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BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively decrease low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events in patients at very high cardiovascular risk. Recent short-term studies suggest a partially LDL-C independent beneficial effect of PCSK9 inhibitor (PCSK9i) therapy on endothelial function and arterial stiffness, whereas it is unknown if this effect persists and what the effect is on microcirculation. OBJECTIVE: To investigate the effects of PCSK9i therapy on vascular parameters beyond its lipid lowering effect. METHODS: In this prospective trial, 32 patients at very high cardiovascular risk and indication for PCSK9i therapy were included. Measurements were performed at baseline and after 6 months of PCSK9i treatment. Endothelial function was assessed as flow-mediated dilation (FMD). Arterial stiffness was measured as pulse wave velocity (PWV) and aortic augmentation index (AIx). Peripheral tissue oxygenation (StO2) as a marker of microvascular function was assessed at the distal extremities using near-infrared spectroscopy camera. RESULTS: Six months of PCSK9i therapy decreased LDL-C levels from 141 ± 54 to 60 ± 30 mg/dl (-56 ± 21 %, p < 0.001), FMD significantly increased from 5.4 ± 1.7 % to 6.4 ± 1.9 % (+19 ± 10 %, p < 0.001), PWV decreased in male patients significantly from 8.9 ± 2.1 to 7.9 ± 1.5 m/s (-12 ± 9 %, p = 0.025). AIx decreased from 27.1 ± 10.4 % to 23.0 ± 9.7 % (-16 ± 14 %, p < 0.001), StO2 significantly increased from 67 ± 12 % to 71 ± 11 % (+7 ± 6 %, p = 0.012). Brachial and aortic blood pressure showed no significant changes after six months. There was no correlation between LDL-C reduction and changes in vascular parameters. CONCLUSIONS: Chronic PCSK9i therapy is associated with sustained improvements in endothelial function, arterial stiffness, and microvascular function independent from lipid lowering.

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PURPOSE: to assess the impact of preventive counseling with focus on diet modification on lipid and metabolic parameters in patients with high / very high cardiovascular (CV) risk who visited Health centers. MATERIALS AND METHODS: This was a prospective randomized controlled study of patients aged 40 to 65 years with high/very high CV risk (≥5% according to the Systematic Coronary Risk Evaluation scale [SCORE]) and any 2 criteria for metabolic syndrome. Patients were 1:1 randomized into 2 groups. The intervention group (n=50) received comprehensive preventive counseling with focus on diet modification followed by remote preventive counseling by phone every two weeks for the first 3 months after enrollment (a total of 6 sessions). The control group (n=50) received usual care in Health centers which also included basic preventive counseling. RESULTS: A total of 100 patients (women 82%, age 59.74±4.66 years) were randomized. At baseline 81% of patients had high and 19% - very high CV risk. The groups were well balanced according to demographic and clinical features. At 1 year of follow-up patients from the intervention group experienced significant improvement of metabolic parameters compared with controls: their diastolic blood pressure (BP) decreased by 5.62±7.7 mm Hg, total and low-density lipoprotein cholesterol (TC and LDL-C) - by 0.5±0.83 and 0.46±0.62 mmol/l, respectively. Both groups experienced statistically and clinically significant decreases in systolic BP (intervention, - 17.76±16.2 mm Hg, control, - 13.44±15.6 mm Hg; both groups p.

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BACKGROUND: Dyslipidemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. Current South African guidelines recommend titrating lipid-lowering therapy (LLT) to low-density lipoprotein cholesterol (LDL-C) targets stratified by cardiovascular risk. The LDL-C goal for very high-risk patients is <1.8 mmol/L. In international studies, approximately 30% of patients do not achieve this goal despite receiving maximally tolerated statin doses. There is, however, a paucity of data on LDL-C goal achievement in very high-risk South African patients receiving maximal statin doses. OBJECTIVE: The goal of the research it to assess LDL-C goal achievement in, and clinical characteristics of, very high cardiovascular risk dyslipidemic patients receiving maximal tolerated statin doses with or without ezetimibe. METHODS: This is an observational, cross-sectional South African registry study that plans to include up to 30 sites and 500 study participants. Adult patients with very high cardiovascular risk status receiving stable, maximally tolerated statin doses (with or without ezetimibe) will be eligible for inclusion. RESULTS: Funding has been awarded and enrollment began on November 15, 2017, and was completed on April 13, 2018, with 507 participants. Database lock was done on June 21, 2018. The statistical analysis has commenced and we expect the final clinical study report to be completed by October 2018. CONCLUSIONS: This study will document the adequacy of LLT in those at highest risk and will thus fill an important data gap in South Africa. This data may be useful in assessing the need for novel LLTs like proprotein convertase subtilisin/kexin 9 inhibitors that substantially lower cholesterol levels in addition to optimal statin therapy. REGISTERED REPORT IDENTIFIER: RR1-10.2196/9248.