Lipid Monitoring After Initiation of Lipid-Lowering Therapies: Return of Performance Measures?

PURPOSE OF REVIEW: The 2015 American College of Cardiology (ACC)/American Heart Association (AHA) Focused Update of Secondary Prevention Lipid Performance Measures removed low-density lipoprotein cholesterol (LDL-C) assessment as a performance measure. This review discusses the evidence supporting the importance of lipid monitoring in the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). RECENT FINDINGS: The 2018 AHA/ACC Multisociety cholesterol guideline (as did the 2013 guideline) recommends a lipid panel after initiating lipid-lowering therapy to monitor adherence and medication efficacy. The 2018 guideline also recommends adding nonstatin therapy in very-high-risk ASCVD patients with LDL-C ≥70 mg/dL despite maximally tolerated statin therapy. The removal of LDL-C monitoring as a performance measure is not consistent with the 2018 cholesterol guidelines. Given the importance of monitoring lipid-lowering medication efficacy and adherence and optimally reducing LDL-C in very-high-risk patients with additional evidence-based nonstatin therapy, LDL-C assessment after initiating lipid-lowering therapy should be reinstated as a performance measure for patients with ASCVD.

Goal achievement of HbA1c and LDL-cholesterol in a randomized trial comparing colesevelam with ezetimibe: GOAL-RCT.

AIM: To compare the efficacy and safety of colesevelam and ezetimibe as second-line low density lipoprotein-cholesterol (LDL-c)-lowering options in type 2 diabetes (T2D). MATERIALS AND METHODS: GOAL-RCT is a 24-week, open-label, randomized, pragmatic clinical trial. Subjects with T2D with uncontrolled HbA1c (7.1%-10%) and LDL-c (>2.0 mmol/L) were randomized 1:1 to colesevelam 3.75 g or ezetimibe 10 mg daily. The primary composite outcome was the proportion of participants achieving an LDL-c target of ≤2.0 mmol/L and HbA1c target of ≤7.0%. Intention to treat analysis was performed. RESULTS: Two hundred subjects were enrolled: mean age 59 ± 10 years; mean HbA1c 8.0%; mean LDL-c 2.5 mmol/L; 97% on statin therapy. The primary composite outcome was achieved by similar proportions of participants with colesevelam (14.6%) and ezetimibe (10.5%) (Pnon-inferiority < .001, Psuperiority = .41). LDL-c reduction from baseline was less with colesevelam compared with ezetimibe (14.0% vs. 23.2%, P < .01), as was the proportion of subjects achieving an LDL-c target of ≤2.0 mmol/L (47.6% and 67.0%, respectively; P = .007). Mean HbA1c was reduced with colesevelam (-0.26 ± 0.10%), while no change was observed with ezetimibe (difference P = .06). Adverse events and discontinuation rates were higher for colesevelam (20.2% and 31.1%) compared with ezetimibe (7.2% and 6.2%), respectively. CONCLUSIONS: Among subjects with T2D, the initiation of colesevelam or ezetimibe led to similar achievement of primary composite outcome (LDL-c and HbA1c within target), with ezetimibe recording a greater LDL-c reduction and better tolerability than colesevelam.

Comparing the serum TAG response to high-dose supplementation of either DHA or EPA among individuals with increased cardiovascular risk: the ComparED study.

Studies have shown that the reduction in serum TAG concentrations with long-chain n-3 fatty acid supplementation is highly variable among individuals. The objectives of the present study were to compare the proportions of individuals whose TAG concentrations lowered after high-dose DHA and EPA, and to identify the predictors of response to both modalities. In a double-blind, controlled, crossover study, 154 men and women were randomised to three supplemented phases of 10 weeks each: (1) 2·7 g/d of DHA, (2) 2·7 g/d of EPA and (3) 3 g/d of maize oil, separated by 9-week washouts. As secondary analyses, the mean intra-individual variation in TAG was calculated using the standard deviation from the mean of four off-treatment samples. The response remained within the intra-individual variation (±0·25 mmol/l) in 47 and 57 % of participants after DHA and EPA, respectively. Although there was a greater proportion of participants with a reduction >0·25 mmol/l after DHA than after EPA (45 υ. 32 %; P 0·25 mmol/l after both DHA and EPA had higher non-HDL-cholesterol, TAG and insulin concentrations compared with other responders at baseline (all P < 0·05). In conclusion, supplementation with 2·7 g/d DHA or EPA had no meaningful effect on TAG concentrations in a large proportion of individuals with normal mean TAG concentrations at baseline. Although DHA lowered TAG in a greater proportion of individuals compared with EPA, the magnitude of TAG lowering among them was similar.

Impact of meal fatty acid composition on postprandial lipaemia, vascular function and blood pressure in postmenopausal women.

CVD are the leading cause of death in women globally, with ageing associated with progressive endothelial dysfunction and increased CVD risk. Natural menopause is characterised by raised non-fasting TAG concentrations and impairment of vascular function compared with premenopausal women. However, the mechanisms underlying the increased CVD risk after women have transitioned through the menopause are unclear. Dietary fat is an important modifiable risk factor relating to both postprandial lipaemia and vascular reactivity. Meals rich in SFA and MUFA are often associated with greater postprandial TAG responses compared with those containing n-6 PUFA, but studies comparing their effects on vascular function during the postprandial phase are limited, particularly in postmenopausal women. The present review aimed to evaluate the acute effects of test meals rich in SFA, MUFA and n-6 PUFA on postprandial lipaemia, vascular reactivity and other CVD risk factors in postmenopausal women. The systematic search of the literature identified 778 publications. The impact of fat-rich meals on postprandial lipaemia was reported in seven relevant studies, of which meal fat composition was compared in one study described in three papers. An additional study determined the impact of a high-fat meal on vascular reactivity. Although moderately consistent evidence suggests detrimental effects of high-fat meals on postprandial lipaemia in postmenopausal (than premenopausal) women, there is insufficient evidence to establish the impact of meals of differing fat composition. Furthermore, there is no robust evidence to conclude the effect of meal fatty acids on vascular function or blood pressure. In conclusion, there is an urgent requirement for suitably powered robust randomised controlled trials to investigate the impact of meal fat composition on postprandial novel and established CVD risk markers in postmenopausal women, an understudied population at increased cardiometabolic risk.

Nutritional management of hyperapoB.

Plasma apoB is a more accurate marker of the risk of CVD and type 2 diabetes (T2D) than LDL-cholesterol; however, nutritional reviews targeting apoB are scarce. Here we reviewed eighty-seven nutritional studies and present conclusions in order of strength of evidence. Plasma apoB was reduced in all studies that induced weight loss of 6-12 % using hypoenergetic diets (seven studies; 5440-7110 kJ/d; 1300-1700 kcal/d; 34-50 % carbohydrates; 27-39 % fat; 18-24 % protein). When macronutrients were compared in isoenergetic diets (eleven studies including eight randomised controlled trials (RCT); n 1189), the diets that reduced plasma apoB were composed of 26-51 % carbohydrates, 26-46 % fat, 11-32 % protein, 10-27 % MUFA, 5-14 % PUFA and 7-13 % SFA. Replacement of carbohydrate by MUFA, not SFA, decreased plasma apoB. Moreover, dietary enriching with n-3 fatty acids (FA) (from fish: 1·1-1·7 g/d or supplementation: 3·2-3·4 g/d EPA/DHA or 4 g/d EPA), psyllium (about 8-20 g/d), phytosterols (about 2-4 g/d) or nuts (30-75 g/d) also decreased plasma apoB, mostly in hyperlipidaemic subjects. While high intake of trans-FA (4·3-9·1 %) increased plasma apoB, it is unlikely that these amounts represent usual consumption. Inconsistent data existed on the effect of soya proteins (25-30 g/d), while the positive association of alcohol consumption with low plasma apoB was reported in cross-sectional studies only. Five isoenergetic studies using Mediterranean diets (including two RCT; 823 subjects) reported a decrease of plasma apoB, while weaker evidence existed for Dietary Approaches to Stop Hypertension (DASH), vegetarian, Nordic and Palaeolithic diets. We recommend using a Mediterranean dietary pattern, which also encompasses the dietary components reported to reduce plasma apoB, to target hyperapoB and reduce the risks of CVD and T2D.

Cardiovascular risk assessment using SCORE2 in a population with hypertension - the reality at a primary health care unit.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Portugal, thus it is important to identify individuals at risk. Patients with hypertension have an increased risk of adverse cardiovascular (CV) events. The role of LDL cholesterol (LDL-C) in atherosclerotic CVD is well-established. SCORE2, a new CV risk calculation tool, is used to predict the 10-year risk of fatal or non-fatal CVD. The aim of this study was to understand the impact of SCORE2 on CV risk assessment in a population with hypertension from a moderate risk country, compared to the previously used SCORE. METHODS: This observational cross-sectional study analyzed a population census of 3146 patients diagnosed with hypertension without complications (K86). After applying inclusion and exclusion criteria, 654 patients were included. Data from medical records were collected to calculate and compare SCORE and SCORE2 categories and LDL-C targets. RESULTS: Patients were classified into SCORE categories: 188 (28.75%) low, 448 (68.5%) moderate, 17 (2.6%) high and 1 (0.15%) very high risk. Using SCORE2, individuals in the SCORE low risk category were reclassified, requiring new targets: 149 individuals (80%) as low to moderate and 39 (20%) as high risk. These differences became more evident when considering SCORE moderate and high-risk categories, where 358 patients (77%) received a higher CV risk categorization, and therefore a lower LDL-C target. There was a significant increase in individuals failing to meet the target when using SCORE2, compared to SCORE (p<0.001). CONCLUSION: These findings support the importance of CV risk assessment using SCORE2 algorithm in patients with hypertension.

A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis.

Background & Aims: Efruxifermin has shown clinical efficacy in patients with non-alcoholic steatohepatitis (NASH) and F1-F3 fibrosis. The primary objective of the BALANCED Cohort C was to assess the safety and tolerability of efruxifermin in patients with compensated NASH cirrhosis. Methods: Patients with NASH and stage 4 fibrosis (n = 30) were randomized 2:1 to receive efruxifermin 50 mg (n = 20) or placebo (n = 10) once-weekly for 16 weeks. The primary endpoint was safety and tolerability of efruxifermin. Secondary and exploratory endpoints included evaluation of non-invasive markers of liver injury and fibrosis, glucose and lipid metabolism, and changes in histology in a subset of patients who consented to end-of-study liver biopsy. Results: Efruxifermin was safe and well-tolerated; most adverse events (AEs) were grade 1 (n = 7, 23.3%) or grade 2 (n = 19, 63.3%). The most frequent AEs were gastrointestinal, including transient, mild to moderate diarrhea, and/or nausea. Significant improvements were noted in key markers of liver injury (alanine aminotransferase) and glucose and lipid metabolism. Sixteen-week treatment with efruxifermin was associated with significant reductions in non-invasive markers of fibrosis including Pro-C3 (least squares mean change from baseline [LSMCFB] -9 µg/L efruxifermin vs. -3.4 µg/L placebo; p = 0.0130) and ELF score (-0.4 efruxifermin vs. +0.4 placebo; p = 0.0036), with a trend towards reduced liver stiffness (LSMCFB -5.7 kPa efruxifermin vs. -1.1 kPa placebo; n.s.). Of 12 efruxifermin-treated patients with liver biopsy after 16 weeks, 4 (33%) achieved fibrosis improvement of at least one stage without worsening of NASH, while an additional 3 (25%) achieved resolution of NASH, compared to 0 of 5 placebo-treated patients. Conclusions: Efruxifermin appeared safe and well-tolerated with encouraging improvements in markers of liver injury, fibrosis, and glucose and lipid metabolism following 16 weeks of treatment, warranting confirmation in larger and longer term studies. Lay summary: Cirrhosis resulting from non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease, represents a major unmet medical need. Currently there are no approved drugs for the treatment of NASH. This proof-of-concept randomized, double-blind clinical trial demonstrated the potential therapeutic benefit of efruxifermin treatment compared to placebo in patients with cirrhosis due to NASH. Clinical Trial Number: NCT03976401.

Selective effect of laparoscopic Roux-en-Y gastric bypass on lipid metabolism. / Efecto selectivo de bypass gástrico laparoscópico en Y de Roux sobre el metabolismo lipídico.

INTRODUCTION: Bariatric surgery (BS) has shown to reduce cardiovascular morbidity and mortality in obesity. The BS has improved the dyslipidemia of the insulin resistant patient, our objective was to evaluate if there was a difference in the lipid profile between the laparoscopic roux-en-Y gastric bypass (RYGB) technique vs. the sleeve gastrectomy (SG) technique at 18 months of follow-up. METHODS: An observational, open, prospective study of morbidly obese patients who underwent bariatric surgery at 18-month follow-up. Anthropometric analysis, body composition, energy expenditure at rest, glucose, insulin, HbA1c, LDL, HDL, TG and CT were performed. RESULTS: Absence baseline differences were found in the proportion of patients with hypertension, diabetes, steatosis, and sex between the RYGB vs SG groups. A reduction of TG was observed at 6 months in favor of RYGB vs SG: 108.60±34.86 vs. 124.59±44.58, P = 0.044), however, a decrease in both LDL levels was found at 12 and 18 months in favor of the RYGB vs. SG group: 96.23±24.33 vs. 107.83±28.88, P = 0.025; 90.98±20.62 vs 106.22±31.48, P = 0.003; the decrease in CT was observed only at 18 months in favor of the RYGB vs. SG group: 171.39±25.058 vs. 186.89±31.81, P = 0.005. CONCLUSIóN: RYBG has shown to be more effective in reducing LDL and CT levels compared to SG, which provides an additional benefit of RYGB in relation to the lipid profile of the patient.

Lipid profile of patients treated with evolocumab in Spanish hospital nephrology units (RETOSS NEFRO).

BACKGROUND AND OBJECTIVE: To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain. MATERIAL AND METHODS: Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12±4 weeks post-initiation of evolocumab were reviewed. RESULTS: 60 patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular disease. The mean (SD) eGFR was 62.6 (30.0) ml/min/1.73m2 (51.7% of patients had eGFR <60ml/min/1.73m2 [CKD stage>2]), 50.0% had proteinuria (>300mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-c ≥160mg/dL and 29.3% ≥190mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100mg/dL, 70.0% <70mg/dL, and 55.0% <55mg/dL, while mean eGFR levels and statin use remained stable. CONCLUSION: In Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.

Rheumatoid Arthritis, Statin Indication and Lipid Goals: Analysis According to Different Recommendations.

BACKGROUND: Different strategies have been proposed for the cardiovascular risk management of patients with rheumatoid arthritis (RA). OBJECTIVES: (1) To estimate the cardiovascular risk by different strategies in RA patients, analyzing which proportion of patients would be candidates to receive statin therapy; (2) to identify how many patients meet the recommended lipid goals. METHODS: A cross-sectional study was performed from a secondary database. The QRISK-3 score, the Framingham score (adjusted for a multiplying factor×1.5), the ASCVD calculator and the SCORE calculator were estimated. The indications for statin therapy according to NICE, Argentine Consensus, ACC/AHA, and new European guidelines were analyzed. The recommended LDL-C goals were analyzed. RESULTS: A total of 420 patients were included. In total, 24.7% and 48.7% of patients in primary and secondary prevention were receiving statins, respectively. Only 19.4% of patients with cardiovascular history received high intensity statins. Applying the ACC/AHA guidelines (based on ASCVD score), the Argentine Consensuses (based on adjusted Framingham score), the NICE guidelines (based on QRISK-3) and European recommendations (based on SCORE), 26.9%, 26.5%, 41.1% and 18.2% of the population were eligible for statin therapy, respectively. Following the new European recommendations, 50.0%, 46.2% and 15.9% of the patients with low-moderate, high or very high risk achieved the suggested lipid goals. CONCLUSION: Applying four strategies for lipid management in our population, the cardiovascular risk stratification and the indication for statins were different. A significant gap was observed when comparing the expected and observed statin indication, with few patients achieving the LDL-C goals.

Pathogenic gain-of-function mutations in the prodomain and C-terminal domain of PCSK9 inhibit LDL binding.

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted protein that binds and mediates endo-lysosomal degradation of low-density lipoprotein receptor (LDLR), limiting plasma clearance of cholesterol-rich LDL particles in liver. Gain-of-function (GOF) point mutations in PCSK9 are associated with familial hypercholesterolemia (FH). Approximately 30%-40% of PCSK9 in normolipidemic human plasma is bound to LDL particles. We previously reported that an R496W GOF mutation in a region of PCSK9 known as cysteine-histidine-rich domain module 1 (CM1) prevents LDL binding in vitro [Sarkar et al., J. Biol. Chem. 295 (8), 2285-2298 (2020)]. Herein, we identify additional GOF mutations that inhibit LDL association, localized either within CM1 or a surface-exposed region in the PCSK9 prodomain. Notably, LDL binding was nearly abolished by a prodomain S127R GOF mutation, one of the first PCSK9 mutations identified in FH patients. PCSK9 containing alanine or proline substitutions at amino acid position 127 were also defective for LDL binding. LDL inhibited cell surface LDLR binding and degradation induced by exogenous PCSK9-D374Y but had no effect on an S127R-D374Y double mutant form of PCSK9. These studies reveal that multiple FH-associated GOF mutations in two distinct regions of PCSK9 inhibit LDL binding, and that the Ser-127 residue in PCSK9 plays a critical role.

Secular trends in serum lipid profiles in young adults in Norway, 2001-19.

Background: Lower prevalence of major cardiovascular disease (CVD) risk factors, such as dyslipidemia, hypertension and smoking, can explain a substantial part of the decline in CVD mortality and incidence for the past decades in Western countries. However, some studies have indicated less favorable trends in risk factors in recent years. We have assessed time trends in lipid profiles among young adults in Norway measured between 2001 and 2019. Methods: Samples of serum lipids analyzed at one large medical laboratory in Oslo, Norway, mainly requisitioned by primary care physicians, were analyzed cross-sectionally to estimate year-to-year trends among men and women aged 18-49 years. We also assessed the lipid distributions and proportions with adverse lipid levels. Results: In total, more than 2,6 million blood samples, comprising more than 1 million individuals (mean age 37.7 years) from all regions of Norway were included. All measures improved among all age groups in both women and men, especially in total and non-HDL cholesterol (-0.22 and -0.25 mmol/l per decade, respectively). There were downward shifts in the population distribution of total, non-HDL-C and LDL-C. The overall prevalences of total cholesterol ≥5.0 mmol/l and non-HDL-C ≥3.9 mmol/l similarly decreased, from ∼63 to 46% and from ∼52 to 34%, respectively. More than 1/3 had elevated levels of total and/or non-HDL-C in 2019. Conclusion: In a large proportion of the Norwegian population aged 18-49 years old, the lipid profiles improved during the last two decades. As the use of lipid-lowering medications is low in this age group, this likely reflects favorable secular trends.

The benefits of the Mediterranean diet in first episode psychosis patients taking antipsychotics.

Background: The side effects of antipsychotics (APs), related to weight gain and metabolic disturbances, can contribute to the health burden of psychotic people. Objective: To explore a) the level of adherence to the Mediterranean Diet (MedDiet) and consumption of fermented foods by first episode of psychosis (FEPs) patients taking APs, in comparison to matched -for age and BMI- healthy controls (HCs), and b) the effect of this dietary pattern on the biochemical and metabolic profile of FEPs. Method: The study population consisted of 33 FEPs treated with APs for less than 5 years, with no history of other chronic diseases, and an equal number of HCs. The FEPs were classified into two subgroups, according to their AP medication, depending on the documented risk of weight gain. A validated questionnaire for the adherence to Mediterranean diet and a food frequency questionnaire for selected fermented foods were completed by FEPs and HC. Anthropometric data and blood measurements were recorded for all participants. Results and conclusions: The FEPs showed a relevant lower overall adherence to the MedDiet, but no differences in consumption of fermented foods. Type of antipsychotic therapy uncovered differences in platelet count, vitamin B12, HDL and glucose (p < 0.05) between the subgroups of FEPs and HCs, although no values were abnormal. The MedDiet score was found to act as a prognostic factor for abnormal glucose levels in FEPs treated with APs associated with weight gain (p = 0.04). These results need to be confirmed by observations after long term adherence to MedDiet.

Temporal trends of lipid control in very high cardiovascular risk patients.

INTRODUCTION: Since 2011, the European guidelines have included a specific low-density lipoprotein cholesterol (LDL-C) target, <70 mg/dl, for very high cardiovascular risk (CVR) patients. However, registries have shown unsatisfactory results in obtaining this level of adequate lipid control. OBJECTIVES: To assess temporal trends in the use of lipid-lowering therapy (LLT) and attainment of adequate control in very high CVR patients since 2011. METHODS: We performed a retrospective observational study including very high CVR patients admitted in two periods: the first two years since the 2011 guidelines (2011/2012) and five years later (2016/2017). Lipid values, LLT, clinical variables and adequate lipid control rates were analyzed. RESULTS: A total of 1314 patients were reviewed (2011/2012: 638; 2016/2017: 676). Overall, 443 patients (33.7%) were not under LLT and only a slight improvement in drug prescription was observed from 2011/2012 to 2016/2017. In LLT users, the proportion of high-intensity LLT increased significantly in the later years (6.4% vs. 24.0%; p<0.001), but this was not associated with adequate lipid control. Overall, mean LDL-C was 95.4±37.2 mg/dl and adequate control was achieved in 320 patients (24.4%), without significant differences between 2011/2012 and 2016/2017 (p=0.282). Independent predictors of adequate control were male gender, older age, diabetes, chronic kidney disease, prior acute coronary syndrome, prior stroke and LLT, while stable coronary artery disease was associated with higher risk of failure. CONCLUSION: Even after the introduction of specific LDL-C targets, these are still not reached in most patients. Over a five-year period, LLT prescription only improved slightly, while adequate lipid control rates remained unchanged.

Lipid profile of patients treated with evolocumab in Spanish hospital nephrology units (RETOSS NEFRO). / Perfil clínico de los pacientes tratados con evolocumab en unidades hospitalarias de nefrología en España (RETOSS-NEFRO).

BACKGROUND AND OBJECTIVE: To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain. MATERIAL AND METHODS: Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12±4 weeks post-initiation of evolocumab were reviewed. RESULTS: Sixty patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular (CV) disease. The mean (SD) eGFR was 62.6 (30.0)ml/min/1.73m2 (51.7% of patients had eGFR<60ml/min/1.73m2 [CKD stage>2]), 50.0% had proteinuria (>300mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high-intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9)mg/dL (53.4% of patients with LDL-c≥160mg/dL and 29.3%≥190mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100mg/dL, 70.0% <70mg/dL, and 55.0% <55mg/dL, while mean eGFR levels and statin use were remained stable. CONCLUSION: In Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.

Pharmacodynamic study of the cardiovascular polypill. Is there any interaction among the monocomponents?

INTRODUCTION AND OBJECTIVES: To compare the pharmacodynamics of the CNIC polypill (atorvastatin 40mg/ramipril 10mg/aspirin 100mg) in terms of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP), with the corresponding reference products (atorvastatin and ramipril). METHODS: This was a multicenter, randomized, open-label, and parallel 3-arm study comparing the effect of the CNIC polypill vs ramipril 10mg and atorvastatin 40mg on SBP and LDL-C. The coprimary endpoints were differences in the adjusted mean 24-hour SBP (using ambulatory BP measurement) and LDL-C during the study period estimated using an ANCOVA model. RESULTS: Of the 241 patients included in the per protocol population, 84 received the CNIC polypill (group A), 84 atorvastatin (group B), and 73 ramipril (group C). SBP decreased from 139.3±12.5 to 133.2±12.9mmHg in group A and from 138.1±11.9 to 134.0±12.8mmHg in group C (baseline adjusted mean difference for the decrease in SBP was 1.77mmHg (90%CI, -0.5 to 4.0) in favor of group A, without reaching statistical significance. LDL-C was reduced by 33.9±21.6 and 29.2±25.8mg/dL in groups A and B, respectively (baseline adjusted mean difference for the decrease in LDL-C was 7.0% (90%CI, 1.5-12.4), a significantly greater decrease with the polypill). The 3 treatments were well tolerated. CONCLUSIONS: The results of this study rule out a negative effect on blood pressure of the interaction between the components of the CNIC polypill. The reduction in LDL-C was greater in the CNIC polypill group, suggesting a synergistic effect of the components.

Clinical laboratory characteristics of patients with obstructive jaundice accompanied by dyslipidemia.

BACKGROUND: Abnormal lipid metabolism manifests as hypercholesterolemia in patients with obstructive jaundice due to lipoprotein X (LpX). Our aim was to explore the clinical laboratory characteristics of patients with obstructive jaundice accompanied by dyslipidemia in a large number of samples. METHODS: A total of 665 patients with obstructive jaundice were included and categorized into two groups (with/without dyslipidemia) based on the ratio of the sum of HDL-c and LDL-c to total cholesterol [(HDL-c + LDL-c)/TC] with a cut-off value of 0.695. Laboratory liver, kidney, and blood lipid parameters were determined. Cholesterol composition assessment was performed by ultracentrifugation and high-performance liquid chromatography (UC-HPLC), and serum protein profiles were analyzed by capillary electrophoresis. RESULTS: Liver function in patients with obstructive jaundice accompanied by dyslipidemia was more aggravated than that in patients with simple obstructive jaundice (P < 0.05). The (HDL-c + LDL-c)/TC ratio was negatively correlated with bilirubin levels (P < 0.05). In addition, the difference in ApoB/LDL-c ratios was statistically significant between the obstructive jaundice accompanied by dyslipidemia group and healthy control group (P < 0.05). The LDL-c concentration determined by the UC-HPLC method was more than five times that determined by the enzymatic method (P < 0.05). Bisalbuminemia was found in 43 of 60 patients with obstructive jaundice accompanied by hypercholesterolemia. CONCLUSIONS: In patients with obstructive jaundice, the decreased (HDL-c + LDL-c)/TC ratio may be a novel marker to identify dyslipidemia secondary to LpX. The decreased ratio was associated with poor liver function and indicated disease progression.

Rheumatoid Arthritis, Statin Indication and Lipid Goals: Analysis According to Different Recommendations.

BACKGROUND: Different strategies have been proposed for the cardiovascular risk management of patients with rheumatoid arthritis (RA). OBJECTIVES: (1) To estimate the cardiovascular risk by different strategies in RA patients, analyzing which proportion of patients would be candidates to receive statin therapy; (2) to identify how many patients meet the recommended lipid goals. METHODS: A cross-sectional study was performed from a secondary database. The QRISK-3 score, the Framingham score (adjusted for a multiplying factor×1.5), the ASCVD calculator and the SCORE calculator were estimated. The indications for statin therapy according to NICE, Argentine Consensus, ACC/AHA, and new European guidelines were analyzed. The recommended LDL-C goals were analyzed. RESULTS: A total of 420 patients were included. In total, 24.7% and 48.7% of patients in primary and secondary prevention were receiving statins, respectively. Only 19.4% of patients with cardiovascular history received high intensity statins. Applying the ACC/AHA guidelines (based on ASCVD score), the Argentine Consensuses (based on adjusted Framingham score), the NICE guidelines (based on QRISK-3) and European recommendations (based on SCORE), 26.9%, 26.5%, 41.1% and 18.2% of the population were eligible for statin therapy, respectively. Following the new European recommendations, 50.0%, 46.2% and 15.9% of the patients with low-moderate, high or very high risk achieved the suggested lipid goals. CONCLUSION: Applying four strategies for lipid management in our population, the cardiovascular risk stratification and the indication for statins were different. A significant gap was observed when comparing the expected and observed statin indication, with few patients achieving the LDL-C goals.

Transient ischaemic attack after spacing the dose of alirocumab: Is it advisable to reduce the doses of PCSK9 inhibitors with very low LDL-cholesterols? / Accidente isquémico transitorio tras espaciar la dosis de alirocumab: ¿es recomendable reducir las dosis de iPCSK9 ante c-LDL muy bajos?

Inhibitors of the protein PCSK9, available since 2015, are capable of reducing the concentration of low density lipoprotein cholesterol by 40 to 70%, thus reducing the cardiovascular risk. The present case reports an adverse cardiovascular event that appeared when spacing out the administration of lipid-lowering treatment. A discussion will be presented on the importance of maintaining low cholesterol levels in order to achieve a greater benefit, according to the latest published clinical studies.

Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends.

BACKGROUND: Vanadium (V) is an element with a wide range of effects on the mammalian organism. The ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine. OBJECTIVE: This review aims at summarizing the current state of knowledge of the pharmacological potential of V and the mechanisms underlying its anti-viral, anti-bacterial, anti-parasitic, anti-fungal, anti-cancer, anti-diabetic, anti-hypercholesterolemic, cardioprotective, and neuroprotective activity as well as the mechanisms of appetite regulation related to the possibility of using this element in the treatment of obesity. The toxicological potential of V and the mechanisms of its toxic action, which have not been sufficiently recognized yet, as well as key information about the essentiality of this metal, its physiological role, and metabolism with certain aspects on the timeline is collected as well. The report also aims to review the use of V in the implantology and industrial sectors emphasizing the human health hazard as well as collect data on the directions of further research on V and its interactions with Mg along with their character. RESULTS AND CONCLUSIONS: Multidirectional studies on V have shown that further analyses are still required for this element to be used as a metallodrug in the fight against certain life-threatening diseases. Studies on interactions of V with Mg, which showed that both elements are able to modulate the response in an interactive manner are needed as well, as the results of such investigations may help not only in recognizing new markers of V toxicity and clarify the underlying interactive mechanism between them, thus improving the medical application of the metals against modern-age diseases, but also they may help in development of principles of effective protection of humans against environmental/occupational V exposure.