Advertisement

Independent and additive effects of cytokine patterns and the metabolic syndrome on arterial aging in the SardiNIA Study

      Abstract

      Objective

      Metabolic syndrome (MetS) and its components accelerate age-associated increases in arterial stiffness and thickness. We investigated whether specific proinflammatory cytokines contribute to arterial aging, independent of age, sex, MetS, and other traditional CV risk factors.

      Research design and methods

      MetS components (ATP III criteria) and arterial properties were assessed in 6148 subjects, aged 14–102 in Sardinia, Italy. Common carotid artery (CCA) diameter, intima-media thickness (IMT), and aortic pulse wave velocity (PWV), adiponectin, leptin, high-sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein 1 (MCP1), and interleukin 6 (IL6) were measured.

      Results

      While cytokine levels – except for MCP1 – were significantly higher (lower for adiponectin) in MetS than in control subjects, and the increased PWV and CCA IMT with aging were associated with MetS, this association was independent of cytokine levels (p < 0.001 for both PWV and CCA IMT). Specific cytokines, however, were significantly associated with arterial stiffness (higher leptin, p < 0.001, and higher hsCRP, p < 0.001) or thickness (lower adiponectin, p < 0.05, and higher IL6, p < 0.001) – independent of age, sex, MetS and other traditional CV risk factors. The co-occurrence of both MetS and higher cytokines levels was associated with greater increases in arterial stiffness and thickness.

      Conclusion

      While MetS and specific cytokine patterns associated with arterial aging, the increases in arterial stiffness and thickness are greater when both MetS and higher cytokine levels are present, suggesting a possible synergistic effect of MetS and inflammation on the arterial wall.

      Keywords

      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:

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

      References

        • Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III)
        Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults.
        JAMA. 2001; 285: 2486-2497
        • Scuteri A.
        • Najjar S.S.
        • Morrell C.H.
        • Lakatta E.G.
        The metabolic syndrome in older individuals: prevalence and prediction of cardiovascular events: the cardiovascular health study.
        Diabetes Care. 2005; 28: 882-887
        • Scuteri A.
        • Najjar S.S.
        • Muller D.C.
        • et al.
        Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness.
        JACC. 2004; 43: 1388-1395
        • Scuteri A.
        • Najjar S.S.
        • Orru’ M.
        • et al.
        The central arterial burden of the metabolic syndrome is similar in men and women: the SardiNIA study.
        Eur Heart J. 2010; 31: 602-613
        • Grundy S.M.
        Inflammation, hypertension, and the metabolic syndrome.
        JAMA. 2003; 290: 3000-3002
        • Scuteri A.
        • Tesauro M.
        • Rizza S.
        • et al.
        Endothelial function and arterial stiffness in normotensive normoglycemic first-degree relatives of diabetic patients are independent of the metabolic syndrome.
        Nutr Metab Cardiovasc Dis. 2008; 18: 349-356
        • Beltowski J.
        Leptin and atherosclerosis.
        Atherosclerosis. 2006; 189: 47-60
        • Shimada K.
        • Miyazaki T.
        • Daida H.
        Adiponectin and atherosclerotic disease.
        Clin Chim Acta. 2004; 344: 1-12
        • Ridker P.M.
        • Buring J.E.
        • Shih J.
        • Matias M.
        • Hennekens C.H.
        Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women.
        Circulation. 1998; 98: 731-733
        • Barzilay J.I.
        • Abraham L.
        • Heckbert S.R.
        • et al.
        The relation of markers of inflammation to the development of glucose disorders in the elderly: the cardiovascular health study.
        Diabetes. 2001; 50: 2384-2389
        • Pilia G.
        • Chen W.M.
        • Scuteri A.
        • et al.
        Heritability of cardiovascular and personality traits in 6148 Sardinians.
        PLoS Genet. 2006; 2: e132
        • Scuteri A.
        • Najjar S.S.
        • Orru’ M.
        • et al.
        Age-gender-specific awareness, treatment, and control of cardiovascular risk factors and subclinical vascular lesions in a founder population: the SardiNIA Study.
        Nutr Metab Cardiovasc Dis. 2009; 19: 532-534
        • Wellen K.E.
        • Hotamisligil G.S.
        Obesity-induced inflammatory changes in adipose tissue.
        J Clin Invest. 2003; 112: 1785-1788
        • Ouchi N.
        • Ohishi M.
        • Kihara S.
        • et al.
        Hypertension. 2003; 42: 231-234
        • Ouchi N.
        • Kihara S.
        • Arita Y.
        • et al.
        Novel modulator for endothelial adhesion molecules.
        Circulation. 1999; 100: 2473-2476
        • Pischon T.
        • Girman C.J.
        • Hotamisligil G.S.
        • Rifai N.
        • Hu F.B.
        Rimm EB Plasma adiponectin levels and risk of myocardial infarction in men.
        JAMA. 2004; 291: 1730-1737
        • Yasmin
        • McEniery C.M.
        • Wallace S.
        • Mackenzie I.S.
        • Cockcroft J.R.
        • Wilkinson I.B.
        C-reactive protein is associated with arterial stiffness in apparently healthy individuals.
        Arterioscler Thromb Vasc Biol. 2004; 24: 969-974
        • Mahmud A.
        • Freely J.
        Arterial stiffness is related to systemic inflammation in essential hypertension.
        Hypertension. 2005; 46: 1118-1122
        • Mattace-Raso F.U.
        • van der Cammen T.J.M.
        • van der Meer I.M.
        • et al.
        C-reactive protein and arterial stiffness in older adults: the Rotterdam study.
        Atherosclerosis. 2004; 176: 111-116
        • Tsioufls C.
        • Dimitriadis K.
        • Selima M.
        • et al.
        Low-grade inflammation and hypoadiponectinaemia have an additive detrimental effect on aortic stiffness in essential hypertensive patients.
        Eur Heart J. 2007; 28: 1162-1169
        • Singhal A.
        • Farooqi I.S.
        • Cole T.J.
        • et al.
        Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease.
        Circulation. 2002; 106: 1919-1924
        • Pilz S.
        • Horejsi R.
        • Moller R.
        • et al.
        Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin.
        J Clin Endocrinol Metab. 2005; 90: 4792-4796
        • Iglseder B.
        • Mackevics V.
        • Stadlmayer A.
        • Tasch G.
        • Ladurner G.
        • Paulweber B.
        Plasma adiponectin levels and sonographic phenotypes of subclinical carotid artery: data from the SAPHIR study.
        Stroke. 2005; 36: 2577-2582
        • Lo J.
        • Dolan S.E.
        • Kanter J.R.
        • et al.
        Effects of obesity, body composition, and adiponectin on carotid intima-media thickness in healthy women.
        J Clin Endocrinol Metab. 2006; 91: 1677-1682
        • Nilsson P.M.
        • Engstrom G.
        • Hedblad B.
        • et al.
        Plasma adiponectin levels are inversely associated with carotid intima media thickness and markers of insulin resistance in middle-aged men.
        Arterioscler Thromb Vasc Biol. 2006; 26: 2758-2762
        • Patel S.
        • Flyvbjerg A.
        • Koza‘kova‘ M.
        • et al.
        The RISC investigators. Variation in the ADIPOQ gene promoter is associated with carotid intima media thickness independent of plasma adiponectin levels in healthy subjects.
        Eur Heart J. 2008; 29: 386-393
        • Blake G.J.
        • Ridker P.M.
        Novel clinical markers of vascular wall inflammation.
        Circ Res. 2001; 89: 763-771
        • Fried S.K.
        • Bunkin D.A.
        • Greenberg A.S.
        Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid.
        J Clin Endocrinol Metab. 1998; 83: 847-850
        • Scuteri A.
        • Morrell C.H.
        • Najjar S.S.
        • et al.
        Longitudinal paths to the metabolic syndrome: can the incidence of the metabolic syndrome be predicted? The Baltimore longitudinal study of aging.
        J Gerontol: A Biol Sci Med Sci. 2009; 64: 590-598