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Elevated platelet P-selectin expression and platelet activation in high risk patients with uncontrolled severe hypertension

  • Richard A. Preston
    Correspondence
    Corresponding author at: Division of Clinical Pharmacology, 1500 NW 12th Avenue, 15th Floor West Tower, Miami, FL 33136, United States. Tel.: +1 305 243 6795; fax: +1 305 243 5974.
    Affiliations
    Division of Clinical Pharmacology Clinical Research Center, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, United States
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  • James O. Coffey
    Affiliations
    Division of Clinical Pharmacology Clinical Research Center, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, United States
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  • Barry J. Materson
    Affiliations
    Division of Clinical Pharmacology Clinical Research Center, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, United States
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  • Marlies Ledford
    Affiliations
    Special Coagulation Laboratory, Department of Pathology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, United States
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  • Alberto B. Alonso
    Affiliations
    Division of Clinical Pharmacology Clinical Research Center, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, United States
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      Abstract

      Background

      Uncontrolled severe hypertension is associated with alarming rates of cardiovascular events but the mechanisms of vascular injury are not well understood. Recent investigative interest has focused on platelet activation and platelet P-selectin (CD62P) as direct mediators of vascular inflammation and injury. We investigated the association of extreme blood pressure (BP) elevation with platelet P-selectin and fibrinolytic markers in high risk patients with severe hypertension.

      Methods

      Cross-sectional comparison of platelet CD62, tissue plasminogen activator antigen (tPA), and plasminogen activator inhibitor-1 activity (PAI-1) among 3 BP groups: untreated severely hypertensive patients (SHT; n = 18), untreated mildly hypertensive patients (MHT; n = 19), and normotensive controls (NT; n = 16).

      Results

      Platelet CD62 was greatest in SHT (p = 0.00008) and showed a strong correlation with both systolic (p = 0.0002, r = 0.52) and diastolic (p = 0.0003, r = 0.52) BP. tPA was greater in SHT than MHT or NT (ANOVA; p = 0.02) and correlated with diastolic BP but not SBP. PAI-1 did not correlate with either SBP or DBP but was related to body mass index, diabetes, and dyslipidemia.

      Conclusions

      Platelet CD62 demonstrated a strong and graded association with both systolic and diastolic BP that persisted in the presence of multiple concomitant risk factors. The association of BP with CD62P was stronger than with either PAI-1 or tPA-Ag. Platelet activation and platelet CD62 increase in a BP-dependent manner and this relationship persists at extreme levels of BP. Platelet activation and platelet CD62 may participate in the accelerated target organ injury observed in high risk patients with severe hypertension.

      Keywords

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      References

        • Chobanian A.V.
        • Bakris G.L.
        • Black H.R.
        • et al.
        Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute. National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
        Hypertension. 2003; 42: 1206-1252
        • Veterans Administration Cooperative Study Group on Antihypertensive Agents
        Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressure averaging 115–129 mmHg.
        JAMA. 1967; 202: 116-122
        • Preston R.A.
        • Baltodano N.M.
        • Cienki J.
        • Materson B.J.
        Clinical presentation and management of patients with uncontrolled, severe hypertension: results from a public teaching hospital.
        J Hum Hypertens. 1999; 13: 249-255
        • Preston R.A.
        • Ledford M.R.
        • Materson B.J.
        • et al.
        Effects of severe, uncontrolled hypertension on endothelial activation: sVCAM-1, sICAM-1, and vWF.
        J Hypertens. 2002; 20: 871-877
        • Blann A.D.
        • Nadar S.
        • Lip G.Y.
        Pharmacological modulation of platelet function in hypertension.
        Hypertension. 2003; 42: 1-7
        • Lip G.Y.
        • Blann A.D.
        Does hypertension confer a prothrombotic state? Virchow's triad revisited.
        Circulation. 2000; 101: 218-220
        • Wagner D.D.
        New links between inflammation and thrombosis.
        Arterioscler Thromb Vasc Biol. 2005; 25: 1321-1324
        • Henn V.
        • Slupsky J.R.
        • Grafe M.
        • et al.
        CD40 ligand on activated platelets triggers and inflammatory reaction of endothelial cells.
        Nature. 1998; 391: 591-594
        • Koyama H.
        • Takaaki M.
        • Fukomoto S.
        • et al.
        Platelet P-selectin expression is associated with atherosclerotic wall thickness in carotid artery in humans.
        Circulation. 2003; 108: 524-529
        • Stumpf C.
        • John S.
        • Jukic J.
        • et al.
        Enhanced levels of platelet P-selectin and circulating cytokines in young patients with mild arterial hypertension.
        J Hypertens. 2005; : 995-1000
        • Minuz P.
        • Patrignani P.
        • Gaino S.
        • et al.
        Determinants of platelet activation in human essential hypertension.
        Hypertension. 2004; 43: 64-70
        • Camilletti A.
        • Moretti N.
        • Giacchetti G.
        • et al.
        Decreased nitric oxide levels and increased calcium content in platelets of hypertensive patients.
        Am J Hypertens. 2001; 14: 382-386
        • De Taeye B.
        • Smith L.H.
        • Vaughan D.E.
        Plasminogen activator-1: a common denominator in obesity, diabetes, and cardiovascular disease.
        Curr Opin Pharmacol. 2005; 5: 149-154
        • Poli K.A.
        • Tofler G.H.
        • Larson M.G.
        • et al.
        Association of blood pressure with fibrinolytic potential in the Framingham offspring population.
        Circulation. 2000; 101: 264-269
        • Eliasson M.
        • Jansson J.H.
        • Nilsson P.
        • Asplund K.
        Increased levels of tissue plasminogen activator antigen in essential hypertension. A population-based study in Sweden.
        J Hypertens. 1997; 15: 349-356
        • Held C.
        • Hjemdahl P.
        • Rehnqvist N.
        • et al.
        Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm.
        Circulation. 1997; 95: 2380-2386
        • Thogersen A.M.
        • Jansson J.H.
        • Boman K.
        • et al.
        High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor.
        Circulation. 1998; 98: 2241-2247
        • Meade T.W.
        • Ruddock V.
        • Stirling Y.
        • Chakrabarti R.
        • Miller G.J.
        Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study.
        Lancet. 1993; 342: 1076-1079
        • Ridker P.M.
        • Vaughan D.E.
        • Stampfer M.J.
        • Manson J.E.
        • Hennekens C.H.
        Endogenous tissue-type plasminogen activator and risk of myocardial infarction.
        Lancet. 1993; 341: 1165-1168
        • Brown N.J.
        • Nakamura S.
        • Ma L.
        • et al.
        Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo.
        Kidney Int. 2000; 58: 1219-1227
        • Kaikita K.
        • Fogo A.B.
        • Ma L.
        • et al.
        Plasminogen activator inhibitor-1 deficiency prevents hypertension and vascular fibrosis in response to long-term nitric oxide synthase inhibition.
        Circulation. 2001; 104: 839-851
        • Srikumar N.
        • Brown N.
        • Hopkins P.
        • et al.
        PAI-1 in human hypertension: relation to hypertensive groups.
        Am J Hypertens. 2002; 15: 683-690
        • Lemne C.
        • De Faire U.
        Elevation of plasminogen activator inhibitor 1 in borderline hypertension is linked to concomitant metabolic disturbances.
        Eur J Clin Invest. 1996; 26: 692-697
        • Bastard J.P.
        • Pieroni L.
        • Hainque B.
        Relationship between plasma plasminogen activator inhibitor 1 and insulin resistance.
        Diab/Metab Res Rev. 2000; 16: 192-201
        • Nordt T.K.
        • Schneider D.J.
        • Sobel B.E.
        Augmentation of the synthesis of plasminogen activator inhibitor type-1 by precursors of insulin. A potential risk factor for vascular disease.
        Circulation. 1994; 89: 321-330
        • Kruszynska Y.T.
        • Yu J.G.
        • Olefsky J.M.
        • Sobel B.E.
        Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects.
        Diabetes. 2000; 49: 633-639
        • Vague P.
        • Juhan-Vague I.
        • Chabert V.
        • Alessi M.C.
        • Atlan C.
        Fat distribution and plasminogen activator inhibitor activity in nondiabetic obese women.
        Metabolism. 1989; 38: 913-915
        • McGill J.B.
        • Scneider D.J.
        • Arfken C.L.
        • Lucore C.L.
        • Sobel E.
        Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients.
        Diabetes. 1994; 42: 104-109
        • Jain S.K.
        • Nagi D.K.
        • Slavin B.M.
        • Lumb P.J.
        • Yudkin J.S.
        Insulin therapy in type 2 diabetic subjects suppresses plasminogen activator inhibitor (PAI-1) activity and proinsulin-like molecules independently of glycaemic control.
        Diabet Med. 1993; 10: 27-32
        • Fogari R.
        • Zoppi A.
        • Preti P.
        • et al.
        Differential effects of ACE-inhibition and angiotensin II antagonism on fibrinolysis and insulin sensitivity in hypertensive postmenopausal women.
        Am J Hypertens. 2001; 14: 921-926
        • Jeng J.R.
        • Sheu W.H.
        • Jeng C.Y.
        • Huang S.H.
        • Shieh S.M.
        Impaired fibrinolysis and insulin resistance in patients with hypertension.
        Am J Hypertens. 1996; 9: 484-490
        • Koh K.K.
        • Cardillo C.
        • Bui M.N.
        • et al.
        Vascular effects of estrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women.
        Circulation. 1999; 99: 354-360
        • Newby D.E.
        • Wright R.A.
        • Labinjoh C.
        • et al.
        Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking: a mechanism for arterial thrombosis and myocardial infarction.
        Circulation. 1999; 99: 1411-1415