Our data indicate a high prevalence of comorbidities in patients with PA. The hypokalemic variant is defined by a higher morbidity than the normokalemic variant regarding some cardiovascular but not cerebrovascular events. Thus, PA should be sought not only in hypokalemic but also in normokalemic hypertensives because high-excess morbidity occurs in both subgroups.

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In a large cohort of patients with PA, markers of disease activity such as plasma aldosterone and serum potassium are independent predictors of a lower GFR. Specific interventions, such as adrenalectomy or spironolactone treatment, are associated with a further decline in GFR.

Strenuous, anaerobic exercise leads to an increase of leukocytes that are mobilized from the marginal pool. We have analyzed in human peripheral blood the effect of exercise on the number of CD14(+)CD16(+) monocytes as determined by two-color immunofluorescence and flow cytometry. We show herein that this type of monocyte responds with a dramatic up to 4.8-fold increase. Mobilization does not occur after 1 min at 100 or 200 W but 1 min at 400 W leads to a twofold increase of the CD14(+)CD16(+) monocytes immediately after exercise. The numbers remain high at 5 min and gradually decrease to reach the initial level at 20 min postexercise. After 20 min of rest, the CD14(+)CD16(+) monocytes can be mobilized again by a second exercise. The CD14(+)CD16(+) monocytes appear to be mobilized from the marginal pool where they preferentially home because of a higher expression of adhesion molecules like CD11d and very late antigen-4. Exercise goes along with an increase of catecholamines, and mobilization of the CD14(+)CD16(+) monocytes can be substantially reduced by treatment of donors with the beta-adrenergic receptor blocker propranolol. Mobilization of CD14(+)CD16(+) monocytes by a catecholamine-dependent mechanism may contribute to the increase of these cells in various clinical conditions.

Interaction of von Willebrand factor (VWF) with platelet glycoprotein Ib (GPIb) and interaction of collagen with GPVI are essential for thrombus formation on ruptured or eroded atherosclerotic plaques (atherothrombosis). GPIb and GPVI signal through Bruton tyrosine kinase (Btk), which can be blocked irreversibly by oral application of ibrutinib, an established therapy for chronic lymphocytic leukemia (CLL) with long-term safety. We found that ibrutinib and the novel Btk inhibitors acalabrutinib and ONO/GS-4059 block GPVI-dependent static platelet aggregation in blood exposed to human plaque homogenate and collagen but not to ADP or arachidonic acid. Moreover, Btk inhibitors prevented platelet thrombus formation on human atherosclerotic plaque homogenate and plaque tissue sections from arterially flowing blood, whereas integrin αβ and VWF-dependent platelet adhesion to collagen, which is important for physiologic hemostasis, was not affected. This plaque-selective platelet inhibition was also observed in CLL patients taking 450 mg of ibrutinib and in volunteers after much lower and intermittent dosing of the drug. We conclude that Btk inhibitors, by targeting GPIb and GPVI signal transduction, suppress platelet thrombus accretion from flowing blood on atherosclerotic plaque but spare hemostatic platelet function. Btk inhibitors hold promise as the first culprit lesion-focused oral antiplatelet drugs and are effective at low doses.