Age-related increase of thromboxane B2 and risk of cardiovascular disease in atrial fibrillation

Daniele Pastori, Pasquale Pignatelli, Alessio Farcomeni, Cristina Nocella, Simona Bartimoccia, Roberto Carnevale, Francesco Violi, Daniele Pastori, Pasquale Pignatelli, Alessio Farcomeni, Cristina Nocella, Simona Bartimoccia, Roberto Carnevale, Francesco Violi

Abstract

Aging is strictly associated with an increased incidence of cardiovascular events (CVEs) in the general population. Mechanisms underlying the risk of CVEs are still unclear. Platelet activation contributes to the onset of cardiovascular complications. The incidence of atrial fibrillation (AF) increases with age, and the natural history of AF is often complicated by CVEs. We prospectively investigated the relationship between age, urinary thromboxane (Tx) B2, which reflects platelet activation, and CVEs in 833 AF patients. Median TxB2 level was 120 [66-200] ng/mg of urinary creatinine. At multivariable linear regression analysis, age (B: 0.097, p=0.005) and previous MI/CHD (B: 0.069, p=0.047) were associated with log-TxB2 levels. When we divided our population into age classes (i.e. < 60, 60-69, 70-79, ≥ 80 years), we found a significant difference in TxB2 levels across classes (p=0.005), with a significant elevation at 74.6 years. During a mean follow-up of 40.9 months, 128 CVEs occurred; the rate of CVEs significantly increased with age classes (Log-rank test, p < 0.001). TxB2 levels were higher in patients with, compared to those without, CVEs in patients aged 70-79 (p < 0.001) and ≥ 80 (p = 0.020) years. In conclusion, TxB2 levels enhance by increasing age, suggesting that platelet activation contributes to CVEs in elderly patients with AF.

Keywords: Gerotarget; aging; atrial fibrillation; cardiovascular disease; platelet; thromboxane.

Conflict of interest statement

The authors declare no actual or potential conflicts of interests.

Figures

Figure 1. Excretion of urinary 11-dehydro-TxB 2…
Figure 1. Excretion of urinary 11-dehydro-TxB2 according to age classes
Figure 2. Kaplan-Meier survival curves according to…
Figure 2. Kaplan-Meier survival curves according to age classes

References

    1. Christensen K, Doblhammer G, Rau R, Vaupel JW. Ageing populations: the challenges ahead. Lancet. 2009;374:1196–1208.
    1. FitzGerald GA. Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. Am J Cardiol. 1991;68:11B–15B.
    1. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, stroke in high risk patients. Bmj. 2002;324:71–86.
    1. Dayal S, Wilson KM, Motto DG, Miller FJ, Jr, Chauhan AK, Lentz SR. Hydrogen peroxide promotes aging-related platelet hyperactivation and thrombosis. Circulation. 2013;127:1308–1316.
    1. Mohebali D, Kaplan D, Carlisle M, Supiano MA, Rondina MT. Alterations in platelet function during aging: clinical correlations with thromboinflammatory disease in older adults. Journal of the American Geriatrics Society. 2014;62:529–535.
    1. Reilly IA, FitzGerald GA. Eicosenoid biosynthesis and platelet function with advancing age. Thrombosis research. 1986;41:545–554.
    1. Alessandrini P, Avogaro P, Bittolo Bon G, Patrignani P, Patrono C. Physiologic variables affecting thromboxane B2 production in human whole blood. Thrombosis research. 1985;37:1–8.
    1. Ball J, Carrington MJ, McMurray JJ, Stewart S. Atrial fibrillation: profile and burden of an evolving epidemic in the 21st century. International journal of cardiology. 2013;167:1807–1824.
    1. Soliman EZ, Safford MM, Muntner P, Khodneva Y, Dawood FZ, Zakai NA, Thacker EL, Judd S, Howard VJ, Howard G, Herrington DM, Cushman M. Atrial Fibrillation and the Risk of Myocardial Infarction. JAMA internal medicine. 2013
    1. Pastori D, Pignatelli P, Angelico F, Farcomeni A, Del Ben M, Vicario T, Bucci T, Raparelli V, Cangemi R, Tanzilli G, Lip GY, Violi F. Incidence of myocardial infarction and vascular death in elderly patients with atrial fibrillation taking anticoagulants: relation to atherosclerotic risk factors. Chest. 2015;147:1644–1650.
    1. Catella F, Healy D, Lawson JA, FitzGerald GA. 11-Dehydrothromboxane B2: a quantitative index of thromboxane A2 formation in the human circulation. Proceedings of the National Academy of Sciences of the United States of America. 1986;83:5861–5865.
    1. Pignatelli P, Pulcinelli FM, Lenti L, Gazzaniga PP, Violi F. Hydrogen peroxide is involved in collagen-induced platelet activation. Blood. 1998;91:484–490.
    1. Eikelboom JW, Hankey GJ, Thom J, Bhatt DL, Steg PG, Montalescot G, Johnston SC, Steinhubl SR, Mak KH, Easton JD, Hamm C, Hu T, Fox KA, et al. Incomplete inhibition of thromboxane biosynthesis by acetylsalicylic acid: determinants and effect on cardiovascular risk. Circulation. 2008;118:1705–1712.
    1. Hansen ML, Sorensen R, Clausen MT, Fog-Petersen ML, Raunso J, Gadsboll N, Gislason GH, Folke F, Andersen SS, Schramm TK, Abildstrom SZ, Poulsen HE, Kober L, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Archives of internal medicine. 2010;170:1433–1441.
    1. Santilli F, Mucci L, Davi G. TP receptor activation and inhibition in atherothrombosis: the paradigm of diabetes mellitus. Internal and emergency medicine. 2011;6:203–212.
    1. Pastori D, Pignatelli P, Farcomeni A, Cangemi R, Hiatt WR, Bartimoccia S, Nocella C, Vicario T, Bucci T, Carnevale R, Lip GY, Violi F. Urinary 11-dehydro-thromboxane B2 is associated with cardiovascular events and mortality in patients with atrial fibrillation. American heart journal. 2015;170:490–497. e491.

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