CR ends. Hypertriglyceridemia significantly correlates with extreme CV risk (R= 0.08, p= 0.025). At multivariate analysis, FE (dependent variable) was significantly associated with triglycerides (beta= - 0,145, p= 0,026) and systolic BP (beta= 0,137, p= 0,032). Conclusions: Despite high intensity statin therapy and lower LDL cholesterol targets, a substantial proportion of patients in cardiac rehabilitation still had elevated triglyceride levels. This study highlights the potential role of Icosapent Ethyl in managing hypertriglyceridemia in these patients.

Women and familial hypercholesterolemia

Cardiovascular diseases (CVD) are the leading cause of death worldwide. One of the risk factors of CVDs is dyslipidemia, defined as the imbalance of lipids in the blood. Early diagnosis and treatment of the disease is important. However, there appears to be a gender disparity, with women less likely to be diagnosed and start lipid-lowering therapy. In addition, it is difficult for them to continue treatment without interruptions, such as for reasons of childbearing, and as a result they do not achieve the target Low Density Lipoproteins (LDL) levels. Heterozygous Familial Hypercholesterolaemia (FH) is thought to occur in 1 in 500 people in most ethnicities in the world. However, in most cases, these figures are derived from limited numbers of data from selected populations or specific subgroups in the general population and therefore may lack the precision of more modern estimates. About 1 in 200 people have familial hypercholesterolemia, but the vast majority are undiagnosed. Women with untreated FH are at very high risk for early-onset atherosclerotic cardiovascular disease. In untreated women with FH, 30% will develop Atherosclerotic Cardiovascular Disease (ASCVD) by age 60. The onset of ASCVD occurs 20 years earlier in life for women with FH than for women without FH. Regarding women with FH during menopause, they had similar LDL values to premenopausal women and higher levels compared to men in the same age group. Postmenopausal women with FH may suffer the consequences of high LDL either from delayed diagnosis or because of interruptions in management they may have experienced during childbearing. The last 2 decades have seen the development of new therapies to lower LDL-cholesterol levels and delay premature atherosclerosis, especially in combination with lifestyle modifications. Management of patients with familial hypercholesterolemia requires a multiprofessional approach, including primary care providers, cardiologists, endocrinologists, dietitians, pharmacists, and nurses, to improve outcomes. Treatment strategies should be discussed extensively at diagnosis. Close follow-up to monitor treatment response and development of side effects from lipid-lowering agents is essential to optimize care. The representation of women in studies concerning the diagnosis and treatment of familial hypercholesterolemia must be improved, so that there is a more effective treatment of this disease.

Inflammatory Bowel Disease exercise and diet (IBDeat) habits study: exploring lifestyle habits and cardiometabolic disease risk factors

Patients with inflammatory bowel disease (IBD) have higher risk of developing cardiometabolic diseases due to chronic gut and systemic inflammation which promotes atherogenesis. Adopting healthy lifestyle habits can prevent development of cardiometabolic diseases, but can be challenging for people with IBD. The IBD exercise and diet (IBDeat) habits study describes the lifestyle habits and cardiometabolic disease risk factors of adults with IBD in Aotearoa, New Zealand (NZ).This is a cross-sectional study including adult NZ IBD patients recruited online via Crohn’s and Colitis NZ and Dunedin hospital from 2021 to 2022. An online questionnaire collected demographics, smoking status, comorbidities, medications, disease severity scores, quality of life, physical activity, and dietary intake. The Dunedin cohort had physical measurements taken including anthropometrics, handgrip strength, blood pressure, body composition (bioelectrical impedance), blood nutritional markers, and faecal calprotectin. Data were compared to established reference values and linear regression analysis investigated associations between lifestyle habits and cardiometabolic risk factors. The study received University of Otago ethical approval (reference: H21/135). A total of 213 adults with IBD (54% Crohn’s disease; 46% ulcerative colitis) completed the online questionnaire and a subset of 102 from Dunedin provided physical measurements. Participants characteristics were: median age 37 (IQR 25, 51) years, 71% female, 82% NZ European, 4% smokers, and 1.4% had active IBD. Thirty-five percent of participants had at least one comorbidity and 34% of participants had poor quality of life. Known dietary risk factors associated with cardiometabolic diseases were common: low intakes of vegetables (77%), fruit (51%), fibre (35%) and high intakes of total fat (84%) and saturated fat (98%). Physical activity recommendations were met by 61% of participants and 63% reported barriers to being more active from fatigue (63%) and joint pain (54%). Other cardiometabolic risk factors were common in the Dunedin cohort: high LDL (79%) and total cholesterol (76%), central adiposity (64%), high body fat percentage (44%), high blood pressure (26%), and low handgrip strength (25%). Regression analysis showed that vegetable (per serve) and carbohydrate (per 5% of total daily energy intake (TE)) were associated with 0.22 mmol/L (95%CI 0.43, 0.013) and 0.20 mmol/L (95%CI 0.34, 0.057) lower LDL cholesterol. Discretionary food items were associated with higher LDL cholesterol, 0.11 mmol/L per daily serve (95%CI 0.028, 0.19). A 5% difference in TE intake from carbohydrate was associated with 1.11% (95%CI 2.22%, 0.0038%) lower body fat percentage while protein was associated with 3.1% (95%CI 0.81%, 5.39%) higher body fat percentage. Physical activity had weak associations with cardiometabolic disease risk factors. Adults with IBD have multiple modifiable risk factors for cardiometabolic diseases. Vegetable and carbohydrate intake were associated with lower LDL cholesterol concentration while discretionary food items showed otherwise. Protein intake was associated with higher body fat percentage.

There are those who would like zero LDL cholesterol.

The overwhelming evidence that the reduction of LDL cholesterol (LDLc) levels is associated with a parallel reduction in cardiovascular (CV) risk has led the scientific community to progressively and constantly reduce the optimal therapeutic targets of LDLc, both in patients with known CV disease and in patients undergoing primary prevention. The recent introduction of proprotein convertase subtilisin/kexin type 9 inhibitors has allowed clinicians to observe reductions in LDLc levels that go well beyond the limits set by the main international guidelines; following the 'the lower the better' paradigm, it is natural to ask how low LDLc can be reduced, whether this intervention is associated with a further reduction in CV risk and, above all, whether there are no issues related to safety in the use of polypharmacotherapies that determine an extreme reduction in LDLc levels. The purpose of this article is to summarize the main scientific evidence on the topic, trying to provide an answer to all clinicians who 'would like their LDLc to be-almost-zero'.

Eliminate LDL cholesterol after heart attack … but only for a while.

There is a clear demonstration of the inverse linear correlation between LDL cholesterol levels and clinical benefit. However, the timing of the action of lipid-lowering drugs is not clear. According to animal studies with recombinant lipoprotein A-1, the composition of atherosclerosis changes within 40 h (with variations in lipid and inflammatory contents). Progression-regression studies of atherosclerosis in humans confirm the data, highlighting a rapid change in the plaque over 5 weeks. The data are also in line with what emerges from the survival curves of the old study comparing atorvastatin 80 mg vs. placebo (Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering). The spacing of the curves occurs after only 4 weeks, indicating the precociousness of the favourable effects of powerful statins. Finally, a recent Odyssey post hoc analysis compared the risk of cardiac death and coronary revascularization between a group in which alirocumab lowered LDL cholesterol to below 15 mg (Group 1 and in which the drug was therefore stopped) against the subjects in the placebo group (Group 2), applying a propensity score matching. The primary endpoint occurred in a lower percentage of patients in Group 1 (6.4 vs. 8.4%). Furthermore, patients in Group 1 had a significantly lower hazard ratio (HR) for major adverse cardiovascular events [0.72; 95% confidence interval (CI) 0.51-0.997; P = 0.047] compared with the entire alirocumab group vs. placebo (HR 0.85; 95% CI 0.78-0.93; P < 0.001). According to these preliminary observations, aggressive and early treatment of hypercholesterolaemia in subjects with acute coronary syndrome translates into improved clinical results compared with a strategy that provides for more gradual control. These data will need to be confirmed through further prospective clinical studies and ideally with early conducted atherosclerosis regression studies.

Beyond cholesterol: Exploring serum ferritin’s and high-sensitivity C-reactive protein role in cardiovascular risk

Background: Iron, a pivotal element in the oxidation of low-density lipoprotein (LDL) cholesterol, exerts influence on inflammatory responses and exhibits a positive association with coronary heart disease. Elevated levels of the inflammatory marker, C-reactive protein (CRP), serve as a predictive risk factor for subsequent cardiac events. Aims and Objectives: This study explores the interplay between cardiovascular disease risk factors and serum ferritin concerning CRP. Materials and Methods: A cohort of 750 subjects (375 males and 375 females) was subjected to analysis. Elevated levels were defined as CRP &gt;3.0 mg/L, serum ferritin &gt;200 ng/mL, total cholesterol &gt;200 mg/dL, and LDL-cholesterol &gt;160 mg/dL. HDL cholesterol levels below 40 mg/dL were categorized as low. Results: Within the low LDL-cholesterol group, no discernible correlation was observed between serum ferritin and high-sensitivity CRP (hsCRP) (odds ratio [OR] of 54.95, 95% confidence interval [CI] = 0.81–3.48, P&lt;0.148). Conversely, a correlation was identified in the elevated LDL-cholesterol group (OR of 10.98, 95% CI=1.12–111.22, P&lt;0.05). Furthermore, the introduction of an interaction term in the assessment of the correlation between elevated hsCRP and LDL-cholesterol reaffirmed a robust correlation between hsCRP and serum ferritin (P&lt;0.005). Conclusion: The oxidation of LDL-cholesterol by serum ferritin emerges as a potential contributor to inflammatory reactions and heightened hsCRP levels. Prospective studies are warranted to investigate whether interventions targeting the reduction of serum ferritin and CRP levels, through medical interventions and lifestyle modifications, could prove efficacious in preventing cardiovascular diseases.

Overcoming therapeutic inertia in LDL cholesterol-lowering treatment with education and simplified treatment algorithms.

Overcoming therapeutic inertia in LDL cholesterol-lowering treatment with education and simplified treatment algorithms.

Eggs and a Fiber-Rich Diet Are Beneficially Associated with Lipid Levels in Framingham Offspring Study Adults

BackgroundFor many years, United States’ dietary policy recommended limiting egg intake to no more than 3/wk in the belief that restricting dietary cholesterol would lower plasma cholesterol levels and thereby reduce the risk of cardiovascular disease. The evidence supporting these recommendations is controversial. ObjectivesTo examine the impact of eggs, a major contributor to dietary cholesterol intake, on lipid levels and to determine whether these egg effects are modified by other healthy dietary factors in adults. MethodsMales and females aged 30–64 y with available 3-d diet record data, without cardiovascular disease and not taking lipid- or glucose-lowering medications in the prospective Framingham Offspring cohort were included (n = 1852). Analysis of covariance models were used to compare mean follow-up lipid levels adjusting for age, sex, BMI, and dietary factors. Cox proportional hazard’s models were used to estimate risk for elevated lipid levels. ResultsConsuming ≥5 eggs/wk was not adversely associated with lipid outcomes. Among men, consuming ≥5 (compared with <0.5) eggs/wk was associated with an 8.6 mg/dL lower total cholesterol level and a 5.9 mg/dL lower LDL cholesterol level, as well as lower triglycerides. Overall, higher egg intake combined with higher dietary fiber (compared with lower intakes of both) was associated with the lowest total cholesterol, LDL cholesterol, and LDL cholesterol–to–HDL cholesterol ratio. Finally, diets with higher (compared with lower) egg intakes in combination with higher total fish or fiber intakes, respectively, were associated with lower risks of developing elevated (>160 mg/dL) LDL cholesterol levels (hazard ratio: 0.61; 95% confidence interval: 0.44, 0.84; and HR: 0.70; 95% confidence interval: 0.49, 0.98, respectively). ConclusionsHigher egg intakes were beneficially associated with serum lipids among healthy adults, particularly those who consumed more fish and dietary fiber.

Diverse impacts of red palm olein, extra virgin coconut oil and extra virgin olive oil on cardiometabolic risk markers in individuals with central obesity: a randomised trial.

Dietary fats with an abundance of phytonutrients have garnered public attention beyond fatty acids per se. This study was set to investigate the impact of consuming diets with red palm olein (RPOO), extra virgin coconut oil (EVCO) and extra virgin olive oil (EVOO, as a control) on cardiometabolic risk biomarkers and lipid profile. We recruited a total of 156 individuals with central obesity, aged 25-45years, with waist circumference ≥ 90cm for men and ≥ 80cm for women in a parallel single-blind 3-arm randomised controlled trial. The participants consumed isocaloric diets (~ 2400kcal) enriched with respective test fats (RPOO, EVCO or EVOO) for a 12-week duration. The mean of the primary outcome plasma high sensitivity C-reactive protein was statistically similar between the three diets after a 12-week intervention. EVOO resulted in significantly lower mean LDL cholesterol compared with RPOO and EVCO, despite similar effects on LDL and HDL cholesterol subfractions. The RPOO diet group showed elevated mean and -carotenes levels compared with EVCO and EVOO diet groups (P < 0.05), corresponding with the rich carotenoid content in RPOO. The three oils, each of which has unique phytonutrient and fatty acid compositions, manifested statistically similar cardiometabolic effects in individuals with central obesity at risk of developing cardiovascular diseases with distinct circulating antioxidant properties. ClinicalTrials.gov (NCT05791370).

Fenugreek Leaves and Lemon are Mild to Moderately Effective Hypolipidemic Herbs to Lower Total Plasma Cholesterol, Triglycerides, and LDL Cholesterol in Primary and Secondary Hyperlipidemic Patients

In recent decades, some researchers assert that other newer lipid measurements, including non-HDL-C, apolipoprotein (apo) A-I, apoB, and lipid ratios, are superior to traditional LDL-C in predicting adverse outcomes in general population. Some researchers even suggest that apoB can replace the standard “lipid profile” as a target for motoring and therapy in at-risk patients. High plasma lipids interact with free radicals in human body leading to develop coronary artery disease. We in this study have compared hypolipidemic effects of Fenugreek, Curcuma longa, and Lemon. Study was conducted at Jinnah Hospital Lahore-Pakistan from January 2022 to May 2022. Ninety hyperlipidemic patients of age group 19 to 70 were included in the study. Exclusion criteria were diabetic, alcoholic additives, hypertensive patients and those whose kidney or liver functions were impaired. Consent was taken from all participants. Their base line lipid profile was taken in biochemistry laboratory of the hospital. They were divided in three groups i.e. 30 patients in each group. Group-I was advised to take 500 mg of Curcuma longa (haldi) mixed in fresh milk without cream, thrice daily for two months. Group-II patients were advised to take 100 grams of Fenugreek leaves mixed with salad in each meal (thrice daily) for the period of two months. Group-III patients were advised to take 40 ml of fresh lemon juice mixed with 40 ml mineral water thrice daily for two months. They all were advised not to take heavy meal rich with any type of fat like junk food etc. One hour daily brisk walk was advised to all participants. 15 days follow up visit was scheduled for them. After two months their lipid profile was re-determined. When results were compiled and statistically analyzed by applying paired ‘t’ test, it revealed that Curcuma longa decreased total cholesterol, TG, LDL cholesterol 16.10, 20.01, and 17.59 mg/dl respectively. Fenugreek decreased total cholesterol, TGs, and LDL cholesterol 14.70, 17.33, and 17.06 mg/dl respectively. Lemon in two months therapy decreased total cholesterol, TGs, and LDL cholesterol 15.45, 10.13, and 11.97 mg/dl respectively. None of the above mentioned herbs raised HDL cholesterol significantly. It was concluded from this research work that Curcuma longa, Fenugreek leaves and Lemon are mild to moderately effective hypolipidemic herbs to lower total plasma cholesterol, triglycerides, and LDL cholesterol but have no potential to raise HDL cholesterol when analyzed biostatistically.

A46 METABOLIC OUTCOMES 12-MONTHS POST-BARIATRIC SURGERY: SLEEVE VERSUS ROUX-EN-Y GASTRIC BYPASS

Abstract Background Obesity and its related comorbidities, such as type 2 diabetes (T2D), hyperlipidemia, cardiovascular disease (CVD), and non-alcoholic fatty liver disease (NAFLD) are on the rise. When lifestyle modifications, such as diet and exercise, are ineffective at producing sustained weight loss and improvements in obesity-related comorbidities, other interventions may be recommended. Bariatric surgery is considered in those who have a body mass index (BMI) over 40 kg/m2 or with comorbid conditions and a BMI between 35-40 kg/m2. Two commonly used procedures within this category of surgery are Roux-en-Y gastric bypass (RYGB), the gold standard for weight loss; and laparoscopic sleeve gastrectomy (LSG). Though both surgeries are effective at inducing weight loss, more information is needed on their comparative effectiveness in improving clinical and biochemical outcomes in patients with T2D, hyperlipidemia, and NAFLD in real-world practice. Aims Therefore, our objective was to determine the overall effectiveness of RYGB versus LSG at 12-months post-surgery and specifically assess their responses in those with hyperlipidemia, T2D and NAFLD. We chose to analyze both glucose and lipid parameters along with anthropometric measures as they not only provide insight into improvements in comorbid outcomes of obesity but also little-to-no prospective studies compare all of these outcomes in one study using the same cohort. Methods This is a prospective cross-sectional and cohort study of 142 patients who underwent bariatric surgery. Clinical and biochemical data were collected at baseline, prior to surgery and 12-months post-bariatric surgery. A liver biopsy was collected during surgery to diagnose NAFLD. The main outcome was 12-month changes in lipid parameters, mainly total cholesterol, between types of surgery. Results 107 individuals underwent RYGB (75.4%) and 35 underwent LSG (24.6%). Both groups were similar at baseline except for the higher waist circumference and proportion of males undergoing LSG. At 12-months post-surgery, RYGB versus LSG resulted in a significantly lower BMI (pampersand:003C0.0001), triglycerides (pampersand:003C0.05), total and LDL cholesterol (pampersand:003C0.005). Interestingly, ALT was significantly lower in those who underwent LSG (pampersand:003C0.005). In subgroup analysis for determining the effect of the type of surgery in those with comorbidities of obesity, RYGB was superior at improving lipid-related parameters in those with hyperlipidemia with a significant decrease in total cholesterol -0.48 (-0.84, 0.34) (pampersand:003C0.05) whereas LSG was superior at reducing ALT in those with NAFLD with significant decreases in total cholesterol and LDL. Conclusions RYGB leads to greater reductions in BMI and lipid parameters, especially in those with hyperlipidemia, whereas LSG showed greater improvements in liver enzymes in those with NAFLD. Funding Agencies CIHR

Dietary amino acid patterns and cardiometabolic risk factors among subjects with obesity; a cross-sectional study

BackgroundThe prevalence of obesity is a growing global public health concern. Certain dietary amino acids have been shown to have a potential therapeutic role in improving metabolic syndrome parameters and body composition in individuals with obesity. However, some amino acids have been linked to an increased risk of cardiometabolic disorders. This cross-sectional study aims to investigate the association between dietary amino acid patterns and cardiometabolic risk factors in individuals with obesity.MethodsThis cross-sectional study included 335 participants with obesity (57.9% males and 41.5% females) from Tabriz and Tehran, Iran. The participants were between the ages of 20–50, with a body mass index (BMI) of 30 kg/m2 or higher, and free from certain medical conditions. The study examined participants’ general characteristics, conducted anthropometric assessments, dietary assessments, and biochemical assessments. The study also used principal component analysis to identify amino acid intake patterns and determined the association between these patterns and cardiometabolic risk factors in individuals with obesity.ResultsUpon adjusting for potential confounders, the study found that individuals in the third tertiles of pattern 1 and 2 were more likely to have lower LDL levels (OR = 0.99 and 95% CI (0.98–0.99)) for both. Additionally, a significant decrease in total cholesterol was observed in the third tertiles of pattern 2 in model II (OR = 0.99, 95% CI (0.98–0.99)). These findings suggest a potential cardioprotective effect of these amino acid patterns in managing cardiometabolic risk factors in individuals with obesity.ConclusionsThis study found that two identified amino acid patterns were associated with lower serum LDL and total cholesterol levels, while a third pattern was associated with higher serum triglycerides. The specific amino acids contributing to these patterns highlight the importance of targeted dietary interventions in managing cardiometabolic risk factors in individuals with obesity.

Elevated remnant cholesterol and non-HDL cholesterol concentrations from real-world laboratory results: a cross-sectional study in Southeast Asians.

Triglyceride-rich remnant lipoproteins (TRLs) are considered atherogenic due to the presence of remnant cholesterol, which is transported by apolipoprotein B. In clinical practice, the concentration of TRLs can be estimated by calculating remnant cholesterol or non-HDL cholesterol levels. This study aims to investigate the proportion of patients who have low LDL cholesterol (LDL-C) concentration but elevated remnant cholesterol concentration, stratified by the presence of hypertriglyceridaemia and ethnicity, using real-world hospital data. Our secondary aim is to investigate the proportion of patients with elevated non-HDL cholesterol levels using guideline-recommended goals. A 2-year retrospective study was conducted at a single centre, analyzing lipid blood tests of all patients, including directly measured LDL-C. Fasting for blood tests was not mandatory. The study included a total of 21,605 consecutive patients with plasma lipid profiles analyzed in our hospital laboratory. The median age was 61 years. In patients with ASCVD (n = 14,704), 23.7% had an LDL-C level of <1.8 mmol/L, 11.3% had elevated remnant cholesterol concentrations at ≥0.65 mmol/L, and 48.8% were at the non-high-density lipoprotein cholesterol (non-HDL-C) goal (<2.6 mmol/L). Among patients diagnosed with atherosclerotic cardiovascular disease (ASCVD) with LDL-C levels of <1.8 mmol/L (n = 3,484), only 11.9% had high levels of remnant cholesterol, but 96% of the ASCVD patients also achieved the recommended non-HDL-C target of <2.6 mmol/L. When the LDL-C level was <1.8 mmol/L, the mean concentration of remnant cholesterol was 0.214 mmol/L when the triglyceride level was <1.7 mmol/L (n = 3,380), vs. 0.70 mmol/L when the triglyceride level was elevated (n = 724), p < 0.001. Among patients with a triglyceride level of ≥1.7 mmol/L and an LDL-C level of <.8 mmol/L, there were 254 patients with elevated remnant cholesterol concentration and 71 patients with suboptimal non-HDL levels. Malays had a higher mean remnant cholesterol concentration compared with both Chinese and Indians across all LDL-C levels, particularly in the presence of hypertriglyceridaemia. An elevated remnant cholesterol concentration of >0.65 mmol/L was present in 11% of all patients. The current guideline-recommended non-HDL-C goal, which uses a 0.8 mmol/L estimate of remnant cholesterol concentration, was achieved in >92% of patients, suggesting that it is unlikely to be clinically useful for the majority of our patient population except where there is concomitant hypertriglyceridaemia. Further studies are needed to establish the appropriate non-HDL-C goal or calculated remnant cholesterol concentration, paired with the LDL-C goal or otherwise, in a Southeast Asian population.

The impact of reproductive factors on the metabolic profile of females from menarche to menopause

We explore the relation between age at menarche, parity and age at natural menopause with 249 metabolic traits in over 65,000 UK Biobank women using multivariable regression, Mendelian randomization and negative control (parity only). Older age of menarche is related to a less atherogenic metabolic profile in multivariable regression and Mendelian randomization, which is largely attenuated when accounting for adult body mass index. In multivariable regression, higher parity relates to more particles and lipids in VLDL, which are not observed in male negative controls. In multivariable regression and Mendelian randomization, older age at natural menopause is related to lower concentrations of inflammation markers, but we observe inconsistent results for LDL-related traits due to chronological age-specific effects. For example, older age at menopause is related to lower LDL-cholesterol in younger women but slightly higher in older women. Our findings support a role of reproductive traits on later life metabolic profile and provide insights into identifying novel markers for the prevention of adverse cardiometabolic outcomes in women.

Perceived social support among percutaneous coronary intervention patients over a long-term follow-up period.

To investigate perceived social support and the associated factors as well as the sources of social support among post-percutaneous intervention patients over a long-term follow-up period. An explanatory and descriptive survey with a six-year follow-up (STROBE Statement: Supplementary file 1). Baseline data (n = 416) were collected from Finnish patients in 2013, with follow-up data collected from the same study group in 2019 (n = 154). The research employed the Social Support of Patients with Coronary Heart Disease self-reported questionnaire. Data were analysed using descriptive statistics and multivariate methods. In the acute phase, higher informational support was associated with lower LDL cholesterol and female gender and higher emotional support with working status. In long-term follow-up period, physical activity, younger age, normal cholesterol levels and previous percutaneous coronary intervention predicted higher informational support, regular participation in follow-up sessions and relationship status predicted higher emotional support, and previous coronary artery bypass grafting, smoking, alcohol consumption, normal cholesterol and regular follow-ups predicted higher functional support. No Patient or Public Contribution.

Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review

The potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in the management of COVID-19 and other medical conditions has emerged as an intriguing area of research. PCSK9 is primarily known for its impact on cholesterol metabolism, but recent studies have unveiled its involvement in various physiological processes, including inflammation, immune regulation, and thrombosis. In this abstract, the authors review the rationale and potential implications of PCSK9 inhibition during the inflammatory stage of SARS-CoV-2 infection. Severe cases of COVID-19 are characterized by an uncontrolled inflammatory response, often referred to as the cytokine storm, which can lead to widespread tissue damage and organ failure. Preclinical studies suggest that PCSK9 inhibition could dampen this inflammatory cascade by reducing the production of pro-inflammatory cytokines. Additionally, PCSK9 inhibition may protect against acute respiratory distress syndrome (ARDS) through its effects on lung injury and inflammation. COVID-19 has been linked to an increased risk of cardiovascular complications, especially in patients with pre-existing cardiovascular conditions or dyslipidemia. PCSK9 inhibitors are known for their ability to lower low-density lipoprotein (LDL) cholesterol levels by enhancing the recycling of LDL receptors in the liver. By reducing LDL cholesterol, PCSK9 inhibition might protect blood vessels from further damage and lower the risk of atherosclerotic plaque formation. Moreover, PCSK9 inhibitors have shown potential antithrombotic effects in preclinical studies, making them a potential avenue to mitigate the increased risk of coagulation disorders and thrombotic events observed in COVID-19. While the potential implications of PCSK9 inhibition are promising, safety considerations and possible risks need careful evaluation. Hypocholesterolemia, drug interactions, and long-term safety are some of the key concerns that should be addressed. Clinical trials are needed to establish the efficacy and safety of PCSK9 inhibitors in COVID-19 patients and to determine the optimal timing and dosing for treatment. Future research opportunities encompass investigating the immune response, evaluating long-term safety, exploring combination therapy possibilities, and advancing personalized medicine approaches. Collaborative efforts from researchers, clinicians, and policymakers are essential to fully harness the therapeutic potential of PCSK9 inhibition and translate these findings into meaningful clinical outcomes.

The role of structured inpatient lipid protocols in optimizing non-statin lipid lowering therapy: a review and single-center experience.

Dyslipidemia is a leading contributor to atherosclerotic cardiovascular disease (ASCVD). There has been a significant improvement in the treatment of dyslipidemia in the past 10 years with the development of new pharmacotherapies. The intent of this review is help enhance clinicians understanding of non-statin lipid lowering therapies in accordance with the 2022 American College of Cardiology Expert Consensus Clinical Decision Pathway on the Role of Non-statin Therapies for LDL-Cholesterol Lowering. We also present a single-center experience implementing a systematic inpatient protocol for lipid lowering therapy for secondary prevention of ASCVD.

Integrated compact regulators of protein activity enable control of signaling pathways and genome-editing in vivo

Viral proteases and clinically safe inhibitors were employed to build integrated compact regulators of protein activity (iCROP) for post-translational regulation of functional proteins by tunable proteolytic activity. In the absence of inhibitor, the co-localized/fused protease cleaves a target peptide sequence introduced in an exposed loop of the protein of interest, irreversibly fragmenting the protein structure and destroying its functionality. We selected three proteases and demonstrated the versatility of the iCROP framework by validating it to regulate the functional activity of ten different proteins. iCROP switches can be delivered either as mRNA or DNA, and provide rapid actuation kinetics with large induction ratios, while remaining strongly suppressed in the off state without inhibitor. iCROPs for effectors of the NF-κB and NFAT signaling pathways were assembled and confirmed to enable precise activation/inhibition of downstream events in response to protease inhibitors. In lipopolysaccharide-treated mice, iCROP-sr-IκBα suppressed cytokine release (“cytokine storm”) by rescuing the activity of IκBα, which suppresses NF-κB signaling. We also constructed compact inducible CRISPR-(d)Cas9 variants and showed that iCROP-Cas9-mediated knockout of the PCSK9 gene in the liver lowered blood LDL-cholesterol levels in mice. iCROP-based protein switches will facilitate protein-level regulation in basic research and translational applications.

Oreo Cookie Treatment Lowers LDL Cholesterol More Than High-Intensity Statin therapy in a Lean Mass Hyper-Responder on a Ketogenic Diet: A Curious Crossover Experiment.

Recent research has identified a unique population of 'Lean Mass Hyper-Responders' (LMHR) who exhibit increases in LDL cholesterol (LDL-C) in response to carbohydrate-restricted diets to levels ≥ 200 mg/dL, in association with HDL cholesterol ≥ 80 mg/dL and triglycerides ≤ 70 mg/dL. This triad of markers occurs primarily in lean metabolically healthy subjects, with the magnitude of increase in LDL-C inversely associated with body mass index. The lipid energy model has been proposed as one explanation for LMHR phenotype and posits that there is increased export and subsequent turnover of VLDL to LDL particles to meet systemic energy needs in the setting of hepatic glycogen depletion and low body fat. This single subject crossover experiment aimed to test the hypothesis that adding carbohydrates, in the form of Oreo cookies, to an LMHR subject on a ketogenic diet would reduce LDL-C levels by a similar, or greater, magnitude than high-intensity statin therapy. The study was designed as follows: after a 2-week run-in period on a standardized ketogenic diet, study arm 1 consisted of supplementation with 12 regular Oreo cookies, providing 100 g/d of additional carbohydrates for 16 days. Throughout this arm, ketosis was monitored and maintained at levels similar to the subject's standard ketogenic diet using supplemental exogenous d-β-hydroxybutyrate supplementation four times daily. Following the discontinuation of Oreo supplementation, the subject maintained a stable ketogenic diet for 3 months and documented a return to baseline weight and hypercholesterolemic status. During study arm 2, the subject received rosuvastatin 20 mg daily for 6 weeks. Lipid panels were drawn water-only fasted and weekly throughout the study. Baseline LDL-C was 384 mg/dL and reduced to 111 mg/dL (71% reduction) after Oreo supplementation. Following the washout period, LDL-C returned to 421 mg/dL, and was reduced to a nadir of 284 mg/dL with 20 mg rosuvastatin therapy (32.5% reduction). In conclusion, in this case study experiment, short-term Oreo supplementation lowered LDL-C more than 6 weeks of high-intensity statin therapy in an LMHR subject on a ketogenic diet. This dramatic metabolic demonstration, consistent with the lipid energy model, should provoke further research and not be seen as health advice.