Statins Abstracts 2


Berberis aristata/Silybum marianum fixed combination (Berberol(®)) effects on lipid profile in dyslipidemic patients intolerant to statins at high dosages: a randomized, placebo-controlled, clinical trial.
            (Derosa et al., 2015) Download
AIM:  to evaluate the efficacy of Berberis aristata/Silybum marianum (Berberol(®)) in a sample of dyslipidemic patients intolerant to statins at high dosages in a randomized, double blind, placebo-controlled clinical trial. METHODS:  we enrolled 175 euglycemic, dyslipidemic subjects, intolerant to statins at high dosages. During the run-in period, statins were stopped for 1 month, then they were re-introduced at the half of the previously taken dose. After that, patients were randomized to placebo or Berberol(®), 1 tablet during the lunch and 1 tablet during the dinner, for 6 months. Anthropometric, metabolic and inflammatory parameters were assessed at randomization, at 3 and 6 months. RESULTS:  fasting plasma glucose, insulin, and HOMA-index levels were reduced by Berberol(®), but not by placebo; moreover they were lower than the ones recorded with placebo. Total cholesterol, LDL-C, triglycerides, and myeloperoxidase did not change after 6 months since the reduction of statin dosage and the introduction of Berberol(®), while they increased in the placebo group, and were higher compared to the ones obtained with active treatment. No patients had serious adverse events in both groups. CONCLUSIONS:  our study displays the rationale of the combination of Berberol(®) and a reduced dosage of statin for the treatment of hyperlipidemia in patients intolerant to statins at high dosage.

Statin treatment alters serum n-3 and n-6 fatty acids in hypercholesterolemic patients.
            (Harris et al., 2004) Download
Statins are highly effective cholesterol-lowering drugs but may have broader effects on metabolism. This investigation examined effects of simvastatin on serum levels of n-6 and n-3 polyunsaturated fatty acids (PUFAs). Subjects were 106 healthy adults with hypercholesterolemia randomly assigned to receive placebo or 40 mg simvastatin daily for 24 weeks. Serum fatty acids were analyzed by gas chromatography. Total fatty acid concentration fell 22% in subjects receiving simvastatin (P<.001), with similar declines across most fatty acids. However, concentrations of arachidonic acid (AA, 20:4n-6), eicosapentanoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were unchanged. Relative percentages of linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (LNA, 18:3n-3), decreased while AA and DHA increased (P's < or = .007). In addition, simvastatin increased the AA:EPA ratio from 15.5 to 18.8 (P<.01), and tended to increase the AA:DHA ratio (P=.053). Thus, simvastatin lowered serum fatty acid concentrations while also altering the relative percentages of important PUFAs.

Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).
            (Issa et al., 2018) Download
IMPORTANCE:  In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials. OBJECTIVE:  To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT. DESIGN:  TACT was a factorial trial testing chelation treatments and a 28-component high-dose oral multivitamins and multiminerals regimen versus placebo in post-myocardial infarction (MI) patients 50 years or older. PARTICIPANTS:  There were 460 (27%) of 1,708 TACT participants not taking statins at baseline, 224 (49%) were in the active vitamin group and 236 (51%) were in the placebo group. SETTING:  Patients were enrolled at 134 sites around the United States and Canada. INTERVENTION:  Daily high-dose oral multivitamins and multiminerals (6 tablets, active or placebo). MAIN OUTCOME:  The primary end point of TACT was time to the first occurrence of any component of the composite end point: all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for angina. RESULTS:  The primary end point occurred in 137 nonstatin participants (30%), of which 51 (23%) of 224 were in the active group and 86 (36%) of 236 were taking placebo (hazard ratio, 0.62; 95% confidence interval, 0.44-0.87; P=.006). Results in the key TACT secondary end point, a combination of cardiovascular mortality, stroke, or recurrent MI, was consistent in favoring the active vitamin group (hazard ratio, 0.46; 95% confidence interval, 0.28-0.75; P=.002). Multiple end point analyses were consistent with these results. CONCLUSION AND RELEVANCE:  High-dose oral multivitamin and multimineral supplementation seem to decrease combined cardiac events in a stable, post-MI population not taking statin therapy at baseline. These unexpected findings are being retested in the ongoing TACT2.


Effects of extended-release niacin on the postprandial metabolism of Lp(a) and ApoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus.
            (Ooi et al., 2015) Download
OBJECTIVE:  The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration. APPROACH AND RESULTS:  The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87% fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5%) and the production rates of apo(a) (-41.5%) and Lp(a)-apoB-100 (-32.1%); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7%), intermediate-density lipoprotein (-33.6%), and LDL (-18.3%) apoB-100 concentrations and the corresponding production rates (VLDL, -49.8%; intermediate-density lipoprotein, -44.7%; LDL, -46.1%). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9%). CONCLUSIONS:  In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN.

Effect of niacin on triglyceride-rich lipoprotein apolipoprotein B-48 kinetics in statin-treated patients with type 2 diabetes.
            (Pang et al., 2016) Download
AIM:  To investigate the effects of extended-release (ER) niacin on apolipoprotein B-48 (apoB-48) kinetics in statin-treated patients with type 2 diabetes (T2DM). METHODS:  A total of 12 men with T2DM were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed to the alternate therapy. Postprandial metabolic studies were performed at the end of each treatment period. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. ApoB-48 kinetics were determined using stable isotope tracer kinetics with fractional catabolic rates (FCRs) and secretion rates derived using a non-steady-state compartmental model. Area-under-the-curve (AUC) and incremental AUC (iAUC) for plasma triglyceride and apoB-48 were also calculated over the 10-h period after ingestion of the fat meal. RESULTS:  In statin-treated patients with T2DM, apoB-48 concentration was lower with ER niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/l, p = 0.03) compared with statin alone. Postprandial triglyceride and apoB-48 AUC were also significantly lower on ER niacin treatment (-15 and -26%, respectively; p < 0.05), without any change to triglyceride and apoB-48 iAUC. ApoB-48 secretion rate in the basal state (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p = 0.04) and number of apoB-48-containing particles secreted in response to the fat load (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p = 0.02) were lower on ER niacin. ApoB-48 FCR was not altered with ER niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p = 0.79). CONCLUSIONS:  ER niacin reduces apoB-48 concentration by lowering fasting and postprandial apoB-48 secretion rate. This effect may be beneficial for lowering atherogenic postprandial lipoproteins and may provide cardiovascular disease risk benefit in patients with T2DM.

Effects of vitamin D on plasma lipid profiles in statin-treated patients with hypercholesterolemia: A randomized placebo-controlled trial.
            (Qin et al., 2015) Download
BACKGROUND & AIMS:  Lipid abnormalities are regarded as a risk factor for cardiovascular disease. Low vitamin D status has been shown to be associated with hyperlipidemia. We planned to research the effects of vitamin D supplementation as an adjuvant therapy for patients with hypercholesterolemia. METHODS:  Patients with hypercholesterolemia were enrolled in this single-center, double-blind, placebo-controlled trial in Beijing (39°54' N). Fifty-six patients were randomly assigned to receive vitamin D (n = 28, 2000 IU/d) or a placebo (n = 28) as an add-on to statin, by the method of permutated block randomization. Serum lipid levels were evaluated at baseline, 1, 3 and 6 months. RESULTS:  Vitamin D supplementation resulted in increased serum 25-hydroxyvitamin D concentrations compared with placebo (+16.3 ± 11.4 compared with +2.4 ± 7.1 ng/ml; p < 0.001). At 6 months, the primary end point, a difference in the fall of serum total cholesterol levels between the vitamin D and placebo groups after 6 months of treatment was significant -22.1 mg/dl (95% CI -32.3; -12.2) (p < 0.001). The difference between the groups in the fall of serum triglyceride levels after 6 months of treatment was -28.2 mg/dl (95% CI -48.8; -8.4) (p < 0.001). In patients with 25-hydroxyvitamin D level<30 ng/ml at baseline (n = 43), the serum total cholesterol and triglyceride levels were reduced by -28.5 ± 11.9 mg/dl (p < 0.001) and -37.1 ± 19.5 mg/dl (p < 0.001), respectively. CONCLUSIONS:  Vitamin D supplementation might improve serum lipid levels in statin-treated patients with hypercholesterolemia, it might be an adjuvant therapy for patients with hypercholesterolemia. Clinical Trials Registration Number - NCT02009787.


Do lipid-lowering drugs cause erectile dysfunction? A systematic review
            (Rizvi et al., 2002) Download
BACKGROUND: Erectile dysfunction (ED) is common although under-reported by patients. Along with the better known causes of ED, drug-induced impotence needs to be considered as a cause of this symptom. Lipid-lowering drugs have been prescribed increasingly. Their relationship to ED is controversial. OBJECTIVES: Our aim was to clarify the relationship between lipid-lowering therapy and ED. A secondary aim was to assess the value of the systematic review procedure in the area of adverse drug reactions. METHODS: A systematic review was carried out using computerized biomedical databases and Internet sources. Terms denoting ED were linked with terms referring to lipid-lowering drugs. Information was also sought from regulatory agencies. RESULTS: A significant literature was identified, much from obscure sources, which included case reports, review articles, and information from clinical trials and from regulatory agencies. Information from all of these sources identified fibrates as a source of ED. A substantial number of cases of ED associated with statin usage have been reported to regulatory agencies. Case reports and clinical trial evidence supported the suggestion that statins can also cause ED. Some information on possible mechanisms was obtained, but the mechanism remains uncertain. CONCLUSIONS: The systematic review procedure was applied successfully to collect evidence suggesting that both statins and fibrates may cause ED. More numerous reports to regulatory agencies complemented more detailed information from case reports to provide a new perspective on a common area of prescribing.

The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials
            (Schooling et al., 2013) Download
BACKGROUND: Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins' pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone. METHODS: A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using '(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)' restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. RESULTS: Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13). CONCLUSIONS: Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here

Creatine supplementation prevents statin-induced muscle toxicity.
            (Shewmon and Craig, 2010) Download
Objective: To determine whether creatine supplementation would diminish the severity of statin-induced myalgia, weakness, and cramping. Methods: We conducted an open-labeled case series of creatine supplementation in 12 patients with known intolerance to at least 3 statins, and we created controls by starting, withdrawing, and restart- ing creatine treatment during statin therapy. Myopathy scores were significantly higher after the statin-only treatment phase than at baseline but did not differ from baseline after the other treatment phases. Creatine loading plus maintenance creatine therapy prevented myopathy symp- toms in 8 of 10 patients receiving statins. After these 8 patients stopped maintenance creatine therapy and developed myopathy symptoms while receiving statins alone, reloading creatine decreased symptoms to baseline levels. Also, increasing the creatine dosage from maintenance to loading diminished myopathy symp- toms to baseline levels in 1 patient who developed symptoms 6 days after a statin was added to maintenance creatine therapy.

Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy.
            (Silva et al., 2007) Download
BACKGROUND:  Randomized trials evaluating intensive dose statin therapy have found enhanced protection against cardiovascular (CV) events compared with moderate-dose statin therapy in patients with acute coronary syndromes (ACS) or stable coronary artery disease (CAD). However, the potential for an increase in the risk of drug-induced adverse events with such therapy has not been quantified. OBJECTIVE:  This meta-analysis was performed to compare the incremental risks associated with intensive- and moderate-dose statin therapy. METHODS:  MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1995 to 2006 using the following terms: acute, coronary syndrome, stable coronary artery disease, atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, and fluvastatin. Prospective, randomized controlled trials evaluating intensive- and moderate-dose statin therapy for the reduction of CV events were included in the review. The safety end points examined were elevations in creatine kinase (CK) >or= 10 times the upper limit of normal (ULN), elevations in alanine or aspartate aminotransferase >or=3 times the ULN, rhabdomyolysis, drug-induced adverse events requiring discontinuation of therapy, and any drug-induced events. The efficacy end points examined were all-cause mortality, CV death, nonfatal myocardial infarction (MI), and stroke. Each analysis compared the effect of intensive- or moderate-dose statin therapy on statin-induced adverse events and clinical efficacy outcomes. Simple absolute risk, the number needed to treat, and the number needed to harm were also calculated to quantify the incremental benefit or harm associated with intensive-dose statin therapy. RESULTS:  Four trials were included in the analysis.Together, they included 27,548 patients with ACS or stable CAD followed for a mean of 3.4 years, representing 108,049 patient-years of clinical-trial experience. Intensive-dose therapy with atorvastatin or simvastatin 80 mg was associated with a significant increase in the risk for any adverse event (odds ratio [OR] = 1.44; 95% CI, 1.33-1.55; P < 0.001) and adverse events requiring discontinuation of therapy (OR = 1.28; 95% CI, 1.18-1.39; P < 0.001). Intensive-dose therapy also was associated with an increased risk for abnormalities on liver function testing (OR = 4.48; 95% Cl, 3.27-6.16; P < 0.001) and elevations in CK (OR = 9.97; 95% CI, 1.28-77.92; P = 0.028). The benefits of intensive-dose statin therapy included reductions in CV death (OR = 0.86; 95% CI, 0.75-0.99; P = 0.031), MI (OR = 0.84; 95% CI, 0.76-0.93; P < 0.001), and stroke (OR = 0.82; 95% CI, 0.72-0.94; P = 0.004). CONCLUSIONS:  Although intensive-dose statin therapy was associated with a reduced risk for important CV events, it was also associated with an increased risk for statin-induced adverse events. Therefore, moderate-dose statin therapy may be the most appropriate choice for achieving CV risk reduction in the majority of individuals, whereas intensive-dose statin therapy may be reserved for those at highest risk.

Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study.
            (Skarlovnik et al., 2014) Download
BACKGROUND:  Statin use is frequently associated with muscle-related symptoms. Coenzyme Q10 supplementation has yielded conflicting results in decreasing statin myopathy. Herein, we tested whether coenzyme Q10 supplementation could decrease statin-associated muscular pain in a specific group of patients with mild-to-moderate muscle symptoms. MATERIAL/METHODS:  Fifty patients treated with statins and reporting muscle pain were recruited. The Q10 group (n=25) received coenzyme Q10 supplementation over a period of 30 days (50 mg twice daily), and the control group (n=25) received placebo. The Brief Pain Inventory (BPI) questionnaire was used and blood testing was performed at inclusion in the study and after 30 days of supplementation. RESULTS:  The intensity of muscle pain, measured as the Pain Severity Score (PSS), in the Q10 group was reduced from 3.9±0.4 to 2.9±0.4 (P<0.001). The Pain Interference Score (PIS) after Q10 supplementation was reduced from 4.0±0.4 to 2.6±0.4 (P<0.001). In the placebo group, PSS and PIS did not change. Coenzyme Q10 supplementation decreased statin-related muscle symptoms in 75% of patients. The relative values of PSS and PIS significantly decreased (-33.1% and -40.3%, respectively) in the Q10 group compared to placebo group (both P<0.05). From baseline, no differences in liver and muscle enzymes or cholesterol values were found. CONCLUSIONS:  The present results show that coenzyme Q10 supplementation (50 mg twice daily) effectively reduced statin-related mild-to-moderate muscular symptoms, causing lower interference of statin-related muscular symptoms with daily activities.

Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients.
            (Yadav et al., 2015) Download
BACKGROUND:  The aim of this study was to explore the influence of extended-release niacin/laropiprant (ERN/LRP) versus placebo on high-density lipoprotein (HDL) antioxidant function, cholesterol efflux, apolipoprotein B100 (apoB)-containing lipoproteins, and mediators of vascular inflammation associated with 15% increase in high-density lipoprotein cholesterol (HDL-C). Study patients had persistent dyslipidemia despite receiving high-dose statin treatment. METHODS AND RESULTS:  In a randomized double-blind, placebo-controlled, crossover trial, we compared the effect of ERN/LRP with placebo in 27 statin-treated dyslipidemic patients who had not achieved National Cholesterol Education Program-ATP III targets for low-density lipoprotein cholesterol (LDL-C). We measured fasting lipid profile, apolipoproteins, cholesteryl ester transfer protein (CETP) activity, paraoxonase 1 (PON1) activity, small dense LDL apoB (sdLDL-apoB), oxidized LDL (oxLDL), glycated apoB (glyc-apoB), lipoprotein phospholipase A2 (Lp-PLA2), lysophosphatidyl choline (lyso-PC), macrophage chemoattractant protein (MCP1), serum amyloid A (SAA) and myeloperoxidase (MPO). We also examined the capacity of HDL to protect LDL from in vitro oxidation and the percentage cholesterol efflux mediated by apoB depleted serum. ERN/LRP was associated with an 18% increase in HDL-C levels compared to placebo (1.55 versus 1.31 mmol/L, P<0.0001). There were significant reductions in total cholesterol, triglycerides, LDL cholesterol, total serum apoB, lipoprotein (a), CETP activity, oxLDL, Lp-PLA2, lyso-PC, MCP1, and SAA, but no significant changes in glyc-apoB or sdLDL-apoB concentration. There was a modest increase in cholesterol efflux function of HDL (19.5%, P=0.045), but no change in the antioxidant capacity of HDL in vitro or PON1 activity. CONCLUSIONS:  ERN/LRP reduces LDL-associated mediators of vascular inflammation, but has varied effects on HDL functionality and LDL quality, which may counter its HDL-C-raising effect. CLINICAL TRIAL REGISTRATION:  URL: Unique identifier: NCT01054508.



Derosa, G, et al. (2015), ‘Berberis aristata/Silybum marianum fixed combination (Berberol(®)) effects on lipid profile in dyslipidemic patients intolerant to statins at high dosages: a randomized, placebo-controlled, clinical trial.’, Phytomedicine, 22 (2), 231-37. PubMed: 25765827
Harris, JI, et al. (2004), ‘Statin treatment alters serum n-3 and n-6 fatty acids in hypercholesterolemic patients.’, Prostaglandins Leukot Essent Fatty Acids, 71 (4), 263-69. PubMed: 15310527
Issa, OM, et al. (2018), ‘Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).’, Am Heart J, 195 70-77. PubMed: 29224648
Ooi, EM, et al. (2015), ‘Effects of extended-release niacin on the postprandial metabolism of Lp(a) and ApoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus.’, Arterioscler Thromb Vasc Biol, 35 (12), 2686-93. PubMed: 26515419
Pang, J, et al. (2016), ‘Effect of niacin on triglyceride-rich lipoprotein apolipoprotein B-48 kinetics in statin-treated patients with type 2 diabetes.’, Diabetes Obes Metab, 18 (4), 384-91. PubMed: 26679079
Qin, XF, et al. (2015), ‘Effects of vitamin D on plasma lipid profiles in statin-treated patients with hypercholesterolemia: A randomized placebo-controlled trial.’, Clin Nutr, 34 (2), 201-6. PubMed: 24844869
Rizvi, K., J. P. Hampson, and J. N. Harvey (2002), ‘Do lipid-lowering drugs cause erectile dysfunction? A systematic review’, Fam Pract, 19 (1), 95-98. PubMed: 11818357
Schooling, C. M., et al. (2013), ‘The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials’, BMC Med, 11 57. PubMed: 23448151
Shewmon, DA and JM Craig (2010), ‘Creatine supplementation prevents statin-induced muscle toxicity.’, Ann Intern Med, 153 (10), 690-92. PubMed: 21079234
Silva, M, et al. (2007), ‘Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy.’, Clin Ther, 29 (2), 253-60. PubMed: 17472818
Skarlovnik, A, et al. (2014), ‘Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study.’, Med Sci Monit, 20 2183-88. PubMed: 25375075
Yadav, R, et al. (2015), ‘Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients.’, J Am Heart Assoc, 4 (9), e001508. PubMed: 26374297