Semin Thromb Hemost 2014; 40(06): 669-674
DOI: 10.1055/s-0034-1387882
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inflammatory Response and Thrombosis in Older Individuals

Jeffrey Schlaudecker
1   Office of Geriatric Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio
,
Richard Becker
2   Division of Cardiovascular Health and Disease, Heart, Lung, and Vascular Institute, University of Cincinnati College of Medicine, Cincinnati, Ohio
› Author Affiliations
Further Information

Publication History

Publication Date:
24 August 2014 (online)

Abstract

The available evidence suggests that immunosenescence induces organismal proinflammatory responses. The chronic inflammation seen in advancing age stratifies persons into aging phenotypes. Even with adjustment for confounders, elevated inflammatory cytokines significantly decrease the odds of successful aging. This chronic inflammation seen in advancing age has varied causes, including comorbid illness, adipose tissue mass, diet, socioeconomic status, body mass index, gender, age, and physical activity. Aging can therefore be thought of as an acquired thrombophilia of increasing inflammation, impaired fibrinolytic potential, and a hypercoagulable state, out of proportion to physiological needs. Factors ranging from genetic to environmental contribute to the prothrombotic tendency of aging adults, especially those with concomitant frailty, to experience a decline in health status.

 
  • References

  • 1 Gharacholou SM, Becker RC. Hemostasis and thrombosis in older adults. J Thromb Thrombolysis 2009; 27 (2) 249-251
  • 2 Pretorius E, Oberholzer HM, van der Spuy WJ, Meiring JH. Age-related changes in fibrin networks and platelets of individuals over 75: a scanning electron microscopy study showing “thrombotic preparedness”. J Thromb Thrombolysis 2010; 29 (3) 271-275
  • 3 Olivieri F, Procopio AD, Montgomery RR. Effect of aging on microRNAs and regulation of pathogen recognition receptors. Curr Opin Immunol 2014; 29C: 29-37
  • 4 Jenny NS, French B, Arnold AM , et al. Long-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars. J Gerontol A Biol Sci Med Sci 2012; 67 (9) 970-976
  • 5 Akbaraly TN, Hamer M, Ferrie JE , et al. Chronic inflammation as a determinant of future aging phenotypes. CMAJ 2013; 185 (16) E763-E770
  • 6 Hubbard RE, O'Mahony MS, Savva GM, Calver BL, Woodhouse KW. Inflammation and frailty measures in older people. J Cell Mol Med 2009; 13 0B 3103-3109
  • 7 Akbaraly T, Sabia S, Hagger-Johnson G , et al. Does overall diet in midlife predict future aging phenotypes? A cohort study. Am J Med 2013; 126 (5) 411-419 , e3
  • 8 Kuczmarski MF, Mason MA, Allegro D, Zonderman AB, Evans MK. Diet quality is inversely associated with C-reactive protein levels in urban, low-income African-American and white adults. J Acad Nutr Diet 2013; 113 (12) 1620-1631
  • 9 Deverts DJ, Cohen S, Kalra P, Matthews KA. The prospective association of socioeconomic status with C-reactive protein levels in the CARDIA study. Brain Behav Immun 2012; 26 (7) 1128-1135
  • 10 Schafer MH, Ferraro KF, Williams SR. Low socioeconomic status and body mass index as risk factors for inflammation in older adults: conjoint influence on C-reactive protein?. J Gerontol A Biol Sci Med Sci 2011; 66 (6) 667-673
  • 11 Hamer M, Sabia S, Batty GD , et al. Physical activity and inflammatory markers over 10 years: follow-up in men and women from the Whitehall II cohort study. Circulation 2012; 126 (8) 928-933
  • 12 Tiainen K, Hurme M, Hervonen A, Luukkaala T, Jylhä M. Inflammatory markers and physical performance among nonagenarians. J Gerontol A Biol Sci Med Sci 2010; 65 (6) 658-663
  • 13 Exploring the biological contributions to human health: does sex matter?. J Womens Health Gend Based Med 2001; 10 (5) 433-439
  • 14 Yang Y, Kozloski M. Sex differences in age trajectories of physiological dysregulation: inflammation, metabolic syndrome, and allostatic load. J Gerontol A Biol Sci Med Sci 2011; 66 (5) 493-500
  • 15 Tofler GH, Massaro J, Levy D , et al. Relation of the prothrombotic state to increasing age (from the Framingham Offspring Study). Am J Cardiol 2005; 96 (9) 1280-1283
  • 16 Cohen HJ, Harris T, Pieper CF. Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly. Am J Med 2003; 114 (3) 180-187
  • 17 Walston J, McBurnie MA, Newman A , et al; Cardiovascular Health Study. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med 2002; 162 (20) 2333-2341
  • 18 Franchini M. Hemostasis and aging. Crit Rev Oncol Hematol 2006; 60 (2) 144-151
  • 19 Leng SX, Cappola AR, Andersen RE , et al. Serum levels of insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clin Exp Res 2004; 16 (2) 153-157
  • 20 Wilkerson WR, Sane DC. Aging and thrombosis. Semin Thromb Hemost 2002; 28 (6) 555-568
  • 21 Yamamoto K, Takeshita K, Kojima T, Takamatsu J, Saito H. Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly. Cardiovasc Res 2005; 66 (2) 276-285
  • 22 Bonfigli AR, Sirolla C, Cenerelli S , et al. Plasminogen activator inhibitor-1 plasma level increases with age in subjects with the 4G allele at position -675 in the promoter region. Thromb Haemost 2004; 92 (5) 1164-1165
  • 23 Hamsten A, de Faire U, Walldius G , et al. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2 (8549) 3-9
  • 24 Wilson JF. Frailty—and its dangerous effects—might be preventable. Ann Intern Med 2004; 141 (6) 489-492
  • 25 Hamsten A, Wiman B, de Faire U, Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313 (25) 1557-1563
  • 26 Yost CC, Cody MJ, Harris ES , et al. Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates. Blood 2009; 113 (25) 6419-6427
  • 27 Kotronen A, Joutsi-Korhonen L, Sevastianova K , et al. Increased coagulation factor VIII, IX, XI and XII activities in non-alcoholic fatty liver disease. Liver Int 2011; 31 (2) 176-183
  • 28 Willenberg T, Schumacher A, Amann-Vesti B , et al. Impact of obesity on venous hemodynamics of the lower limbs. J Vasc Surg 2010; 52 (3) 664-668
  • 29 Cushman M, Callas PW, Denenberg JO, Bovill EG, Criqui MH. Risk factors for peripheral venous disease resemble those for venous thrombosis: the San Diego Population Study. J Thromb Haemost 2010; 8 (8) 1730-1735
  • 30 Severinsen MT, Overvad K, Johnsen SP , et al. Genetic susceptibility, smoking, obesity and risk of venous thromboembolism. Br J Haematol 2010; 149 (2) 273-279
  • 31 Goldhaber SZ, Grodstein F, Stampfer MJ , et al. A prospective study of risk factors for pulmonary embolism in women. JAMA 1997; 277 (8) 642-645
  • 32 Blaszyk H, Wollan PC, Witkiewicz AK, Björnsson J. Death from pulmonary thromboembolism in severe obesity: lack of association with established genetic and clinical risk factors. Virchows Arch 1999; 434 (6) 529-532
  • 33 Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med 2005; 118 (9) 978-980
  • 34 Poirier P, Giles TD, Bray GA , et al; American Heart Association, Obesity Committee of the Council on Nutrition, Physical Activity, and 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 (6) 898-918
  • 35 Grignani G, Maiolo A. Cytokines and hemostasis. Haematologica 2000; 85 (9) 967-972
  • 36 Suganami T, Nishida J, Ogawa Y. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 2005; 25 (10) 2062-2068
  • 37 Engström G, Hedblad B, Stavenow L , et al. Incidence of obesity-associated cardiovascular disease is related to inflammation-sensitive plasma proteins: a population-based cohort study. Arterioscler Thromb Vasc Biol 2004; 24 (8) 1498-1502
  • 38 Schernthaner GH, Kopp HP, Krzyzanowska K, Kriwanek S, Koppensteiner R, Schernthaner G. Soluble CD40L in patients with morbid obesity: significant reduction after bariatric surgery. Eur J Clin Invest 2006; 36 (6) 395-401
  • 39 Goichot B, Grunebaum L, Desprez D , et al. Circulating procoagulant microparticles in obesity. Diabetes Metab 2006; 32 (1) 82-85
  • 40 Smith NL, Rice KM, Bovill EG , et al. Genetic variation associated with plasma von Willebrand factor levels and the risk of incident venous thrombosis. Blood 2011; 117 (22) 6007-6011
  • 41 den Hoed M, Ekelund U, Brage S , et al. Genetic susceptibility to obesity and related traits in childhood and adolescence: influence of loci identified by genome-wide association studies. Diabetes 2010; 59 (11) 2980-2988
  • 42 Freedman JE, Larson MG, Tanriverdi K , et al. Relation of platelet and leukocyte inflammatory transcripts to body mass index in the Framingham heart study. Circulation 2010; 122 (2) 119-129
  • 43 Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287 (3) 356-359
  • 44 Beavers KM, Hsu FC, Houston DK , et al; Health ABC Study. The role of metabolic syndrome, adiposity, and inflammation in physical performance in the Health ABC Study. J Gerontol A Biol Sci Med Sci 2013; 68 (5) 617-623
  • 45 Kizer JR, Arnold AM, Jenny NS , et al. Longitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old: the Cardiovascular Health Study All Stars study. J Gerontol A Biol Sci Med Sci 2011; 66 (10) 1100-1107
  • 46 Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004; 145 (5) 2273-2282
  • 47 Ferrucci L, Corsi A, Lauretani F , et al. The origins of age-related proinflammatory state. Blood 2005; 105 (6) 2294-2299
  • 48 Brinkley TE, Hsu FC, Beavers KM , et al. Total and abdominal adiposity are associated with inflammation in older adults using a factor analysis approach. J Gerontol A Biol Sci Med Sci 2012; 67 (10) 1099-1106
  • 49 Cesari M, Kritchevsky SB, Baumgartner RN , et al. Sarcopenia, obesity, and inflammation—results from the trial of angiotensin converting enzyme inhibition and novel cardiovascular risk factors study. Am J Clin Nutr 2005; 82 (2) 428-434
  • 50 Engbers MJ, Blom JW, Cushman M, Rosendaal FR, van Hylckama Vlieg A. The contribution of immobility risk factors to the incidence of venous thrombosis in an older population. J Thromb Haemost 2014; 12 (3) 290-296
  • 51 Dalager-Pedersen M, Søgaard M, Schønheyder HC, Nielsen H, Thomsen RW. M P-D. Risk for myocardial infarction and stroke after community-acquired bacteremia: a 20-year population-based cohort study. Circulation 2014; 129 (13) 1387-1396
  • 52 Connolly-Andersen AM, Hammargren E, Whitaker H , et al. Increased risk of acute myocardial infarction and stroke during hemorrhagic fever with renal syndrome: a self-controlled case series study. Circulation 2014; 129 (12) 1295-1302