Differential associations of statin treatment and polymorphism in genes coding for HMGCR and PCSK9 to risk for insomnia

Background: Atherosclerosis is a systemic, progressive lipid-driven inflammatory disease of the arterial vascular wall leading progressively to plaque development. The vulnerable plaque, the one considered to be the leading cause of cardiovascular events seems to exhibit a large and soft lipid-rich necrotic core covered by a thin and inflamed fibrous cap. Statin treatment is considered as one of the most effective methods for vulnerable plaque stabilization, currently being the principal drug in primary and secondary prevention of cardiovascular disease. Objective: We sought to evaluate the beneficial effect of statins on biological processes involved in the evolution of vulnerable plaques Method: We performed a systematic review of the literature searching MEDLINE via Pubmed for all experimental and human studies implementing statins in vulnerable plaque. Results: Statins seem to have a beneficial role in plaque stabilization and patient outcome. It seems that this effect is mediated by improving endothelial function, decreasing oxidative stress and inflammation, reducing inflammatory activation and inhibiting thrombogenic response. Although these data are quite promising, it remains to be determined the extent of a potent benefit of the pleiotropic effects of statin therapy in clinical setting. Conclusion: Prospective randomized trials should be conducted in order to further elucidate differences among type and dose of statin therapy, duration of treatment and association with LDL levels and clinical outcome.

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Diabetes-induced Alterations in HDL Subfractions Distribution

Current Pharmaceutical Design ◽

10.2174/1381612825666190227224246 ◽

2020 ◽

Vol 26 (27) ◽

pp. 3341-3348 ◽

Cited By ~ 1

Author(s):

Marek Femlak ◽

Anna Gluba-Brzozka ◽

Beata Franczyk ◽

Jacek Rysz

Keyword(s):

Diabetes Mellitus ◽

Cardiovascular Risk ◽

Public Health Problem ◽

Statin Treatment ◽

Oxidative Modification ◽

Control Group ◽

Newly Diagnosed ◽

Hdl Subfractions ◽

Patients With Diabetes ◽

Healthy Control

Introduction: Diabetes mellitus (DM) due to its increasing prevalence and associated morbidity and mortality has become a serious public health problem. In DM, HDL may lose its beneficial features and become proatherogenic due to its altered biological activity thus increasing cardiovascular risk. The aim of this study was to assess the influence of the presence of diabetes mellitus type 2 and its duration on the distribution of HDL subfractions. Moreover, the effect of statin treatment on HDL subfraction share was analysed in this study. Methods: The study group consisted of 50 patients with newly diagnosed DM and 50 persons with DM for longer than 10 years while the control group consisted of 50 healthy volunteers. HDL subfractions were analysed with the use of Lipoprint. Results: We demonstrated progressive worsening of heart functioning and impairment of its structure in the course of diabetes mellitus. Moreover, we observed that HDL-6 subfraction and intermediate HDL fraction are lowest in the group with advanced DMt2 compared to the group with newly diagnosed DM and a healthy control group. Finally, the results of our study indicated the effect of statin treatment on HDL subfractions that seems not to be advantageous. Conclusion: It seems that in patients with diabetes mellitus compromised antiatherogenic properties of HDL, as a result of oxidative modification and glycation of the HDL protein as well as the transformation of the HDL proteome into a proinflammatory protein, increase cardiovascular risk.

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Efficacy and Safety of Evolocumab in Reducing Low Density Lipoprotein Cholesterol Levels in Chinese Patients with Non-ST-segment Elevation Acute Coronary Syndrome

Current Vascular Pharmacology ◽

10.2174/1570161118666200616144141 ◽

2020 ◽

Vol 18 ◽

Author(s):

Xiaohan Xu ◽

Meng Chai ◽

Yujing Cheng ◽

Pingan Peng ◽

Xiaoli Liu ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Statin Treatment ◽

Chinese Patients ◽

Lipid Lowering ◽

Control Group ◽

Lipid Lowering Therapy ◽

St Segment Elevation ◽

Coronary Syndrome ◽

St Segment

Aims: To explore early intensive lipid-lowering therapy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels can reduce cardiovascular morbidity and mortality in patients with atherosclerotic cardiovascular disease. Due to many reasons, the need for early intensive lipid-lowering therapy is far from being met in Chinese NSTE-ACS patients at high-risk of recurrent ischaemic events. Objective: To evaluate the feasibility, safety and efficacy of starting evolocumab in hospital to lower LDL-C levels in Chinese patients with NSTE-ACS. Methods: In this prospective cohort study initiated by researchers, 334 consecutive patients with NSTE-ACS who had sub-standard LDL-C levels (LDL-C ≥2.3 mmol/L after regular oral statin treatment for at least 4 weeks; or LDL-C ≥3.2 mmol/L without regular oral statin treatment) were included. Patients who agreed to treatment with evolocumab (140 mg subcutaneously every 2 weeks, initiated in hospital and used for 12 weeks after discharge) were enrolled in the evolocumab group (n=96) and others in the control group (n=238). All enrolled patients received regular statin treatment (atorvastatin 20 mg/day or rosuvastatin 10 mg/day; doses unchanged throughout the study).The primary endpoint was the change in LDL-C levels from baseline to week 12. Results: Most patients (67.1%) had not received regular statin treatment before. In the evolocumab group, LDL-C levels decreased significantly at week 4 and remained stable at week 8 and 12 (all p<0.001). At week 12, the LDL-C percentage change from baseline in the evolocumab group was -79.2±12.7% (from an average of 3.7 to 0.7 mmol/L), while in the control group it was -37.4±15.4% (from an average of 3.3 to 2.0 mmol/L). The mean difference between these 2 groups was -41.8% (95% CI -45.0 to -38.5%; p<0.001). At week 12, the proportions of patients with LDL-C levels <1.8 mmol/L and 1.4 mmol/L in the evolocumab group were significantly higher than in the control group (96.8 vs 36.1%; 90.6 vs 7.1%; both p<0.001). The incidence of adverse events and cardiovascular events was similar in both groups. Conclusions: In this prospective cohort study we evaluated the early initiation of evolocumab in NSTE-ACS patients in China. Evolocumab combined with statins significantly lowered LDL-C levels and increased the probability of achieving recommended LDL-C levels, with satisfactory safety and well tolerance.

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Small dense LDL cholesterol is a robust therapeutic marker of statin treatment in patients with acute coronary syndrome and metabolic syndrome

Clinica Chimica Acta ◽

10.1016/j.cca.2011.04.021 ◽

2011 ◽

Vol 412 (15-16) ◽

pp. 1423-1427 ◽

Cited By ~ 14

Author(s):

Yoshifumi Fukushima ◽

Satoshi Hirayama ◽

Tsuyoshi Ueno ◽

Tomotaka Dohi ◽

Tetsuro Miyazaki ◽

...

Keyword(s):

Metabolic Syndrome ◽

Acute Coronary Syndrome ◽

Ldl Cholesterol ◽

Statin Treatment ◽

Small Dense Ldl ◽

Coronary Syndrome

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How many CCS- and ACS-patients might reach the newly recommended LDL-C-target <55mg/dl in clinical practice if guidelines were applied – an estimate from the DYSIS II study population

European Heart Journal ◽

10.1093/ehjci/ehaa946.1445 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A.K Gitt ◽

M Horack ◽

D Lautsch ◽

R Zahn ◽

J Ferrieres

Keyword(s):

Clinical Practice ◽

Real Life ◽

Statin Treatment ◽

Lipid Lowering ◽

High Risk Population ◽

High Dose ◽

Funding Source ◽

Pcsk9 Inhibitors ◽

Target Values ◽

Coronary Syndromes

Abstract Background The 2019 ESC guidelines for the management of dyslipidemia even further lowered the LDL-C-target values for the very high-risk population from <70mg/dl to <55mg/dl. Population based studies already had shown that the previous target was difficult to reach. It is yet unclear how many patients in clinical practice might be treated to the new target. Methods The Dyslipidemia International Study (DYSIS II) prospectively collected data of patients with chronic coronary syndromes (CCS) and acute coronary syndromes (ACS) (all on statins) in 18 countries in Europe, the Middle East, South- and East Asia to document patient characteristics, medication and a current lipid profile from 2012 to 2014 under real life conditions in physicians' offices and hospitals. We took these real-life lipid profiles and data on the kind/dose of used statins to estimate how treatment escalation such as changing statin treatment to a high dose (atorvastatin ≥40mg / rosuvastatin≥20mg), adding ezetimibe and adding a PCSK9-inhibitor might help to bring LDL-C-levels to the recommended <55mg/dl target. Results A total of 7,865 patients were enrolled into DYSIS II, 6,794 had CCS and 1,071 ACS. Under the documented statin treatment in DYSIS only 12.7% of patients reached an LDL-C <55mg/dl. Putting all patients on high dose statins in combination with ezetimibe, 64.1% would reach the target. If PCSK9-inhibitors would be used in the remaining patients not at goal a total of 94.0% would match the goal. Conclusion Our analysis indicates that in real life practice the use available lipid-lowering medications would substantially increase the percentage of CCS- and ACS-patients reaching the newly recommended 2019 ESC guideline LDL-C-target of <55 mg/dl from less than 20% to more than 90% of the population. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): MSD

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Coronary lesion complexity in patients with heterozygous familial hypercholesterolemia hospitalized for acute myocardial infarction: data from the RICO survey

Lipids in Health and Disease ◽

10.1186/s12944-021-01467-z ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Hermann Yao ◽

Michel Farnier ◽

Laura Tribouillard ◽

Frédéric Chague ◽

Philippe Brunel ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Ldl Cholesterol ◽

Statin Treatment ◽

Lipid Lowering ◽

Syntax Score ◽

Lipid Lowering Therapy ◽

Lipid Clinic ◽

Acute Mi ◽

Artery Disease

Abstract Background Although patients with familial heterozygous hypercholesterolemia (FH) have a high risk of early myocardial infarction (MI), the coronary artery disease (CAD) burden in FH patients with acute MI remains to be investigated. Methods The data for all consecutive patients hospitalized in 2012–2019 for an acute MI and who underwent coronary angiography were collected from a multicenter database (RICO database). FH (n = 120) was diagnosed using Dutch Lipid Clinic Network criteria (score ≥ 6). We compared the angiographic features of MI patients with and without FH (score 0–2) (n = 234) after matching for age, sex, and diabetes (1:2). Results Although LDL-cholesterol was high (208 [174–239] mg/dl), less than half of FH patients had chronic statin treatment. When compared with non-FH patients, FH increased the extent of CAD (as assessed by SYNTAX score; P = 0.005), and was associated with more frequent multivessel disease (P = 0.004), multiple complex lesions (P = 0.022) and significant stenosis location on left circumflex and right coronary arteries. Moreover, FH patients had more multiple lesions, with an increased rate of bifurcation lesions or calcifications (P = 0.021 and P = 0.036, respectively). In multivariate analysis, LDL-cholesterol levels (OR 1.948; 95% CI 1.090–3.480, P = 0.024) remained an independent estimator of anatomical complexity of coronary lesions, in addition to age (OR 1.035; 95% CI 1.014–1.057, P = 0.001). Conclusions FH patients with acute MI had more severe CAD, characterized by complex anatomical features that are mainly dependent on the LDL-cholesterol burden. Our findings reinforce the need for more aggressive preventive strategies in these high-risk patients, and for intensive lipid-lowering therapy as secondary prevention.

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Atorvastatin treatment does not abolish inflammatory mediated cardiovascular risk in subjects with chronic kidney disease

Scientific Reports ◽

10.1038/s41598-021-83273-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Renate M. Hoogeveen ◽

Simone L. Verweij ◽

Yannick Kaiser ◽

Jeffrey Kroon ◽

Hein J. Verberne ◽

...

Keyword(s):

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Cardiovascular Risk ◽

Kidney Disease ◽

Arterial Wall ◽

Ldl Cholesterol ◽

Statin Treatment ◽

Receptor Expression ◽

Disease Stage ◽

Cellular Inflammation

AbstractIndividuals with chronic kidney disease are at an increased risk for cardiovascular disease. This risk may partially be explained by a chronic inflammatory state in these patients, reflected by increased arterial wall and cellular inflammation. Statin treatment decreases cardiovascular risk and arterial inflammation in non-CKD subjects. In patients with declining kidney function, cardiovascular benefit resulting from statin therapy is attenuated, possibly due to persisting inflammation. In the current study, we assessed the effect of statin treatment on arterial wall and cellular inflammation. Fourteen patients with chronic kidney disease stage 3 or 4, defined by an estimated Glomerular Filtration Rate between 15 and 60 mL/min/1.73 m2, without cardiovascular disease were included in a single center, open label study to assess the effect of atorvastatin 40 mg once daily for 12 weeks (NTR6896). At baseline and at 12 weeks of treatment, we assessed arterial wall inflammation by 18F-fluoro-deoxyglucose positron-emission tomography computed tomography (18F-FDG PET/CT) and the phenotype of circulating monocytes were assessed. Treatment with atorvastatin resulted in a 46% reduction in LDL-cholesterol, but this was not accompanied by an attenuation in arterial wall inflammation in the aorta or carotid arteries, nor with changes in chemokine receptor expression of circulating monocytes. Statin treatment does not abolish arterial wall or cellular inflammation in subjects with mild to moderate chronic kidney disease. These results imply that CKD-associated inflammatory activity is mediated by factors beyond LDL-cholesterol and specific anti-inflammatory interventions might be necessary to further dampen the inflammatory driven CV risk in these subjects.

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