Safety and Efficacy of Closed-Loop Arbutamine Stress Echocardiography for Detection of Coronary Artery Disease

Bach, David S.; Cohen, Jacob; Fioretti, P.; Ginzton, Leonard E.; Sklar, Joel; Zabalgoitia, Miguel; Crouse, Linda J.

doi:10.1016/s0002-9149(97)00800-x

Cited by 11 publications

(4 citation statements)

References 11 publications

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“…Importantly, statins, which increase the number of LDLRs by inhibiting hydroxymethylglutaryl-CoA reductase, the rate-limiting enzyme of cholesterol synthesis, have been demonstrated to have multiple effects on the metabolism of VLDL, IDL, and LDL. 23,24 Thus, it seemed possible that, depending on the background lipid metabolism present in any individual, one or more of the scenarios described previously might be important in the lowering of LDL-C by inhibition of PCSK9.…”

Section: Discussionmentioning

confidence: 99%

Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans

et al. 2017

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Background Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low density lipoprotein cholesterol (LDL-C) and apolipoprotein B100 (apoB). Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism. In particular, it is not known if inhibition of PCSK9 has any effects on very low density lipoprotein (VLDL) or intermediate density lipoprotein (IDL) metabolism. Inhibition of PCSK9 also results in reductions of plasma Lp(a) levels. The regulation of plasma Lp(a) levels, including the role of LDL receptors (LDLRs) in the clearance of Lp(a), is poorly defined, and there have been no mechanistic studies of the Lp(a) lowering by alirocumab in humans. Methods Eighteen (10F, 8M) participants completed a placebo-controlled, two-period study. They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart. At the end of each period, fractional clearance rates (FCR) and production rates (PR) of apoB and apo(a) were determined. In 10 participants, postprandial triglycerides (TG) and apoB48 levels were measured. Results Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%. The fall in LDL-apoB was due to an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR. The latter was associated with a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL. The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR. Alirocumab had no effects on FCRs or PRs of VLDL-apoB and VLDL-TG, or on postprandial plasma TG or apoB48 concentrations. Conclusions Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs, and decreasing LDL-apoB PR. These results are consistent with increases in LDLRs available to clear IDL and LDL from blood during PCSK9 inhibition. The possible increase in apo(a) FCR during alirocumab treatment suggests that increased LDLRs may also play a role in the reduction of plasma Lp(a). Clinical Trials Registration Clinical trials.gov # NCT01959971

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Section: Discussionmentioning

confidence: 99%

Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans

et al. 2017

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“…Although an elevated risk of diabetes can be predicted in participants with high TG levels, based on the current literature as well as the findings of this study, it cannot be assumed that a reduction in the levels of TGs in a fragmentary manner will lower the risk for the development of diabetes. Statins are effective in lowering LDL-C levels as well as very LDL levels [ 30 ]. However, they have been found to modestly increase the risk of developing diabetes mellitus [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study

et al. 2018

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BackgroundHypertriglyceridemia is known to have an association with increased risks of insulin resistance and diabetes. The aim of this study was to investigate the risk of diabetes mellitus, according to changes in the concentrations of triglycerides, over time.MethodsA total of 15,932 non-diabetic participants (mean age 43.2 years, 68% men) who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital, between January 2010 and December 2014, were recruited. Participants were classified according to their triglyceride concentrations; normal (<150 mg/dL) and abnormal (≥150 mg/dL). According to the triglyceride levels in 2010 and 2012, subjects were divided into four groups: normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal. The risk for incident diabetes was assessed in 2014.ResultsAmong the total subjects, 67.5% belonged to the normal-normal group, 8.6% to the normal-abnormal group, 9.4% to the abnormal-normal group, and 14.5% to the abnormal-abnormal group. A total of 234 subjects (1.5%) were newly diagnosed with diabetes, between 2010 and 2014. Over 4 years, 1%, 1.5%, 2.1%, and 3.0% of the subjects developed diabetes in the normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal groups, respectively. When the risk for incident diabetes was analyzed in the groups, after adjusting the confounding variables, a 1.58-fold increase in the risk of diabetes (95% confidence interval [CI], 1.10 to 2.26) was observed in the participants with persistent hypertriglyceridemia (abnormal-abnormal group). This was attenuated by further adjustments for body mass index (BMI) (hazard ratio, 1.25; 95% CI, 0.86 to 1.80).ConclusionIn this large study population, persistent hypertriglyceridemia, over a period of 2 years, was significantly associated with the risk of incident diabetes, which was attenuated after adjustment for BMI.

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“…Previous randomized trials have demonstrated that the higher the baseline TG value, the greater the therapeutic response. 30,31,32 …”

Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of Fish Oil Versus Fenofibrate, Gemfibrozil, and Atorvastatin on Lowering Triglyceride Levels Among HIV-Infected Patients in Routine Clinical Care

Muñoz

Liu

Delaney

et al. 2013

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective The goal of this study was to compare the effectiveness of fish oil, fenofibrate, gemfibrozil, and atorvastatin on reducing triglyceride (TG) levels among a large cohort of HIV-infected patients in clinical care. Design Retrospective observational cohort study Methods The primary endpoint was absolute change in TG levels measured using the last TG value pre-treatment and the first TG value post-treatment. A pre-post quasi-experimental design was used to estimate the change in TG due to initiating fish oil. Linear regression models examined the comparative effectiveness of treatment with fish oil versus gemfibrozil, fenofibrate, or atorvastatin for TG reduction. Models were adjusted for baseline differences in age, sex, race, CD4+ cell count, diabetes, body mass index, protease inhibitor use, and time between TG measures. Results A total of 493 patients (mean age 46 years; 95% male) were included (46 receiving gemfibrozil, 80 fenofibrate, 291 atorvastatin, 76 fish oil) with a mean baseline TG of 347 mg/dL. New use of fish oil decreased TG (ΔTG -45 mg/dL 95% Confidence interval (CI):-80 to -11) in the pre-post study. Compared with fish oil (reference), fibrates were more effective (ΔTG -66; 95% CI:-120 to -12) in reducing TG levels, whereas atorvastatin was not (ΔTG -39; 95% CI:-86 to 9). Conclusion In HIV-infected patients in routine clinical care, fish oil is less effective than fibrates (but not atorvastatin) at lowering triglyceride values. Fish oil may still represent an attractive alternative for patients with moderately elevated triglycerides particularly among patients who may not want or tolerate fibrates.

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Safety and Efficacy of Closed-Loop Arbutamine Stress Echocardiography for Detection of Coronary Artery Disease

Cited by 11 publications

References 11 publications

Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans

Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans

The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study

Comparative Effectiveness of Fish Oil Versus Fenofibrate, Gemfibrozil, and Atorvastatin on Lowering Triglyceride Levels Among HIV-Infected Patients in Routine Clinical Care

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