BackgroundSoluble Receptor for Advanced Glycation End Products (sRAGE) may be considered a marker inversely related to inflammation and its participation has been established in patients with advanced atherosclerotic vascular diseases. However, it is still unknown whether sRAGE reduction could be early metabolic change in the first stage of hypertension and initial hypertension-associated cardiac damage. We sought to determine the sRAGE values in otherwise healthy, untreated and recently diagnosed mild hypertensives and evaluate their association with blood pressure (BP) values, metabolic parameters, and with subclinical initial signs of cardiac target organ damage (TOD).MethodssRAGE were measured in 100 hypertensive and 100 normotensive subjects matched for age, gender and body mass index (BMI), submitted to a clinic visit and both ambulatory BP monitoring and echocardiography to determine the presence of initial cardiac TOD (presence of signs of left ventricular hypertrophy: left ventricular mass indexed for height2.7 (LVMi) > 48 g/m2.7 for men and > 44 g/m2.7 for women and/or increased left atrial volume 4-chamber indexed for body surface area (LAVi) > 34 ml/m2).ResultssRAGE levels were similar between hypertensive and normotensive subjects and were not significantly correlated with office and 24-h BPs values. However, when subgrouping the hypertensive patients in Hyp-TOD and Hyp-withoutTOD, sRAGE was found to be different among the three groups (p = 0.030), being lower in the Hyp-TOD group than the values of both Hyp-withoutTOD (p = 0.038) and normotensives (p = 0.038). In hypertensive patients sRAGE was negatively related with both LVMi (r = − 0.239, p = 0.034) and LAVi (r = − 0.315, p = 0.005) and was independently related to cardiac TOD also in multivariable analysis.ConclusionsIn this population of mild hypertensives, low circulating sRAGE may be a very early marker of initial TOD, suggesting the possible participation of oxidative stress in initial cardiac changes in human hypertension.Electronic supplementary materialThe online version of this article (10.1186/s12933-019-0821-5) contains supplementary material, which is available to authorized users.
Aim Dyslipidemia is recognized as one of the major risk factors for cardiovascular diseases. This retrospective observational study was aimed to assess the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in dyslipidemic patients with a lipid profile not well controlled by maximally tolerated statin therapy or intolerant to these lipid-lowering drugs. We enrolled 151 patients, of whom, 119 were taking evolocumab and 32 alirocumab.Results Total cholesterol significantly decreased progressively until the fourth year; after 4 years there was a significant reduction (S125.5 mg/dl, S51.5%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year and P < 0.05 vs 2 years) and S2.8 mg/dl (S2.3%) compared with the third year. Lowdensity lipoprotein-cholesterol (LDL-C) also decreased significantly until the fourth year. After 3 years, there was a significant reduction (S117.8 mg/dl, S71.5%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year) and S13.9 mg/dl (S22.8%) compared with the second year; after 4 years there was a significant reduction (S121.4 mg/dl, S73.7%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year and P < 0.05 vs 2 years) and S3.6 mg/dl (S7.7%) compared with the third year. Highdensity lipoprotein-cholesterol increased significantly only during the fourth year of detection. After 3 years, there was a nonsignificant increase (4.9 mg/dl, 10.0%, P U 0.061 vs baseline) and 1.6 mg/dl (3.1%) compared with the second year; after 4 years, there was a significant increase (5.2 mg/dl, 10.6%, P < 0.05 vs baseline) and 0.3 mg/dl (0.6%) compared with the third year. The value of Tg was significantly reduced progressively until the second year and then stabilized in the third and fourth years. After 3 years, the value of Tg stabilized (S48.6 mg/dl, S32.4%, P < 0.01 vs baseline, and P < 0.05 vs 1 year) and S4.8 mg/dl (S4.5%) compared with the second year; after 4 years (S46.4 mg/dl, S31.0%, P < 0.01 vs baseline, and P < 0.05 vs 1 year) there was a slight and nonsignificant increase of 2.2 mg/dl (2.2%) compared with the third year. Regarding adverse events, both drugs were well tolerated.Conclusions We showed that PCSK9 inhibitors are well tolerated and provide long-term significant LDL-C lowering in individuals with hyperlipidemia.
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