CPAP Intervention as an Add-On Treatment to Lipid-Lowering Medication in Coronary Artery Disease Patients with Obstructive Sleep Apnea in the RICCADSA Trial

Dyslipidaemia is a well-known risk factor for coronary artery disease (CAD), and reducing lipid levels is essential for secondary prevention in management of these high-risk individuals. Dyslipidaemia is common also in patients with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) is the first line treatment of OSA. However, evidence of a possible lipid-lowering effect of CPAP in CAD patients with OSA is scarce. We addressed the effect of CPAP as an add-on treatment to lipid-lowering medication in a CAD cohort with concomitant OSA. This study was a secondary analysis of the RICCADSA trial (Trial Registry: ClinicalTrials.gov; No: NCT 00519597), that was conducted in Sweden between 2005 and 2013. In total, 244 revascularized CAD patients with nonsleepy OSA (apnea–hypopnea index ≥ 15/h, Epworth Sleepiness Scale score < 10) were randomly assigned to CPAP or no-CPAP. Circulating triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels (all in mg/dL) were measured at baseline and 12 months after randomization. The desired TG levels were defined as circulating TG < 150 mg/dL, and LDL levels were targeted as <70 mg/dL according to the recent guidelines of the European Cardiology Society and the European Atherosclerosis Society. A total of 196 patients with available blood samples at baseline and 12-month follow-up were included (94 randomized to CPAP, 102 to no-CPAP). We found no significant between-group differences in circulating levels of TG, TC, HDL and LDL at baseline and after 12 months as well as in the amount of change from baseline. However, there was a significant decline regarding the proportion of patients with the desired TG levels from 87.2% to 77.2% in the CPAP group (p = 0.022), whereas there was an increase from 84.3% to 88.2% in the no-CPAP group (n.s.). The desired LDL levels remained low after 12 months in both groups (15.1% vs. 17.2% in CPAP group, and 20.8% vs. 18.8% in no-CPAP group; n.s.). In a multiple linear regression model, the increase in the TG levels was predicted by the increase in body-mass-index (β = 4.1; 95% confidence interval (1.0–7.1); p = 0.009) adjusted for age, sex and CPAP usage (hours/night). CPAP had no lipid-lowering effect in this revascularized cohort with OSA. An increase in body-mass-index predicted the increase in TG levels after 12 months, suggesting that lifestyle modifications should be given priority in adults with CAD and OSA, regardless of CPAP treatment.

Relationship between genetic polymorphism of drug transporters and the efficacy of Rosuvastatin, atorvastatin and simvastatin in patients with hyperlipidemia

Background To determine the effect of genetic polymorphism of drug transporters on the efficacy of treatment with Rosuvastatin, Atorvastatin and Simvastatin in patients with hyperlipidemia. Methods The study consists of 180 patients, aged 40–75 years, with hyperlipidemia. All patients were divided into two equal groups: patients with different SLCO1B1 (521CC, 521CT and 521TT) and MDR1 (3435CC, 3435TC and 3435TT) genotypes. Each group was divided into rosuvastatin-treated, atorvastatin-treated and simvastatin-treated subgroups. The lipid-lowering effect of statins was assessed by tracing changes in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. Results The use of statins over a 4-month period led to substantial reductions in TC and LDL-C levels. The hypolipidemic effect of studied agents was seen in both groups. However, it was less pronounced in patients with 521CC genotype. No statistically significantly differences were found between carriers of 3435TT, 3435CT and 3435CC genotypes. Conclusions The lipid-lowering efficacy of rosuvastatin was higher compared to other two statins. Patients with SLCO1B1 521CC genotype are more likely to encounter a decrease in the hypolipidemic effect of statins. Such a risk should be considered when treating this category of patients. MDR1 polymorphism had no significant effect on statin efficacy.

Rosmarinic Acid Exhibits a Lipid-Lowering Effect by Modulating the Expression of Reverse Cholesterol Transporters and Lipid Metabolism in High-Fat Diet-Fed Mice

Hyperlipidemia is a potent risk factor for the development of cardiovascular diseases. The reverse cholesterol transport (RCT) process has been shown to alleviate hyperlipidemia and protect against cardiovascular diseases. Recently, rosmarinic acid was reported to exhibit lipid-lowering effects. However, the underlying mechanism is still unclear. This study aims to investigate whether rosmarinic acid lowers lipids by modulating the RCT process in high-fat diet (HFD)-induced hyperlipidemic C57BL/6J mice. Our results indicated that rosmarinic acid treatment significantly decreased body weight, blood glucose, and plasma total cholesterol and triglyceride levels in HFD-fed mice. Rosmarinic acid increased the expression levels of cholesterol uptake-associated receptors in liver tissues, including scavenger receptor B type 1 (SR-B1) and low-density lipoprotein receptor (LDL-R). Furthermore, rosmarinic acid treatment notably increased the expression of cholesterol excretion molecules, ATP-binding cassette G5 (ABCG5) and G8 (ABCG8) transporters, and cholesterol 7 alpha-hydroxylase A1 (CYP7A1) as well as markedly reduced cholesterol and triglyceride levels in liver tissues. In addition, rosmarinic acid facilitated fatty acid oxidation through AMP-activated protein kinase (AMPK)-mediated carnitine palmitoyltransferase 1A (CPT1A) induction. In conclusion, rosmarinic acid exhibited a lipid-lowering effect by modulating the expression of RCT-related proteins and lipid metabolism-associated molecules, confirming its potential for the prevention or treatment of hyperlipidemia-derived diseases.

Lipid-Lowering Bioactivity of Microalga Nitzschia laevis Extract Containing Fucoxanthin in Murine Model and Carcinomic Hepatocytes

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is one of the most common liver diseases worldwide. So far, no definitive medical treatment has been established to treat NAFLD except for lifestyle medication. Nitzschia laevis extract (NLE), a microalgal extract rich in fucoxanthin, has been previously demonstrated to reduce bodyweight in high-fat-diet (HFD) C57BL/6J mice, indicating potential for prevention of NAFLD. In the present study, we investigated the lipid-lowering effects of NLE in HFD-induced steatosis murine model and palmitate-treated HepG2 cells. The results showed that NLE significantly lowered inguinal fat and attenuated hepatic steatosis in C57BL/6J mice. Especially, NLE significantly prevented lipid accumulation in HepG2 cells. This was probably due to its capability to enhance hepatic mitochondrial function as evidenced by the increased oxygen consumption rate (OCR) and mitochondrial membrane potential (MMP), and repress fatty acid synthesis through phosphorylation of acetyl-CoA carboxylase (ACC). Moreover, fucoxanthin was identified to be responsible for the lipid-lowering effect of NLE. Taken together, NLE or other microalgal fucoxanthin-rich products are promising natural products that may help prevent against NAFLD.

Sudden Fall in the Lipid-Lowering Effect of Evolocumab: The Butler Is Not Always Guilty

A 78-year-old man came to our attention after undergoing coronary computed tomography angiography documenting multivessel coronary artery disease. He was started on treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab 140 mg subcutaneously every 2 weeks. Treatment-emergent changes in lipids and lipoproteins were long-lasting, and the medication was well tolerated by the patient in the long-term. Unexpectedly, after 2 years of continuous treatment with evolocumab, serum lipids increased, apparently without any reasonable explanation. During the follow-up visit, the patient was found to have habitually injected evolocumab into his right thumb instead of into the appropriate injection sites (i.e., abdomen, thighs or upper arms) after turning the injector upside down.

Sudden Fall in the Lipid-Lowering Effect of Evolocumab: The Butler Is Not Always Guilty

A 78-year-old man came to our attention after undergoing coronary computed tomography angiography documenting multivessel coronary artery disease. He was started on treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab 140 mg subcutaneously every 2 weeks. Treatment-emergent changes in lipids and lipoproteins were long-lasting, and the medication was well tolerated by the patient in the long-term. Unexpectedly, after 2 years of continuous treatment with evolocumab, serum lipids increased, apparently without any reasonable explanation. During the follow-up visit, the patient was found to have habitually injected evolocumab into his right thumb instead of into the appropriate injection sites (i.e., abdomen, thighs or upper arms) after turning the injector upside down.

Effect of statins on post-contrast acute kidney injury: a multicenter retrospective observational study

Background Post-contrast acute kidney injury (PC-AKI) is a severe complication of coronary angiography (CAG) and percutaneous coronary intervention (PCI). Currently, the effect of statins on PC-AKI and its mechanism remains unclear. Methods This multicenter retrospective observational study included 4386 patients who underwent CAG or PCI from December 2006 to December 2019 in Sir Run Run Shaw Hospital and its medical consortium hospitals. Serum creatinine pre- or post-procedure within 72 h after PCI was recorded. Multivariate logical regression was used to explore whether preoperative use of statins was protective from PC-AKI. The path analysis model was then utilized to look for the mediation factors of statins. Results Four thousand three hundred eighty-six patients were enrolled totally. The median age of the study population was 68 years old, 17.9% with PC-AKI, and 83.3% on preoperative statins therapy. The incidence of PC-AKI was significantly lower in group of patients on statins therapy. Multivariate regression indicated that preoperative statins therapy was significantly associated with lower percentage of elevated creatinine (β: -0.118, P < 0.001) and less PC-AKI (OR: 0.575, P < 0.001). In the preoperative statins therapy group, no statistically significant difference was detected between the atorvastatin and rosuvastatin groups (OR: 1.052, P = 0.558). Pathway model analysis indicated a direct protective effect of preoperative statins therapy on PC-AKI (P < 0.001), but not through its lipid-lowering effect (P = 0.277) nor anti-inflammatory effect (P = 0.596). Furthermore, it was found that “low-density lipoprotein cholesterol (LDL-C)→C-reactive protein (CRP)” mediated the relationship between preoperative statins therapy and PC-AKI (P = 0.007). However, this only explained less than 1% of the preoperative protective effects of statins on PC-AKI. Conclusion Preoperative statins therapy is an independent protective factor of PC-AKI, regardless of its type. This protective effect is not achieved by lipid-lowering effect or anti-inflammatory effect. These findings underscore the potential use of statins in preventing PC-AKI among those at risk.

Transcriptome and translatome analyses reveal the regulatory role of betaine in high fat diet (HFD)-induced hepatic steatosis

Non-alcoholic fatty liver disease (NAFLD) is a common disease with a multitude of complications. Increasing evidence shows that the dietary supplement with betaine, a natural chemical molecule, can effectively reduce the fat accumulation in the liver. Translational regulation is considered to play a vital role in gene expression, but whether betaine functions through the regulation of gene translational level is still unclear. To this end, RNC-seq (ribosome-nascent chain complex bound mRNA sequencing) and RNA-seq co-analyses were performed to identify betaine target genes by using the liver samples from high-fat diet + betaine treated and high-fat diet treated mice. The results showed that betaine does play a lipid-lowering role by regulating the expression of gene translation levels; some NAFLD- and lipid metabolism- associated genes were differentially expressed at translational level, for example. And the mRNA translation ratio (TR) of gene significantly increased after betaine treatment. Besides, it is found that the regulation of some genes at transcriptional level is opposite to that at translational level, which indicates that transcriptional regulation and translational regulation may be independent from each other. Finally, we identified several candidate genes, especially Gpc1 , which may mediate the lipid-lowering effect of betaine in the liver. To sum up, this study depicted the molecular portrait of mice liver with or without betaine treatment from the angel of translatome and transcriptome, giving insights into the molecular mechanism of betaine-mediated lipid-lowering effect and also providing new clues for understanding and prevention of NAFLD.