From lipoprotein apheresis to proprotein convertase subtilisin/kexin type 9 inhibitors: Impact on low-density lipoprotein cholesterol and C-reactive protein levels in cardiovascular disease patients

In this observational study, we compared the effect of lipoprotein apheresis and evolocumab or alirocumab on levels of lipoprotein cholesterol, triglycerides and inflammatory markers (C reactive protein and interleukin 6) in cardiovascular patients (n1\u204449). Patients were monitored during the last year of lipoprotein apheresis followed by six months of treatment with proprotein convertase subtilisin/kexin type 9 inhibitors. The biochemical parameters were determined pre- and post- every apheresis procedure for 12 months and then after one, three and six months of treatment with evolocumab (140mg every two weeks [Q2W]) or alirocumab (75mg or 150mg every two weeks [Q2W]). Lipoprotein apheresis significantly reduced low-density lipoprotein cholesterol levels from 138 32 mg/dl to 4616mg/dl (p<0.001), with an inter-apheresis level of 11426mg/dl. Lipoprotein(a) was also reduced from a median of 42 mg/dl to 17 mg/dl (p < 0.01). Upon anti-proprotein convertase subtilisin/kexin type 9 therapy, low-density lipoprotein cholesterol levels were similar to post-apheresis (59 25, 41 22 and 42 21mg/dl at one, three and six months, respectively) as well as those of lipoprotein(a) (18 mg/dl). However, an opposite effect was observed on high- density lipoprotein cholesterol levels: \u201316.0% from pre- to post-apheresis and \ufe34.0% between pre-apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors. Apheresis significantly reduced high-sensitivity C-reactive pro- tein levels (1.5 1.2 mg/l pre-apheresis to 0.6 0.6 mg/l post-apheresis), while no changes were found upon proprotein convertase subtilisin/kexin type 9 mAbs administration. In conclusion, our study demonstrated that, by switching from lipoprotein apheresis to anti-proprotein convertase subtilisin/kexin type 9 therapies, patients reached similar low-density lipoprotein cholesterol and lipoprotein(a) levels, increased those of high-density lipoprotein cholesterol, and showed no changes on high-sensitivity C-reactive protein

E-Selectin plasma concentration is influenced by glycaemic control in NIDDM patients: Possible role of oxidative stress

Although elevated levels of soluble E-selectin and intercellular cell adhesion molecules-1 (ICAM-1) have been reported in non-insulin-dependent diabetes mellitus (NIDDM), it is not clear by what mechanism this elevation occurs and whether or not it is related to glycaemic control. In this study we analyse: 1) the relation of glycaemic control with the concentrations of E-selectin, vascular cell adhesion molecules-1 (VCAM-1) and ICAM-1 in NIDDM patients; 2) whether metabolic control can affect the oxidative stress (as measured by plasma hydroperoxide concentration and susceptibility of LDL to in vitro oxidation) and hence the adhesion molecule plasma concentrations. Thirty-four (19 males and 15 females) poorly controlled NIDDM patients were studied. All parameters were evaluated at the beginning of the study and after 90 days of dietary and pharmacological treatment. The treatment decreased HbA-1C (p lt 0.001), E-selectin (p lt 0.001), plasma hydroperoxides (p lt 0.003) and the susceptibility of LDL to in vitro oxidation (lag phase) (p lt 0.0001). Before treatment HbA-1C, lag phase and lipid hydroperoxides correlated with E-selectin plasma concentration (r = 0.51, -0.57 and 0.54, respectively, p lt 0.01). There was also a correlation between HbA-1C and lag phase (p lt 0.01) and between HbA-1C and lipid hydroperoxides (p lt 0.01). In addition, the variations of HbA-1C, lag phase and lipid hydroperoxide values correlated with those for E-selectin concentration after 90 days' treatment (r = 0.54, -0.64 and 0.61, respectively, p lt 0.01). In multiple linear correlation analysis, however, the partial correlation coefficients of HbA-1C (basal and variations) with E-selectin concentration (basal and variations) fell to non-significant values (r = 0.12 and 0.25, respectively) when LDL lag phase and plasma hydroperoxides were kept constant. The results indicate that the improvement of metabolic control in NIDDM patients is associated with a decrease of E-selectin plasma levels; they also suggest that glycaemic control per se is not directly implicated in determining E-selectin plasma concentration; glycaemic control could affect E-selectin concentration through its effect on oxidative stress

Cardiovascular risk profile in 38-year and 18-year-old men. Contribution of body fat content and regional fat distribution

OBJECTIVE: To evaluate whether young and middle-age men differ in blood pressure and serum lipid profiles and, if so, to what extent these differences are dependent on total body fat, regional fat distribution, plasma insulin and behavioural variables. SUBJECTS: Random samples of 94 young (18 year-old) and 94 middle-age (38 year-old) healthy men matched for body mass index (BMI). MEASUREMENTS: BMI, total body fat (by bioelectrical impedance), regional fat distribution (by anthropometry), serum lipids, blood pressure, fasting insulin and some behavioural variables. RESULTS: Total body fat was similar in the two groups (mean +/- s.e.: 16.6 +/- 0.5 vs 16.0 +/- 0.6 kg and 20.8 +/- 0.5 vs 20 +/- 0.5%), while waist/hip circumference ratio (WHR) was significantly higher in middle-age as compared to young men (0.96 +/- 0.001 vs 0.92 +/- 0.003, P < 0.0001). The former also had significantly higher serum concentrations of total cholesterol (6.21 +/- 0.13 vs 4.10 +/- 0.10 mmol/l; P < 0.0001). LDL-cholesterol (4.24 +/- 0.11 vs 2.34 +/- 0.10 mmol/l; P < 0.0001), triglycerides 1.40 +/- 0.09 vs 1.02 +/- 0.06 mmol/l; P < 0.01) as well as higher systolic (134.0 +/- 1.6 vs 126.3 +/- 1.4 mmHg; P < 0.0001) and diastolic (86.8 +/- 0.9 vs 82.0 +/- 1.1 mmHg; P < 0.001) blood pressure values. HDL-cholesterol and fasting insulin concentrations were similar in the two groups (1.33 +/- 0.03 vs 1.28 +/- 0.03 mmol/l and 13.7 +/- 0.6 vs 14.7 +/- 0.7 mU/l, respectively). Significant differences in the two groups also were found in daily alcohol consumption (49.6 +/- 5.7 vs 20.0 +/- 3.4 g/day; P < 0.0001), whereas no significant differences were found in smoking and physical activity level. The comparison of subgroups (n = 41) of young and middle-age men matched for both BMI and WHR showed virtually unchanged differences in serum lipids and blood pressure. When age, BMI, WHR, fasting insulin and behavioural variables were included as independent variables in a multiple linear regression analysis in which subjects of the two groups were pooled, age was a significant predictor of total and LDL cholesterol, triglycerides and systolic blood pressure, insulin predicted HDL cholesterol and systolic blood pressure, BMI predicted triglycerides and diastolic blood pressure and WHR was not an independent predictor of any risk factor. CONCLUSIONS: These results indicate that middle-age men have a cardiovascular risk profile less favourable than young men, which is largely independent of differences in total body fat content, regional fat distribution and behavioural variables

Improved Quality of Life after bariatric surgery in morbidly obese patients. Interdisciplinary group of bariatric surgery of Verona (G.I.C.O.V.).

Background. Our aim was to evaluate the changes of health-related Quality of Life (HR-QoL) after bariatric surgery. Patients and methods. 110 patients, who underwent laparoscopic bariatric surgery (N=34 gastric banding; N= 69 Roux-en-Y gastric bypass, N=7 sleeve gastrectomy), were evaluated before surgery and after an average of 36\ub113 months with SF-36 Health Survey. Results. Mean preoperative age and body mass index (BMI) were 43\ub112 years and 45\ub17 kg/m2 respectively. At follow-up, mean BMI was 33\ub16 kg/m2. A significant improvement was observed for all dimensions of SF-36, except for General and Mental Health dimension. Satisfaction was greater in patients with the higher reduction in weight. Only the PF (Physical Functioning) domain (F=6,349, p=0.01) resulted a significant predictor of the weight lost after surgery independently of age, sex and type of surgery. Conclusions. We confirm a beneficial effect of bariatric surgery on HR-QoL. Moreover, we found that PF domain of SF-36 is a significant predictor of weight loss