Improvement Of Endothelial Function In Patients Research Articles

Endothelial function improvement in patients with familial hypercholesterolemia receiving PCSK-9 inhibitors on top of maximally tolerated lipid lowering therapy

BackgroundTreatment with protein convertase subtilisin kexin type 9 inhibitors (PCSK-9i) reduced cholesterol levels and cardiovascular events in patients with hypercholesterolemia. We assessed changes in lipid profile, oxidation markers and endothelial function in patients with familial hypercholesterolemia (FH) after a 12-week treatment with a PCSK-9i. MethodsPatients with FH starting a treatment with PCSK-9i were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) (Lp(a)), small dense LDL (assessed by LDL score), 11-dehydro-thromboxane (11-TXB2), 8-isoprostaglandin-2alpha (8-iso-PGF2α), flow-mediated dilation (FMD) and reactive hyperaemia index (RHI) were evaluated before starting PCSK-9i treatment and after a 12-week treatment. ResultsTwenty-five subjects were enrolled (52% males, mean age 51.5 years). At the 12-week assessment, we observed a 38% median reduction in TC, 52% in LDL-C, 7% in Lp(a) and 46% in LDL score. In parallel, 11-TXB2 and 8-iso-PGF2α showed a reduction of 18% and 17%, respectively. FMD changed from 4.78% ± 2.27 at baseline to 10.6% ± 5.89 at 12 weeks (p < 0.001), with RHI changing from 2.37 ± 1.23 to 3.76 ± 1.36 (p < 0.001). A multivariate analysis showed that, after adjusting for potential confounders, change in LDL score was an independent predictor of changes in FMD (β = −0.846, p = 0.015) and in 8-iso-PGF2α (β = 0.778, p = 0.012). ConclusionsSmall dense LDL reduction (assessed by LDL score) is related to changes in oxidation markers and endothelial function in patients with FH treated with PCSK-9i.

Predictors of endothelial function improvement in patients with mild hypertriglyceridemia without evidence of coronary artery disease treated with purified eicosapentaenoic acid

Background and aimsEicosapentaenoic acid (EPA) has been reported to reduce cardiovascular risk in patients with hypertriglyceridemia. Although several mechanisms underlying the effects of EPA have been demonstrated, those responsible for its beneficial role in patients with hypertriglyceridemia without evidence of coronary artery disease (CAD) have not been fully elucidated. We sought to clarify the main factors associated with EPA administration that led to improved endothelial function. MethodsForty-seven consecutive patients with mild hypertriglyceridemia (mean age, 59 ± 13 years) without evidence of CAD were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-four patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed between FMD changes and clinical variables. ResultsEPA treatment decreased triglyceride levels (from 224.6 ± 58.8 to 151.8 ± 54.5 mg/dl, p < 0.001) and increased FMD (from 4.21% ± 1.91% to 6.21% ± 2.30%, p < 0.001). Multivariate analysis showed that the change in FMD was associated with the baseline high-density lipoprotein cholesterol (HDL-C) level (β = −0.331, p = 0.027) and the change in EPA/arachidonic acid (AA) ratio (β = 0.301, p = 0.048). ConclusionsEPA treatment improved triglyceride levels and FMD in patients with mild hypertriglyceridemia and without evidence of CAD. The baseline HDL-C level and the change in EPA/AA ratio predicted FMD improvement. The beneficial effects of EPA on triglyceride-rich lipoproteins and vascular endothelium may help improve endothelial function.

Effects of amlodipine and atorvastatin on endothelial vasoactive mediators in patients with metabolic syndrome

Aims: to study the effects of the amlodipine and atorvastatin on the blood levels of vasoactive mediators in patients with metabolic syndrome (MS). Design and methods. There were included 60 patients with MS, hypertension and dyslipidemia who were randomized into three treatment groups: monotherapy with amlodipine, atorvastatin monotherapy and a combination therapy with amlodipine and atorvastatin. Office blood pressure, 24-hour ambulatory blood pressure monitoring, measurements of the NO metabolite levels, endothelin-1, thromboxane B2 (TxB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were performed at baseline and after 24 weeks of the therapy.Results. Amlodipine and atorvastatin in monotherapy or in a combination were associated with the significant improvement of certain studied parameters. Amlodipine treatment significantly decreased TxB2 and 6-keto-PGF1α levels. There was a significant reduction of TxB2, 6-keto-PGF1a levels and increase of NO metabolite in atorvastatin group. Treatment with combination of amlodipine and atorvastatin was characterized by significant decrease of TxB2 and endothelin-1 and increase of NO metabolite.Conclusion. Amlodipine and atorvastatin treatment showed positive effects on the levels of vasoactive mediators thereby leading to the improvementof endothelial function in patients with MS.

Влияние амлодипина и аторвастатина на вазоактивные медиаторы эндотелия у больных с метаболическим синдромом

Aims: to study the effects of the amlodipine and atorvastatin on the blood levels of vasoactive mediators in patients with metabolic syndrome (MS). Design and methods. There were included 60 patients with MS, hypertension and dyslipidemia who were randomized into three treatment groups: monotherapy with amlodipine, atorvastatin monotherapy and a combination therapy with amlodipine and atorvastatin. Office blood pressure, 24-hour ambulatory blood pressure monitoring, measurements of the NO metabolite levels, endothelin-1, thromboxane B2 (TxB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were performed at baseline and after 24 weeks of the therapy.Results. Amlodipine and atorvastatin in monotherapy or in a combination were associated with the significant improvement of certain studied parameters. Amlodipine treatment significantly decreased TxB2 and 6-keto-PGF1α levels. There was a significant reduction of TxB2, 6-keto-PGF1a levels and increase of NO metabolite in atorvastatin group. Treatment with combination of amlodipine and atorvastatin was characterized by significant decrease of TxB2 and endothelin-1 and increase of NO metabolite.Conclusion. Amlodipine and atorvastatin treatment showed positive effects on the levels of vasoactive mediators thereby leading to the improvementof endothelial function in patients with MS.