Proton pump inhibitors and statins: a possible interaction that favors low-density lipoprotein cholesterol reduction?

BACKGROUND: Proton pump inhibitors (PPIs) might influence the metabolism of cholesterol and statins in the liver. AIM: The impact of PPIs on low-density lipoprotein cholesterol (LDL-C) levels in statin-treated patients. METHODS: Retrospective observational study including consecutive statin-treated individuals followed for ≥3 years in a university hospital lipid clinic. Demographic characteristics as well as clinical and laboratory data were recorded at baseline and the most recent visit. High, moderate and low-intensity statin therapy was defined according to the expected LDL-C reduction (≥50%, 30-50%, and <30%, respectively). We compared the LDL-C reduction in subjects receiving statin + PPI with those on statin alone and assessed the overall effect of PPI administration on LDL-C lowering. RESULTS: Of 648 statin-treated subjects, 7% were also taking a PPI. There was no difference between PPI vs. non-PPI group regarding baseline characteristics and intensity of lipid-lowering therapy. Stepwise linear regression analysis showed that PPI use was significantly associated with LDL-C reduction (b =0.104, p =0.005) along with baseline LDL-C levels (b =0.482, p <0.001), treatment with ezetimibe (b =0.198, p <0.001), presence of diabetes (b =0.168, p <0.001), compliance with treatment (b =0.205, p <0.001), intensity of statin treatment (b =0.101, p =0.005) and cardiovascular risk (b =0.082, p =0.049). Subjects receiving statin + PPI had a higher LDL-C reduction by 6.4% compared with those taking a statin alone (fully adjusted p =0.005). CONCLUSIONS: PPIs may modestly boost the statin-mediated LDL-C reduction. This effect should be confirmed by prospective clinical studies. Hippokratia 2015; 19 (4): 332-337.

Modelling eating practices in non-fatal acute coronary syndrome or stroke development: a case/case-control study.

BACKGROUND AND AIMS: Although significant evidence exists regarding the role of specific foods and dietary patterns on the development of cardiovascular disease, the influence of eating practices has not been thoroughly examined and understood. The aim of the present work was to evaluate the independent role of eating practices on the likelihood of developing an acute coronary syndrome (ACS) or ischemic stroke. METHODS AND RESULTS: During 2009-2010, 1000 participants were enrolled; 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke and 500 were population-based control subjects (250 age-sex matched one-for-one with ACS patients, and 250 age-sex matched one-for-one with stroke patients). Eating practices were evaluated using a special questionnaire. Socio-demographic, clinical, psychological, dietary and other lifestyle characteristics were also measured. After controlling for potential confounding factors, each 20 min prolongation of dinner-to-sleep time was associated with 10% lower likelihood of ischemic stroke (95%CI: 0.83-0.98). Furthermore, eating practices related to stress (i.e., eating while being stressed, eating while working at the same time, skipping a meal due to work obligations) were associated with higher likelihood of having an ACS. Finally, eating while watching television was associated with lower likelihood of having an ACS (OR: 0.46, 95%CI: 0.27-0.78) or stroke event (OR: 0.42, 95%CI: 0.23-0.77). CONCLUSION: Results of this work, present novel information, indicating the significance of eating practices, in addition to dietary patterns, regarding the development of coronary heart disease and stroke, and could be used in the primary prevention of CVD.

Distinct effects of fixed combinations of valsartan with either amlodipine or hydrochlorothiazide on lipoprotein subfraction profile in patients with hypertension.

The effect of antihypertensive drugs on lipoprotein subfraction profile is still under investigation. In this study the effects of fixed combination of valsartan with either amlodipine (V-A) or hydrochlorothiazide (V-H) on low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) subfraction profile of patients with stage 2 or 3 hypertension were assessed. A total of 60 drug-naive patients were randomized to either V-A (160/5 mg, n=30) or V-H (160/12.5 mg, n=30). At baseline as well as 16 weeks post-treatment analysis of the LDL and HDL subfraction profile was conducted by using LDL Lipoprint System. Both V-A and V-H effectively reduced blood pressure (BP) to similar levels. An increase in the cholesterol concentration of small-dense LDL subfractions (by 18.2%, P<0.05) was observed in the V-H group, whereas this parameter remained unchanged in the V-A group. Therefore, mean LDL particle size was decreased in the V-H group (from 267 ± 5 to 266 ± 5Å, P<0.05). HDL-Cholesterol (HDL-C) levels were reduced by 4.7% (P<0.05) in the V-H group, mirrored by a reduction in the cholesterol mass of small and intermediate HDL particles. In conclusion, despite similar reductions in BP, V-H combination may adversely affect serum lipids as well as LDL and HDL subfraction profile as compared with V-A.

Effect of rosuvastatin monotherapy or in combination with fenofibrate or ω-3 fatty acids on lipoprotein subfraction profile in patients with mixed dyslipidaemia and metabolic syndrome.

BACKGROUND: Raised triglycerides (TG), decreased high-density lipoprotein cholesterol (HDL-C) levels and a predominance of small dense low density lipoproteins (sdLDL) are characteristics of the metabolic syndrome (MetS). OBJECTIVE: To compare the effect of high-dose rosuvastatin monotherapy with moderate dosing combined with fenofibrate or ω-3 fatty acids on the lipoprotein subfraction profile in patients with mixed dyslipidaemia and MetS. METHODS: We previously randomised patients with low-density lipoprotein cholesterol (LDL-C) > 160 and TG > 200 mg/dl to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or ω-3 fatty acids 2 g/day (Rω group, n = 30). In the present study, only patients with MetS were included (24, 23 and 24 in the R, RF and Rω groups respectively). At baseline and after 12 weeks of treatment, the lipoprotein subfraction profile was determined by polyacrylamide 3% gel electrophoresis. RESULTS: The mean LDL size was significantly increased in all groups. This change was more prominent with RF than with other treatments in parallel with its greater hypotriglyceridemic capacity (p < 0.05 compared with R and Rω). A decrease in insulin resistance by RF was also noted. Only RF significantly raised HDL-C levels (by 7.7%, p < 0.05) by increasing the cholesterol of small HDL particles. The cholesterol of larger HDL subclasses was significantly increased by R and Rω. CONCLUSIONS: All regimens increased mean LDL size; RF was the most effective. A differential effect of treatments was noted on the HDL subfraction profile.

Comparison of the effects of simvastatin vs. rosuvastatin vs. simvastatin/ezetimibe on parameters of insulin resistance.

BACKGROUND: Statin treatment may be associated with adverse effects on glucose metabolism. Whether this is a class effect is not known. In contrast, ezetimibe monotherapy may beneficially affect insulin sensitivity. OBJECTIVE: The aim of this study was to compare the effects of three different regimens of equivalent low-density lipoprotein cholesterol (LDL-C) lowering capacity on glucose metabolism. METHODS: A total of 153 patients (56 men), who had not achieved the LDL-C goal recommended by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) despite a 3-month dietary and lifestyle intervention, were randomly allocated to receive open-label simvastatin 40 mg or rosuvastatin 10 mg or simvastatin/ezetimibe 10/10 mg for 12 weeks. The primary end point was changes in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary endpoints consisted of changes in fasting insulin levels, fasting plasma glucose (FPG), glycosylated haemoglobin (HbA(1c) ), the HOMA of ß-cell function (HOMA-B) (a marker of basal insulin secretion by pancreatic ß-cells), LDL-C and high sensitivity C reactive protein (hsCRP). RESULTS: At week 12, all three treatment regimens were associated with significant increases in HOMA-IR and fasting insulin levels (p < 0.05 compared with baseline). No significant difference was observed between groups. No change in FPG, HbA(1c) and HOMA-B levels compared with baseline were noted in any of the three treatment groups. Changes in serum lipids and hsCRP were similar across groups. CONCLUSION: To the extent that simvastatin 40 mg, rosuvastatin 10 mg and simvastatin/ezetimibe 10/10 mg are associated with adverse effects on insulin resistance, they appear to be of the same magnitude.

Rosuvastatin treatment is associated with an increase in insulin resistance in hyperlipidaemic patients with impaired fasting glucose.

AIM OF THE STUDY: The increase in physician-reported diabetes following rosuvastatin treatment in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin study has raised concerns whether this statin exerts a detrimental effect on glucose metabolism. We assessed the effect of rosuvastatin treatment across dose range on glucose homeostasis in hyperlipidaemic patients with impaired fasting glucose (IFG), who are at high risk to develop diabetes mellitus. METHODS: The medical records of 72 hypelipidaemic patients with IFG on rosuvastatin 10 (RSV10 group), 20 (RSV20 group) and 40 mg/day (RSV40 group) were reviewed. The median follow up was 12.4 weeks. At the first visit, prior to rosuvastatin prescription and at the latest visit, serum lipid profile and indices of glucose metabolism, including fasting glucose, insulin and HOmeostasis Model Assessment (HOMA(IR)) index levels, were assessed. RESULTS: Rosuvastatin treatment improved lipid profile and was associated with a dose-dependent significant increase in HOMA(IR) values by 25.4%, 32.3% and 44.8% at the dose of 10, 20 and 40 mg/day (p < 0.01 for all, p < 0.05 for the comparison between groups), respectively, mirrored by correspondent increase in plasma insulin levels [by 21.7%, 25.7% and 46.2% in the RSV10, RSV20 and RSV40 group (p < 0.001 for all) respectively]. Baseline HOMA(IR) levels was the most important contributor (R(2) = 68.1%, p < 0.001), followed by the dose of rosuvastatin treatment (R(2) = 23.7%, p < 0.01), in a model that explained 91.8% of the variability in HOMA(IR) increase. CONCLUSION: In patients with IFG and hyperlipidaemia, rosuvastatin treatment was associated with a dose-dependent increase in insulin resistance.

The effects of orlistat and fenofibrate, alone or in combination, on high-density lipoprotein subfractions and pre-beta1-HDL levels in obese patients with metabolic syndrome.

OBJECTIVE: We assessed the effect of orlistat and fenofibrate, alone or in combination, on plasma high-density lipoprotein (HDL) subfractions and plasma pre-beta1-HDL levels in overweight and obese subjects with metabolic syndrome (MetS). METHODS: Patients (n = 89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200 mg/day (F group) or both (OF group) for 6 months. HDL subfractions were determined using a polyacrylamide gel tube electrophoresis method and pre-beta1-HDL levels using enzyme-linked immunoabsorbent assay. RESULTS: We observed a significant change of high-density lipoprotein cholesterol (HDL-C) levels only in the F group (+3%, p < 0.05). Large HDL-C levels were significantly increased and small HDL-C levels were significantly reduced with O administration. In F group we observed a significant increase of small HDL-C levels. No significant change of large or small HDL-C levels was observed with combination treatment. We observed a significant increase of pre-beta1-HDL levels in all groups, which was significantly greater in OF group compared with O or F monotherapy. CONCLUSION: OF combination increased the antiatherogenic pre-beta1-HDL levels in overweight and obese patients with MetS. Furthermore, OF combination counterbalanced the reduction of small HDL-C levels observed with orlistat monotherapy.

Different definitions of the metabolic syndrome and risk of first-ever acute ischaemic non-embolic stroke in elderly subjects.

To investigate which of the three recently proposed definitions of the metabolic syndrome (MetS) is related to the excessive risk of ischaemic non-embolic stroke in elderly individuals, and thus may be more appropriate to implement in clinical practice. In a population-based case-control study of subjects aged older than 70 years (163 patients vs. 166 controls), we evaluated the association of first-ever acute ischaemic non-embolic stroke with the MetS defined by using recent definitions as proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF) and the National Heart, Lung and Blood Institute/American Heart Association (NHLBI/AHA). By applying the NCEP ATP III, NHLBI/AHA and IDF definitions, the prevalence of MetS in the patient group was 46%, 57.1% and 69.9%, respectively, compared with 15.7%, 18.1% and 30.7% in the control group (p < 0.001 for all comparisons). After adjusting for multiple risk factors, the odds ratio (OR) for ischaemic stroke was 2.59 [95% confidence interval (CI): 1.24-5.42, p = 0.012] for NCEP ATP III-defined MetS and 3.18 (95% CI: 1.58-6.39, p = 0.001) for NHLBI/AHA-defined MetS. However, the association of IDF-defined MetS with ischaemic stroke was not significant (OR 1.18, 95% CI: 0.50-2.78, p = 0.71). The implementation of the IDF (unlike NCEP ATP III and NHLBI/AHA) MetS definition substantially increases the number of elderly subjects labelled as having MetS without contributing to the identification of those at high risk of stroke.

Do statins have an antiarrhythmic activity?

Sudden cardiac death, which is mainly associated with the presence of life-threatening ventricular arrhythmias, is a common 'killer' among patients with coronary artery disease. Moreover, atrial fibrillation is the most common arrhythmia encountered in the clinical practice. The beneficial effect of statins on cardiovascular morbidity and mortality is well-established, while the exact role of this class of drugs against arrhythmias remains unclear. This review discusses the effect of statin treatment on arrhythmias that are commonly seen in the clinical setting. The underlying pathophysiological mechanisms are also overviewed. Compelling evidence from the majority of the studies reviewed shows that statins exhibit a protective effect against the occurrence of ventricular arrhythmias and atrial fibrillation.