High-Sensitivity C-Reactive Protein and Ankle Brachial Index in a Finnish Cardiovascular Risk Population

ABSTRACT

High-sensitivity C-reactive protein (hsCRP) has been previously linked to different forms of vascular disease. However, some studies have not found any relationship between hsCRP and atherosclerosis. Also, studies investigating correlation between hsCRP and ankle brachial index (ABI) are scarce. We studied hsCRP in a cardiovascular risk population with a special interest in correlation between hsCRP and ABI. All men and women aged 45 to 70 years from a rural town Harjavalta, Finland were invited to participate in a population survey. Diabetics and people with known vascular disease were excluded. Seventy-three percent (n = 2085) of the invited persons participated and 70% of the respondents (n = 1496) had at least one risk factor to cardiovascular diseases. These subjects were invited to further examinations. From them we measured ABI, hsCRP, leukocyte count, glucose tolerance, systemic coronary risk evaluation (SCORE), body mass index (BMI), and waist circumference. Mean hsCRP was 1.9 mg/L. Smokers had higher hsCRP (mean 2.2 mg/L) than nonsmokers (mean 1.8 mL/L). hsCRP in women was higher than in men (mean 2.0 mg/L versus 1.8 mg/L). Mean ABI was 1.10, and the prevalence of peripheral arterial disease was 3.1%. ABI correlated weakly with hsCRP (r = −0.077, p = 0.014), leukocyte count (r = −0.107, p = 0.001), and SCORE (r = −0.116, p = 0.001). It did not have correlation between age, weight, BMI, or waist circumference. hsCRP correlated with BMI (r = 0.208, p < 0.0001) and waist circumference (r = 0.325, p < 0.0001). When we excluded subjects with hsCRP >10 mg/L, ABI no longer correlated with hsCRP. In a cardiovascular risk population, hsCRP has only a weak correlation with ABI, and this correlation disappeared when we excluded subject with hsCRP >10 mg/L. Instead, hsCRP was correlated to the measures of obesity (waist circumference and BMI), indicating its role as a marker of adipose tissue–driven inflammation. hsCRP does not seem to be a suitable screening method for peripheral arterial disease.

KEYWORDS

High sensitivity C-reactive protein - ankle brachial index - cardiovascular risk factors

REFERENCES

• 1 Ridker P M, Cushman M, Stampfer M J, Tracy R P, Hennekens C H. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.  N Engl J Med. 1997;  336 973-979
• 2 Ridker P M, Stampfer M J, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease.  JAMA. 2001;  285 2481-2485
• 3 Danesh J, Wheeler J G, Hirschfield G M et al.. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease.  N Engl J Med. 2004;  350 1387-1397
• 4 Pearson T A, Mensah G A, Alexander R W Centers for Disease Control and Prevention et al. 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
• 5 Reilly M P, Wolfe M L, Localio A R, Rader D J. Study of Inherited Risk of Coronary Atherosclerosis . C-reactive protein and coronary artery calcification: The Study of Inherited Risk of Coronary Atherosclerosis (SIRCA).  Arterioscler Thromb Vasc Biol. 2003;  23 1851-1856
• 6 de Maat M P, Bladbjerg E M, Drivsholm T, Borch-Johnsen K, Møller L, Jespersen J. Inflammation, thrombosis and atherosclerosis: results of the Glostrup study.  J Thromb Haemost. 2003;  1 950-957
• 7 Saito M, Ishimitsu T, Minami J, Ono H, Ohrui M, Matsuoka H. Relations of plasma high-sensitivity C-reactive protein to traditional cardiovascular risk factors.  Atherosclerosis. 2003;  167 73-79
• 8 Folsom A R, Pankow J S, Tracy R P Investigators of the NHBLI Family Heart Study et al. Association of C-reactive protein with markers of prevalent atherosclerotic disease.  Am J Cardiol. 2001;  88 112-117
• 9 Elias-Smale S E, Kardys I, Oudkerk M et al.. C-reactive protein is related to extent and progression of coronary and extra-coronary atherosclerosis; results from the Rotterdam study.  Atherosclerosis. 2007;  195 e195-e202
• 10 Shankar A, Li J, Nieto F J, Klein B E, Klein R. Association between C-reactive protein level and peripheral arterial disease among US adults without cardiovascular disease, diabetes, or hypertension.  Am Heart J. 2007;  154 495-501
• 11 Vu J D, Vu J B, Pio J R et al.. Impact of C-reactive protein on the likelihood of peripheral arterial disease in United States adults with the metabolic syndrome, diabetes mellitus, and preexisting cardiovascular disease.  Am J Cardiol. 2005;  96 655-658
• 12 Lindström J, Tuomilehto J. The diabetes risk score: a practical tool to predict type 2 diabetes risk.  Diabetes Care. 2003;  26 725-731
• 13 Conroy R M, Pyörälä K, Fitzgerald A P SCORE project group et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.  Eur Heart J. 2003;  24 987-1003
• 14 Parati G, Stergiou G S, Asmar R ESH Working Group on Blood Pressure Monitoring et al. European Society of Hypertension guidelines for blood pressure monitoring at home: a summary report of the Second International Consensus Conference on Home Blood Pressure Monitoring.  J Hypertens. 2008;  26 1505-1526
• 15 World Health Organization (WHO) .Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia. Report of a WHO/IDF Consultation. Geneva, Switzerland: World Health Organization; 2006
• 16 Alberti K G, Zimmet P, Shaw J. IDF Epidemiology Task Force Consensus Group . The metabolic syndrome—a new worldwide definition.  Lancet. 2005;  366 1059-1062
• 17 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults . 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 2486-2497
• 18 Korhonen P, Aarnio P, Saaresranta T, Jaatinen P, Kantola I. Glucose homeostasis in hypertensive subjects.  Hypertension. 2008;  51 945-949
• 19 Pande R L, Perlstein T S, Beckman J A, Creager M A. Association of insulin resistance and inflammation with peripheral arterial disease: the National Health and Nutrition Examination Survey, 1999 to 2004.  Circulation. 2008;  118 33-41
• 20 Eldrup N, Sillesen H, Prescott E, Nordestgaard B G. Ankle brachial index, C-reactive protein, and central augmentation index to identify individuals with severe atherosclerosis.  Eur Heart J. 2006;  27 316-322
• 21 Bo M, Corsinovi L, Brescianini A et al.. High-sensitivity C-reactive protein is not independently associated with peripheral subclinical atherosclerosis.  Angiology. 2009;  60 12-20
• 22 Hak A E, Stehouwer C DA, Bots M L et al.. Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women.  Arterioscler Thromb Vasc Biol. 1999;  19 1986-1991
• 23 Ford E S. Body mass index, diabetes, and C-reactive protein among U.S. adults.  Diabetes Care. 1999;  22 1971-1977
• 24 Planas A, Clará A, Pou J M et al.. Relationship of obesity distribution and peripheral arterial occlusive disease in elderly men.  Int J Obes Relat Metab Disord. 2001;  25 1068-1070
• 25 Despres J P. Abdominal obesity: the most prevalent cause of the metabolic syndrome and related cardiometabolic risk.  Eur Heart J Suppl. 2006;  8 (Suppl B) 4-12
• 26 Carbayo J A, Divisón J A, Escribano J Grupo de Enfermedades Vasculares de Albacete (GEVA) et al. Using ankle-brachial index to detect peripheral arterial disease: prevalence and associated risk factors in a random population sample.  Nutr Metab Cardiovasc Dis. 2007;  17 41-49
• 27 Yanbaeva D G, Dentener M A, Creutzberg E C, Wesseling G, Wouters E F. Systemic effects of smoking.  Chest. 2007;  131 1557-1566
• 28 Thorand B, Baumert J, Döring A KORA Group et al. Sex differences in the relation of body composition to markers of inflammation.  Atherosclerosis. 2006;  184 216-224
• 29 Ahonen T M, Kautiainen H J, Keinänen-Kiukaanniemi S M, Kumpusalo E A, Vanhala M J. Gender difference among smoking, adiponectin, and high-sensitivity C-reactive protein.  Am J Prev Med. 2008;  35 598-601
• 30 Norgren L, Hiatt W R, Dormandy J A et al.. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II).  Eur J Vasc Endovasc Surg. 2007;  33 (Suppl 1) 1-75
• 31 Espinola-Klein C, Rupprecht H J, Bickel C AtheroGene Investigators et al. Different calculations of ankle-brachial index and their impact on cardiovascular risk prediction.  Circulation. 2008;  118 961-967