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Pros and cons for use of statins in people with coronavirus disease-19 (COVID-19).
Subir, R, Jagat J, M, Kalyan K, G
Diabetes & metabolic syndrome. 2020;(5):1225-1229
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Abstract
BACKGROUND AND AIMS Morbidity and mortality from coronavirus disease 2019 (COVID-19) is higher among people with diabetes mellitus (DM), hypertension, and cardiovascular disease (CVD). Statins are used in the majority of people with DM and CVD. This mini-review discusses the current understanding of benefit-risk ratio of use of statins in COVID-19. METHODS We searched PubMed database using specific keywords related to our aims till June 12, 2020. Full text of relevant articles published in English language were retrieved and reviewed. RESULTS Statins, with their immunomodulatory, anti-inflammatory, anti-thrombotic, and anti-oxidant properties, have the potential to reduce severity of lung injury in, and mortality from, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infections. Statin-induced upregulation of angiotensin-converting enzyme-2 (ACE2) has the potential to reduce lung injury from excess angiotensin II. By disrupting lipid rafts, statins have the potential to reduce viral entry into cells. However, benefit-risk ratio of its complex interaction with MYD88 gene expression on outcomes in COVID-19, and the putative role of low serum LDL cholesterol in increasing severity of SARS-CoV2 infection need further clarification. CONCLUSIONS People with COVID-19, who are already on statins for an underlying co-morbid condition, should continue on it unless there are specific contraindications. De-novo use of statins in people with COVID-19 with no underlying co-morbidity might be beneficial but awaits substantiation in clinical trials; till that time, de novo use of statins in COVID 19 should be limited to a clinical trial setting.
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The challenge of multiple cardiovascular risk factor control outside Western Europe: Findings from the International ChoLesterol management Practice Study.
Blom, DJ, Santos, RD, Daclin, V, Mercier, F, Ruiz, AJ, Danchin, N, ,
European journal of preventive cardiology. 2020;(13):1403-1411
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BACKGROUND Comprehensive control of multiple cardiovascular risk factors reduces cardiovascular risk but is difficult to achieve. DESIGN A multinational, cross-sectional, observational study. METHODS The International ChoLesterol management Practice Study (ICLPS) investigated achievement of European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline low-density lipoprotein cholesterol (LDL-C) targets in patients receiving lipid-modifying therapy in countries outside Western Europe. We examined the rate of, and association between, control of multiple risk factors in ICLPS participants with dyslipidaemia, diabetes and hypertension (N = 2377). RESULTS Mean (standard deviation) age of patients was 61.4 (10.4) years; 51.3% were male. Type 2 diabetes was the most common form of diabetes (prevalence, 96.9%). The prevalence of metabolic syndrome was 67.8%, obesity 40.4%, atherosclerotic disease 39.6% and coronary artery disease 33.5%. All patients were at high (38.2%) or very high (61.8%) cardiovascular risk according to ESC/EAS guidelines. Body mass index (BMI) was <25 kg/m2 in 20.3% of patients, 62.8% had never smoked and 25.2% were former smokers. Overall, 12.2% achieved simultaneous control of LDL-C, diabetes and blood pressure. Risk factor control was similar across all participating countries. The proportion of patients achieving individual guideline-specified treatment targets was 43.9% for LDL-C, 55.5% for blood pressure and 39.3% for diabetes. Multiple correspondence analysis indicated that control of LDL-C, control of blood pressure, control of diabetes, BMI and smoking were associated. CONCLUSION Comprehensive control of multiple cardiovascular risk factors in high-risk patients is suboptimal worldwide. Failure to control one risk factor is associated with poor control of other risk factors.
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Effectiveness of interventions for the reversal of a metabolic syndrome diagnosis: An update of a meta-analysis of mixed treatment comparison studies.
Guzmán, A, Navarro, E, Obando, L, Pacheco, J, Quirós, K, Vásquez, L, Castro, M, Ramírez, F
Biomedica : revista del Instituto Nacional de Salud. 2019;(4):647-662
Abstract
Introduction: Identifying the most effective interventions to reverse the metabolic syndrome can be key in the design of clinical strategies to prevent progression to type 2 diabetes mellitus and cardiovascular disease. Objective: To estimate the effect size of the interventions used for the reversal of metabolic syndrome. Materials and methods: We searched in Embase and Medline databases for randomized clinical trials with an outcome defined as the reversal of the metabolic syndrome diagnosis. We classified the interventions in four dimensions: 1) lifestyle (diet and exercise); 2) pharmaceuticals; 3) a combination of both, and 4) control groups, and we conducted a mixed treatment comparison analysis. Results: Additional to the previous meta-analysis published by Dunkley, et al. in 2012, we dentified two other studies. Lifestyle interventions had 2.61 more chances to achieve the reversal of the metabolic syndrome than the control group, with a credible interval between 1.00 and 5.47. Pharmaceutical treatments showed a 3.39 higher chance of reversing the syndrome compared with the control group, but the credible interval was estimated from 0.81 to 9.99. Lifestyle interventions had 1.59 more chance of reversal than the pharmaceutical treatments. Conclusion: Diet and physical activity-based interventions had a higher probability of effectiveness to reverse a metabolic syndrome diagnosis.
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Dyslipidaemia in nephrotic syndrome: mechanisms and treatment.
Agrawal, S, Zaritsky, JJ, Fornoni, A, Smoyer, WE
Nature reviews. Nephrology. 2018;(1):57-70
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Nephrotic syndrome is a highly prevalent disease that is associated with high morbidity despite notable advances in its treatment. Many of the complications of nephrotic syndrome, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidaemia. These abnormalities include elevated plasma levels of cholesterol, triglycerides and the apolipoprotein B-containing lipoproteins VLDL and IDL; decreased lipoprotein lipase activity in the endothelium, muscle and adipose tissues; decreased hepatic lipase activity; and increased levels of the enzyme PCSK9. In addition, there is an increase in the plasma levels of immature HDL particles and reduced cholesterol efflux. Studies from the past few years have markedly improved our understanding of the molecular pathogenesis of nephrotic syndrome-associated dyslipidaemia, and also heightened our awareness of the associated exacerbated risks of cardiovascular complications, progressive kidney disease and thromboembolism. Despite the absence of clear guidelines regarding treatment, various strategies are being increasingly utilized, including statins, bile acid sequestrants, fibrates, nicotinic acid and ezetimibe, as well as lipid apheresis, which seem to also induce partial or complete clinical remission of nephrotic syndrome in a substantial percentage of patients. Future potential treatments will likely also include inhibition of PCSK9 using recently-developed anti-PCSK9 monoclonal antibodies and small inhibitory RNAs, as well as targeting newly identified molecular regulators of lipid metabolism that are dysregulated in nephrotic syndrome.
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Genetic Variants Associated With Plasma Lipids Are Associated With the Lipid Response to Niacin.
Tuteja, S, Qu, L, Vujkovic, M, Dunbar, RL, Chen, J, DerOhannessian, S, Rader, DJ
Journal of the American Heart Association. 2018;(19):e03488
Abstract
Background Niacin is a broad-spectrum lipid-modulating drug, but its mechanism of action is unclear. Genome-wide association studies have identified multiple loci associated with blood lipid levels and lipoprotein (a). It is unknown whether these loci modulate response to niacin. Methods and Results Using data from the AIM - HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL /High Triglycerides and Impact on Global Health Outcomes) trial (n=2054 genotyped participants), we determined whether genetic variations at validated loci were associated with a differential change in plasma lipids and lipoprotein (a) 1 year after randomization to either statin+placebo or statin+niacin in a variant-treatment interaction model. Nominally significant interactions ( P<0.05) were found for genetic variants in MVK , LIPC , PABPC 4, AMPD 3 with change in high-density lipoprotein cholesterol; SPTLC 3 with change in low-density lipoprotein cholesterol; TOM 1 with change in total cholesterol; PDXDC 1 and CYP 26A1 with change in triglycerides; and none for lipoprotein (a). We also investigated whether these loci were associated with cardiovascular events. The risk of coronary disease related death was higher in the minor allele carriers at the LIPC locus in the placebo group (odds ratio 2.08, 95% confidence interval 1.11-3.90, P=0.02) but not observed in the niacin group (odds ratio 0.89, 95% confidence interval 0.48-1.65, P=0.7); P-interaction =0.02. There was a greater risk for acute coronary syndrome (odds ratio 1.85, 95% confidence interval 1.16-2.77, P=0.02) and revascularization events (odds ratio 1.64, 95% confidence interval 1.2-2.22, P=0.002) in major allele carriers at the CYP 26A1 locus in the placebo group not seen in the niacin group. Conclusions Genetic variation at loci previously associated with steady-state lipid levels displays evidence for lipid response to niacin treatment. Clinical Trials Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00120289.