Association of aortic valve sclerosis with thrombin generation in hypertensive patients

Abstract

Aortic valve sclerosis (AVS) may predispose to a prothrombotic state, as AVS is predictor of cardiovascular events in hypertensive populations. Thrombin exerts non-thrombotic effects such as vessel tone regulation, progression of atherosclerosis and stimulation of atrial natriuretic peptide (ANP) secretion. We hypothesized that hypertensive patients with AVS may have a persistently activated thrombin generation. We studied 234 asymptomatic never-treated hypertensive patients (73 of them with AVS). Prothrombin F1 þ 2 (F1 þ 2), as a marker of thrombin generation and fibrin D-dimer, as a marker of thrombus formation, ANP and brain natriuretic peptide (BNP) were measured. Presence of AVS, aortic jet velocity and left ventricular diameter at diastole were determined by echocardiography. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula. F1 þ 2 (median and interquartile range (IQR) ¼ 1.05, 0.87-1.38 nM vs 0.93, 0.72-1.16) and ANP (22, 14-37 pg ml À1 vs 17, 11-25) levels were greater, and glomerular filtration rate values (65 ± 9 ml min À1 /1.73 m 2 vs 68 ± 11) were lower in hypertensive patients with AVS than in those without AVS. F1 þ 2 (odds ratio, 95% CI ¼ 2.94, 1.07-8.6) was independently associated with AVS after being adjusted for age, gender and the variables of cardiorenal functions measured. After 6 months of treatment using valsartan, F1 þ 2 levels remained elevated in hypertensive patients with AVS (1.14, 0.83-1.42 nM vs 1.07, 0.84-1.5, n ¼ 19), but decreased in those without AVS (1.01, 0.85-1.31 vs 0.8, 0.84-1.78, n ¼ 27). Thrombin generation was associated with AVS in untreated hypertensive patients, and this association was persistent after blood-pressure-lowering treatment using valsartan.

Whole-Blood Transcriptome Unveils Altered Immune Response in Acute Myocardial Infarction Patients With Aortic Valve Sclerosis

“…In particular, the association of pathways related to increased platelet activation, aggregation, and blood coagulation with AVSc and worse outcomes would suggest that a (marked) prothrombotic state may be responsible, at least in part, for an increased risk of adverse events. 24 In line with our results, t-PA (tissuetype plasminogen activator), an important player in the homeostasis of coagulation and fibrinolysis, was shown to contribute to AVSc development via cytokine release, leading to increased inflammation and endothelial injury. 25 Observation from our study may have a clinical perspective since aggressive antithrombotic preventive strategies could be implemented to decrease the recurrence of cardiovascular adverse events after AMI in patients with AVSc.…”

Hypertension, aortic sclerosis and the prothrombotic state: understanding the complex interaction

“…There is a new concept of not being simply content with just lowering blood pressure and we must tailor the antihypertensive therapy depending on the individual patient and the cardiovascular risk profile. 17 The paper by Iida et al 3 also reports that treatment with valsartan reduced the levels of prothrombin F1 þ 2 in hypertensive patients consistent with previous data in which the treatment of hypertension led to an improvement in the thrombotic profile. 18 In patients with AVS, the levels of the markers of thrombin generation did not differ from baseline, even after 6 months of treatment.…”

“…In this issue of Journal of Human Hypertension, Iida et al 3 conducted an observational and prospective analysis of hypertensive patients with no history of cardiovascular disease, but where the presence of aortic valve sclerosis (AVS) using echocardiography was identified. These authors then report abnormalities in the levels of prothrombin F1 þ 2 (a marker of thrombin generation) and fibrin D-dimer (a marker of fibrin formation), which were found to be greater in patients with AVS than in patients without this valve problem.…”

Mechanisms of fibrinogen‐induced microvascular dysfunction during cardiovascular disease

“…A strong association between elevated levels of Fg and formation of atherosclerotic plaques has been found (Bennett 2001, Lowe & Rumley 2001. Increased binding of Fg to the vascular endothelium and its leakage into the subendothelial matrix may provide favourable conditions for its conversion to fibrin by thrombin, and its generation, which is increased during hypertension (Iida et al 2008) and diabetes (Cohen et al 2002). Increased levels and/or activity of the plasminogen system have not been observed during a majority of the cardiovascular and cerebrovascular diseases.…”