Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels.

The current guidelines following an acute coronary syndrome recommend dual-antiplatelet therapy (DAPT) (aspirin plus a P2Y12 antagonist) alongside lifestyle modifications, including more regular physical activity. It is currently unknown whether regular exercise affects the pharmacology of DAPT. AIM: To explore how exercise-induced improvements in vascular and platelet function affect the efficacy of DAPT, in a cross-sectional study of men with different physical activity levels (training status). METHODS: A total of 42 healthy, normal-weight, middle-aged men were divided into 3 groups: untrained, moderately trained and well-trained. Their platelet reactivity (agonist-induced % aggregation) was investigated in platelet-rich plasma at rest and after inhibition with aspirin and ticagrelor and/or prostacyclin and nitric oxide added to the blood in vitro, and after physiological tests of vascular function; passive movement of the leg, flow-mediated dilation and one-leg knee-extensor exercise. Vascular function of the femoral artery (changes in arterial blood flow) was assessed by ultrasound Doppler. RESULTS: Platelets from the well-trained subjects had lower basal reactivity, a higher sensitivity to the anti-aggregatory effects of prostacyclin and were more potently inhibited by DAPT compared to the untrained subjects. The moderately trained and well-trained subjects had a superior vascular function compared to untrained subjects, and their platelets were more inhibited by the passive movement, flow-mediated dilation and one-leg knee-extensor exercise. DISCUSSION: A habitually active lifestyle leads to an increased platelet sensitivity to pharmacological and physiological platelet inhibitors. We suggest that physical activity habits (training status) should be considered when personalizing and optimizing antithrombotic treatment strategies.

Influence of short term verapamil treatment on glucose metabolism in patients with non-insulin dependent diabetes mellitus.

The effect of a sustained-release verapamil preparation on glucose metabolism was investigated in 10 patients with non-insulin dependent diabetes mellitus. In a single blind cross-over study verapamil 240 mg b.d. for 1 week lowered fasting plasma glucose from a mean value of 11.6 mmol/l to 10.3 mmol.l-1, and the fasting glucose appearance rate was decreased from 1.5 to 1.2 mmol.min-1. The decrease in fasting plasma glucose and glucose appearance rate was not related to the steady state plasma concentration of verapamil, nor-verapamil and the metabolites D.617 and D.620. After oral glucose administration a tendency to lower plasma glucose values was found after verapamil administration. Plasma insulin, C-peptide, total and C-terminal glucagon were not significantly different in the placebo and the verapamil studies, neither in the fasting state nor after glucose. It is concluded that brief verapamil treatment decreases fasting plasma glucose and glucose turn-over in non-insulin dependent diabetics, possibly by inhibition of gluconeogenesis.