Research Article| Volume 89, P52-57, July 2016

Observational and mechanistic links between C-reactive protein and blood pressure in elderly women


      • A novel approach combining epidemiological and in-vitro analyses is used to study the influence of C-reactive protein on cardiovascular health in elderly women.
      • The serum level of C-reactive protein is associated with blood pressure in elderly women.
      • C-reactive protein in elderly women limits the proliferative capacity of endothelial cells.
      • C-reactive protein in elderly women reduces the angiogenic potential of endothelial cells.


      It is hypothesized that chronic systemic inflammation contributes to the age-related decline in cardiovascular function. The aim of the present study was to combine an assessment of the relationship between the serum level of C-reactive protein (CRP) and systolic and diastolic blood pressure in 108 elderly women (65 and 70 years) with an in-vitro exploration of the effects of CRP on the proliferative and angiogenic potential of endothelial cells exposed to serum in elderly women. Based on the median CRP level in our population, LowCRP (CRP < 1.3 mg/L) and HighCRP (>1.3 mg/L) groups were identified. Body mass index, waist circumference, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher in the HighCRP group than in the LowCRP group (p < 0.05). The influence of CRP on SBP and DBP remained significant after adjustments for BMI and use of antihypertensive medication (p < 0.05). When adjusting for waist circumference the observed influence of CRP on SPB was attenuated (p = 0.062). We next evaluated the ability to form capillary tubes (angiogenesis assay) and the proliferation rate of endothelial cells exposed to the sera of elderly women. Increased serum CRP levels were associated with an increased doubling time of endothelial cells (R2 = 0.39; p < 0.05) and decreased capillary tube length (R2 = 0.30; p < 0.05), indicating a reduction in the proliferation rate of endothelial cells and angiogenic potential. In conclusion, chronic inflammation influences blood pressure in elderly women and compromises endothelial cell function, thus contributing to the age-related decline in vascular health.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Maturitas
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Danesh J.
        • Wheeler J.G.
        • Hirschfield G.M.
        • Eda S.
        • Eiriksdottir G.
        • Rumley A.
        • Lowe G.D.
        • Pepys M.B.
        • Gudnason V.
        C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease.
        N. Engl. J. Med. 2004; 350: 1387-1397
        • Cesari M.
        • Penninx B.W.
        • Newman A.B.
        • Kritchevsky S.B.
        • Nicklas B.J.
        • Sutton-Tyrrell K.
        • Tracy R.P.
        • Rubin S.M.
        • Harris T.B.
        • Pahor M.
        Inflammatory markers and cardiovascular disease (The health, aging and body composition [Health ABC] study).
        Am. J. Cardiol. 2003; 92: 522-528
        • Pearson T.A.
        • Mensah G.A.
        • Alexander R.W.
        • Anderson J.L.
        • Cannon 3rd., R.O.
        • Criqui M.
        • Fadl Y.Y.
        • Fortmann S.P.
        • Hong Y.
        • Myers G.L.
        • Rifai N.
        • Smith Jr., S.C.
        • Taubert K.
        • Tracy R.P.
        • Vinicor F.
        C. Centers for Disease, Prevention, A. American Heart, Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association.
        Circulation. 2003; 107: 499-511
        • Blake G.J.
        • Ridker P.M.
        Inflammatory bio-markers and cardiovascular risk prediction.
        J. Intern. Med. 2002; 252: 283-294
        • Wang T.J.
        • Gona P.
        • Larson M.G.
        • Levy D.
        • Benjamin E.J.
        • Tofler G.H.
        • Jacques P.F.
        • Meigs J.B.
        • Rifai N.
        • Selhub J.
        • Robins S.J.
        • Newton-Cheh C.
        • Vasan R.S.
        Multiple biomarkers and the risk of incident hypertension.
        Hypertension. 2007; 49: 432-438
        • Talikoti P.
        • Bobby Z.
        • Hamide A.
        Hyperhomocysteinemia, insulin resistance and high HS- CRP levels in prehypertension.
        J Clin Diagn Res. 2014; 8: CC07-CC09
        • Lakoski S.G.
        • Cushman M.
        • Palmas W.
        • Blumenthal R.
        • D'Agostino, Jr., R.B.
        • Herrington D.M.
        The relationship between blood pressure and C-reactive protein in the Multi-Ethnic Study of Atherosclerosis (MESA).
        J. Am. Coll. Cardiol. 2005; 46: 1869-1874
        • Sesso H.D.
        • Buring J.E.
        • Rifai N.
        • Blake G.J.
        • Gaziano J.M.
        • Ridker P.M.
        C-reactive protein and the risk of developing hypertension.
        JAMA. 2003; 290: 2945-2951
        • Sesso H.D.
        • Wang L.
        • Buring J.E.
        • Ridker P.M.
        • Gaziano J.M.
        Comparison of interleukin-6 and C-reactive protein for the risk of developing hypertension in women.
        Hypertension. 2007; 49: 304-310
        • Fujii M.
        • Ohnishi H.
        • Saitoh S.
        • Akasaka H.
        • Miura T.
        • Mori M.
        The combination of abdominal obesity and high-sensitivity C-reactive protein predicts new-onset hypertension in the general Japanese population: the Tanno-Sobetsu study.
        Hypertens. Res. 2015; 38: 426-432
        • Higashi Y.
        • Kihara Y.
        • Noma K.
        Endothelial dysfunction and hypertension in aging.
        Hypertens. Res. 2012; 35: 1039-1047
        • Liu C.
        • Wang S.
        • Deb A.
        • Nath K.A.
        • Katusic Z.S.
        • McConnell J.P.
        • Caplice N.M.
        Proapoptotic, antimigratory, antiproliferative, and antiangiogenic effects of commercial C-reactive protein on various human endothelial cell types in vitro: implications of contaminating presence of sodium azide in commercial preparation.
        Circ. Res. 2005; 97: 135-143
        • Åstrand P.-O.
        • Rodahl K.
        • Dahl H.A.
        • Strømme S.B.
        Textbook of Work Physiology: Physiological Bases of Exercise.
        Human Kinetics Champaign, IL2003
        • Barro M.
        • Carnac G.
        • Flavier S.
        • Mercier J.
        • Vassetzky Y.
        • Laoudj-Chenivesse D.
        Myoblasts from affected and non-affected FSHD muscles exhibit morphological differentiation defects.
        J. Cell. Mol. Med. 2010; 14: 275-289
        • Verma S.
        • Kuliszewski M.A.
        • Li S.H.
        • Szmitko P.E.
        • Zucco L.
        • Wang C.H.
        • Badiwala M.V.
        • Mickle D.A.
        • Weisel R.D.
        • Fedak P.W.
        • Stewart D.J.
        • Kutryk M.J.
        C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: further evidence of a mechanistic link between C-reactive protein and cardiovascular disease.
        Circulation. 2004; 109: 2058-2067
        • Chuang S.Y.
        • Hsu P.F.
        • Chang H.Y.
        • Bai C.H.
        • Yeh W.T.
        • Pan H.W.
        C-reactive protein predicts systolic blood pressure and pulse pressure but not diastolic blood pressure: the cardiovascular disease risk factors two-township study.
        Am. J. Hypertens. 2013; 26: 657-664
        • Bastard J.P.
        • Jardel C.
        • Delattre J.
        • Hainque B.
        • Bruckert E.
        • Oberlin F.
        Evidence for a link between adipose tissue interleukin-6 content and serum C-reactive protein concentrations in obese subjects.
        Circulation. 1999; 99: 2221-2222
        • Poirier P.
        • Giles T.D.
        • Bray G.A.
        • Hong Y.
        • Stern J.S.
        • Pi-Sunyer F.X.
        • Eckel R.H.
        A. American heart, P.A. obesity committee of the council on nutrition, metabolism, obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 american heart association scientific statement on obesity and heart disease from the obesity committee of the council on nutrition, physical activity, and metabolism.
        Circulation. 2006; 113: 898-918
        • Simonds S.E.
        • Pryor J.T.
        • Ravussin E.
        • Greenway F.L.
        • Dileone R.
        • Allen A.M.
        • Bassi J.
        • Elmquist J.K.
        • Keogh J.M.
        • Henning E.
        • Myers Jr., M.G.
        • Licinio J.
        • Brown R.D.
        • Enriori P.J.
        • O'Rahilly S.
        • Sternson S.M.
        • Grove K.L.
        • Spanswick D.C.
        • Farooqi I.S.
        • Cowley M.A.
        Leptin mediates the increase in blood pressure associated with obesity.
        Cell. 2014; 159: 1404-1416
        • Poirier P.
        • Lemieux I.
        • Mauriege P.
        • Dewailly E.
        • Blanchet C.
        • Bergeron J.
        • Despres J.P.
        Impact of waist circumference on the relationship between blood pressure and insulin: the Quebec Health Survey.
        Hypertension. 2005; 45: 363-367
        • Alberti K.G.
        • Zimmet P.
        • Shaw J.
        The metabolic syndrome–a new worldwide definition.
        Lancet. 2005; 366: 1059-1062
        • Funahashi T.
        • Matsuzawa Y.
        Metabolic syndrome: clinical concept and molecular basis.
        Ann. Med. 2007; 39: 482-494
        • Hall J.E.
        • do Carmo J.M.
        • da Silva A.A.
        • Wang Z.
        • Hall M.E.
        Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms.
        Circ. Res. 2015; 116: 991-1006
        • Ferrucci L.
        • Corsi A.
        • Lauretani F.
        • Bandinelli S.
        • Bartali B.
        • Taub D.D.
        • Guralnik J.M.
        • Longo D.L.
        The origins of age-related proinflammatory state.
        Blood. 2005; 105: 2294-2299
        • Hill J.M.
        • Zalos G.
        • Halcox J.P.
        • Schenke W.H.
        • Waclawiw M.A.
        • Quyyumi A.A.
        • Finkel T.
        Circulating endothelial progenitor cells, vascular function, and cardiovascular risk.
        N. Engl. J. Med. 2003; 348: 593-600
        • Wang Q.
        • Zhu X.
        • Xu Q.
        • Ding X.
        • Chen Y.E.
        • Song Q.
        Effect of C-reactive protein on gene expression in vascular endothelial cells.
        Am. J. Physiol. Heart Circ. Physiol. 2005; 288: H1539-45
        • Pasceri V.
        • Willerson J.T.
        • Yeh E.T.
        Direct proinflammatory effect of C-reactive protein on human endothelial cells.
        Circulation. 2000; 102: 2165-2168
        • Devaraj S.
        • Xu D.Y.
        • Jialal I.
        C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis.
        Circulation. 2003; 107: 398-404
        • Torzewski M.
        • Rist C.
        • Mortensen R.F.
        • Zwaka T.P.
        • Bienek M.
        • Waltenberger J.
        • Koenig W.
        • Schmitz G.
        • Hombach V.
        • Torzewski J.
        C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis.
        Arterioscler. Thromb. Vasc. Biol. 2000; 20: 2094-2099
        • Verma S.
        • Wang C.H.
        • Li S.H.
        • Dumont A.S.
        • Fedak P.W.
        • Badiwala M.V.
        • Dhillon B.
        • Weisel R.D.
        • Li R.K.
        • Mickle D.A.
        • Stewart D.J.
        A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis.
        Circulation. 2002; 106: 913-919
        • Nabata A.
        • Kuroki M.
        • Ueba H.
        • Hashimoto S.
        • Umemoto T.
        • Wada H.
        • Yasu T.
        • Saito M.
        • Momomura S.
        • Kawakami M.
        C-reactive protein induces endothelial cell apoptosis and matrix metalloproteinase-9 production in human mononuclear cells: implications for the destabilization of atherosclerotic plaque.
        Atherosclerosis. 2008; 196: 129-135
        • Chen J.
        • Jin J.
        • Song M.
        • Dong H.
        • Zhao G.
        • Huang L.
        C-reactive protein down-regulates endothelial nitric oxide synthase expression and promotes apoptosis in endothelial progenitor cells through receptor for advanced glycation end-products.
        Gene. 2012; 496: 128-135