Long-Term Immunomodulatory Effects of a Mediterranean Diet in Adults at High Risk of Cardiovascular Disease in the PREvención con DIeta MEDiterránea (PREDIMED) Randomized Controlled Trial

Abstract Background Consumption of nuts improves cardio-metabolic risk factors in clinical trials and relates to lower risk of cardiovascular disease (CVD) in prospective observational studies. However, there has not been an adequately powered randomized controlled trial to test if nuts supplementation actually reduces incident CVD. In order to establish the feasibility of such a trial, the current study aimed to assess the acceptability and adherence to long-term nut supplementation amongst individuals at high CVD risk in China. Methods This protocol described a 6-month trial performed in Ningxia Province in China among participants with a history of CVD or older age (female ≥65 years, male ≥60 years) with multiple CVD risk factors. Participants were randomized to control (received non-edible gift), low dose walnut (30 g/d), or high dose walnut (60 g/d) groups in a 1:1:1 ratio. Walnuts were provided at no cost to participants and could be consumed according to personal preferences. Follow-up visits were scheduled at 2 weeks, 3 months and 6 months. The primary outcome was fasting plasma alpha linolenic acid (ALA) levels used as an indicator of walnut consumption. Secondary outcomes included self-reported walnut intake from the 24 h dietary recalls. The target sample size of 210 provided 90% statistical power with two-sided alpha of 0.05 to detect a mean difference of 0.12% (as percent of total fatty acid) in plasma ALA between randomized groups. Results Two hundred and ten participants were recruited and randomized during October 2019. Mean age of participants was 65 years (SD = 7.3), 47% were females, and 94% had a history of CVD at baseline. Across the three study groups, participants had similar baseline demographic and clinical characteristics. Discussion This trial will quantify acceptability and adherence to long-term walnut supplementation in a Chinese population at high risk of CVD. The findings will support the design of a future large trial to test the effect of walnut supplementation for CVD prevention. Trial registration NCT04037943 Protocol version: v3.0 August 14 2019

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Endothelial Dysfunction, Atherosclerosis, and Increase of von Willebrand Factor and Factor VIII: A Randomized Controlled Trial in Swine

Thrombosis and Haemostasis ◽

10.1055/s-0040-1722185 ◽

2021 ◽

Author(s):

Ferdows Atiq ◽

Jens van de Wouw ◽

Oana Sorop ◽

Ilkka Heinonen ◽

Moniek P. M. de Maat ◽

...

Keyword(s):

Cardiovascular Disease ◽

Randomized Controlled Trial ◽

Endothelial Dysfunction ◽

Controlled Trial ◽

Short Term ◽

Randomized Controlled ◽

Von Willebrand ◽

Willebrand Factor

AbstractIt is well known that high von Willebrand factor (VWF) and factor VIII (FVIII) levels are associated with an increased risk of cardiovascular disease. It is still debated whether VWF and FVIII are biomarkers of endothelial dysfunction and atherosclerosis or whether they have a direct causative role. Therefore, we aimed to unravel the pathophysiological pathways of increased VWF and FVIII levels associated with cardiovascular risk factors. First, we performed a randomized controlled trial in 34 Göttingen miniswine. Diabetes mellitus (DM) was induced with streptozotocin and hypercholesterolemia (HC) via a high-fat diet in 18 swine (DM + HC), while 16 healthy swine served as controls. After 5 months of follow-up, FVIII activity (FVIII:C) was significantly higher in DM + HC swine (5.85 IU/mL [5.00–6.81]) compared with controls (4.57 [3.76–5.40], p = 0.010), whereas VWF antigen (VWF:Ag) was similar (respectively 0.34 IU/mL [0.28–0.39] vs. 0.34 [0.31–0.38], p = 0.644). DM + HC swine had no endothelial dysfunction or atherosclerosis during this short-term follow-up. Subsequently, we performed a long-term (15 months) longitudinal cohort study in 10 Landrace–Yorkshire swine, in five of which HC and in five combined DM + HC were induced. VWF:Ag was higher at 15 months compared with 9 months in HC (0.37 [0.32–0.42] vs. 0.27 [0.23–0.40], p = 0.042) and DM + HC (0.33 [0.32–0.37] vs. 0.25 [0.24–0.33], p = 0.042). Both long-term groups had endothelial dysfunction compared with controls and atherosclerosis after 15 months. In conclusion, short-term hyperglycemia and dyslipidemia increase FVIII, independent of VWF. Long-term DM and HC increase VWF via endothelial dysfunction and atherosclerosis. Therefore, VWF seems to be a biomarker for advanced cardiovascular disease.

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