Skip to main content
Log in

Asymptomatic carotid plaque and pro-inflammatory genetic profile in the elderly

  • Original Articles
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Background and aims: Several indices of subclinical atherosclerosis (ATS), including ultrasound (US) scan of carotid vessels, have received attention in clinical studies of the general population. Since inflammation takes part in the development of ATS, we studied the relationship between US imaging of carotid vessels and genetic predisposition to inflammation, in both elderly subjects without acknowledged CV risk factors and elderly subjects with acknowledged CV risk factors undergoing primary prevention. Methods: Seventy-two elderly subjects (aged between 65–84) were divided into three groups on the basis of cardiovascular (CV) risk (GO: 0–9%, G1: 10–20% and G2: >20%) according to the NCEP Adult Panel III Report. They underwent US evaluation of carotid arteries and were analyzed for single nucleotide polymorphisms in the genes of a number of cytokines: TNF-α, TGF-β1, IL-10, IL-6 and IFN-γ. Results: Asymptomatic carotid plaque (ACP) was detected in 19 subjects, not only in those belonging to the major risk group (36.8%) but also in those at lower risk (63.2%). In these subjects, we found a different genotype distribution in the polymorphisms of IFN-γ (+874), IL-6 (−174) and IL-10 (−1082). The TT +874 IFN-γ and GG -174 IL-6 high producer-genotypes and the AA IL-10 low producer-genotype were indeed more frequent in the ACP group (IFN-γ. p=0.000 and IL-6: p=0.004). We found no correlation between genotype and carotid intima-media thickening. Conclusions: Our data suggest that, in the elderly, inflammation-associated polymorphisms are related to atherogenesis and that the finding of ACP on US scan can be valuable in identifying subjects at risk for CV events, even if they lack traditional cardiovascular risk factors such as an increase in IMT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Braunwald E. Shattuck lecture — cardiovascular medicine at the turn of the millennium: triumphs, concerns, and the oppurtinity. N Engl J Med 1997; 337: 1360–9.

    Article  PubMed  CAS  Google Scholar 

  2. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105: 1135–43.

    Article  PubMed  CAS  Google Scholar 

  3. Ridker PM, Morrow DA. C-reactive protein, inflammation, and coronary risk. Cardiol Clin 2003; 21: 315–25.

    Article  PubMed  Google Scholar 

  4. Ridker PM, Rifai N, Stanpfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000; 101: 1767–72.

    Article  PubMed  CAS  Google Scholar 

  5. Lindmark E, Diderholm E, Wallentin L, Siegbahn A. Relationship between interleukin-6 and mortality in patients with unstable coronary artery disease: effects of an early invasive or non invasive strategy. JAMA 2001; 286: 2107–13.

    Article  PubMed  CAS  Google Scholar 

  6. Boekholdt SM, Peters RJG, Hack CE et al. IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk Prospective Population Study. Arterioscler Thromb Vasc Biol 2004; 24: 1503–8.

    Article  PubMed  CAS  Google Scholar 

  7. Taylor AJ, Merz CN, Udelson JE. 34th Bethesda Conference: Executive summary — can atherosclerosis imaging techniques improve the detection of patients at risk of ischémic heart disease? J Am Coll Cardiol 2003; 41: 1860–2.

    Article  PubMed  Google Scholar 

  8. Burke GL, Evans GW, Riley WA et al. Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults. The Atherosclerosis Risk in Communities (ARIC) Study. Stroke 1995; 26: 386–91.

    Article  PubMed  CAS  Google Scholar 

  9. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 1999; 340: 14–22.

    Article  PubMed  Google Scholar 

  10. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbe DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 1997; 96: 1432–7.

    Article  PubMed  CAS  Google Scholar 

  11. Schillinger M, Exner M, Mlekusch W et al. Inflammation and carotid artery — Risk of Atherosclerosis Study (ICARAS). Circulation 2005; 111: 2203–9.

    Article  PubMed  Google Scholar 

  12. Homma S, Ishii T, Tsugane S, Hirose N. Different effects of hypertension and hypercholesterolemia on the natural history of aortic atherosclerosis by the stages of intimai lesions. Atherosclerosis 1997; 125: 85–95.

    Article  Google Scholar 

  13. Homma S, Hirose N, Ishida H, Ishii T, Araki G. Carotid plaque and intima-media thickness assessed by B-mode ultrasonography in subjects ranging from young adults to centenarians. Stroke 2001; 32: 830–5.

    Article  PubMed  CAS  Google Scholar 

  14. Milio G, Corrado E, Sorrentino D et al. Asymptomatic carotid lesions and aging: role of hypertension and other traditional and emerging risk factors. Arch Med Res 2006; 37: 342–7.

    Article  PubMed  Google Scholar 

  15. Espinola-Klein C, Rupprecht HJ, Blankenberg S et al. Impact of infectious burden on progression of carotid atherosclerosis. Stroke 2002; 33: 2581–6.

    Article  PubMed  CAS  Google Scholar 

  16. Espinola-Klein C, Rupprecht HJ, Blankenberg S et al. Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumonie, Helicobacter pylori, cytomegalovirus, or Herpes simplex virus infection? Stroke 2000; 31: 2127–33.

    Article  PubMed  CAS  Google Scholar 

  17. National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III), final report. Circulation 2002; 106: 3143–421.

    Google Scholar 

  18. Staikov IN, Nedeltchev K, Arnold M et al. Duplex sonographic criteria for measuring carotid stenoses. J Clin Ultrasound 2002; 30: 275–81.

    Article  PubMed  Google Scholar 

  19. Miller SA, Dykes DD, Polesky HFA. Simple salting-out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res 1988; 16: 1215.

    Article  PubMed  CAS  Google Scholar 

  20. Arosio B, Trabattoni D, Galimberti L et al. Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer’s disease. Neurobiol Aging 2004; 25: 1009–15.

    Article  PubMed  CAS  Google Scholar 

  21. Dabora SL, Roberts P, Nieto A et al. Association between a high-expressing interferon-gamma allele and a lower frequency of kidney angiomyolipomas in TSC2 patients. Am J Human Genet 2002; 71: 750–8.

    Article  Google Scholar 

  22. Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 2000; 275: 18138–44.

    Article  PubMed  CAS  Google Scholar 

  23. Kim JM, Brannan CI, Copeland NG, Jenkins NA, Khan TA, Moore KW. Structure of the mouse IL-10 gene and chromosomal localisation of the mouse and human genes. J Immunol 1992; 148: 3618.

    PubMed  CAS  Google Scholar 

  24. 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). JAMA 2001; 285: 2486–97.

    Google Scholar 

  25. Jarvisalo MJ, Juonala M, Raitakari OT. Assessment of inflammatory markers and endothelial function. Curr Opin Clin Nutr Metab Care 2006; 9: 547–52.

    Article  PubMed  CAS  Google Scholar 

  26. Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 2006; 86: 515–81.

    Article  PubMed  CAS  Google Scholar 

  27. Giacconi R, Caruso C, Malavolta M et al. Pro-inflammatory genetic background and zinc status in old atherosclerotic subjects. Ageing Res Rev 2008; doi:10.1016/j.arr.2008.06.001

  28. Markus HS, Labrum R, Bevan S et al. Genetic and acquired inflammatory conditions are synergistically associated with early carotid atherosclerosis. Stroke 2006; 37: 2253–9.

    Article  PubMed  CAS  Google Scholar 

  29. Sabeti S, Schlager O, Exner M et al. Progression of carotid stenosis detected by duplex ultrasonography predicts adverse outcomes in cardiovascular high-risk patients. Stroke 2007; 38: 2887–94.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Giorgio Annoni MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Annoni, G., Annoni, F., Arosio, B. et al. Asymptomatic carotid plaque and pro-inflammatory genetic profile in the elderly. Aging Clin Exp Res 21, 431–436 (2009). https://doi.org/10.1007/BF03327450

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03327450

Keywords

Navigation