Plasma procalcitonin is associated with all-cause and cancer mortality in apparently healthy men: a prospective population-based study

BMC Medicine

Alexandru Schiopu¹  Olle Melander³  Gunnar Engström³  Bo Hedblad³  Jonas Manjer³  Ovidiu S Cotoi² 

[1] Cardiology Clinic, Skane University Hospital, Malmö, Sweden;Department of Cellular and Molecular Biology, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, Romania;Department of Clinical Sciences, Lund University, Lund, Sweden

关键词: Mortality;    CRP;    Cardiovascular disease;    Cancer;    Inflammation;    Procalcitonin;   

Others  :  856943
DOI  :  10.1186/1741-7015-11-180

 received in 2013-02-06, accepted in 2013-06-13,  发布年份 2013

【 摘 要 】

Background

The inflammatory mediator procalcitonin (PCT) has previously been associated with prognosis in myocardial infarction, cancer and sepsis patients. The importance of PCT in the general population is currently unknown. Our aim was to assess the relationship between plasma PCT and the risk of all-cause and cause-specific mortality in apparently healthy individuals with no previous history of cardiovascular disease or cancer.

Methods

We performed a prospective, population-based study on 3,322 individuals recruited from the Malmö Diet and Cancer cohort, with a median follow-up time of 16.2 years. Plasma PCT, high-sensitivity C-reactive protein (hsCRP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides and cystatin C were measured at baseline and a thorough risk factor assessment was performed for all subjects. The primary end-points of the study were all-cause mortality, cancer mortality and cardiovascular mortality.

Results

Men had higher PCT levels compared to women. In Cox proportional hazard models adjusted for age, sex, hypertension, diabetes, plasma lipids, renal function, body mass index and smoking, baseline PCT was associated with all-cause mortality and cancer mortality in men. The hazard ratio (HR) for men with PCT levels within the highest compared with the lowest quartile was 1.52 (95% confidence interval (CI) 1.07 to 2.16; P = 0.024) for all-cause mortality and 2.37 (95% CI 1.36 to 4.14; P = 0.006) for cancer mortality. Additionally, men with increased plasma PCT were found to be at a higher risk to develop colon cancer (HR per 1 SD increase = 1.49 (95% CI 1.13 to 1.95); P = 0.005). In multivariate Cox regression analyses with mutual adjustments for PCT and hsCRP, PCT was independently associated with cancer death (HR per 1 SD increase = 1.28 (95% CI 1.10 to 1.49); P = 0.001) and hsCRP with cardiovascular death (HR per 1 SD increase = 1.42 (95% CI 1.11 to 1.83); P = 0.006) in men. We found no significant correlations between baseline PCT or hsCRP and incident cancer or cardiovascular death in women.

Conclusions

We disclose for the first time important independent associations between PCT and the risk for all-cause and cancer mortality in apparently healthy men. Our findings warrant further investigation into the mechanisms underlying the relationship between PCT and cancer.

【 授权许可】

   
2013 Cotoi et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Libby P, Ridker PM, Hansson GK: Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 2009, 54:2129-2138.
• [2]Coussens LM, Werb Z: Inflammation and cancer. Nature 2002, 420:860-867.
• [3]Malle E, Marsche G, Panzenboeck U, Sattler W: Myeloperoxidase-mediated oxidation of high-density lipoproteins: fingerprints of newly recognized potential proatherogenic lipoproteins. Arch Biochem Biophys 2006, 445:245-255.
• [4]Yeboah J, McClelland RL, Polonsky TS, Burke GL, Sibley CT, O’Leary D, Carr JJ, Goff DC, Greenland P, Herrington DM: Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA 2012, 308:788-795.
• [5]Franks AL, Slansky JE: Multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases and cancer. Anticancer Res 2012, 32:1119-1136.
• [6]Allin KH, Nordestgaard BG: Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci 2011, 48:155-170.
• [7]Ko YJ, Kwon YM, Kim KH, Choi HC, Chun SH, Yoon HJ, Goh E, Cho B, Park M: High-sensitivity C-reactive protein levels and cancer mortality. Cancer Epidemiol Biomarkers Prev 2012, 21:2076-2086.
• [8]Koenig W, Khuseyinova N, Baumert J, Meisinger C: Prospective study of high-sensitivity C-reactive protein as a determinant of mortality: results from the MONICA/KORA Augsburg cohort study, 1984–1998. Clin Chem 2008, 54:335-342.
• [9]Becker KL, Nylen ES, White JC, Muller B, Snider RH Jr: Clinical review 167: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 2004, 89:1512-1525.
• [10]Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C: High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993, 341:515-518.
• [11]Snider RH Jr, Nylen ES, Becker KL: Procalcitonin and its component peptides in systemic inflammation: immunochemical characterization. J Investig Med 1997, 45:552-560.
• [12]Brunkhorst FM, Wegscheider K, Forycki ZF, Brunkhorst R: Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis, and septic shock. Intensive Care Med 2000, 26:S148-S152.
• [13]Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, Neidert S, Fricker T, Blum C, Schild U, Regez K, Schoenenberger R, Henzen C, Bregenzer T, Hoess C, Krause M, Bucher HC, Zimmerli W, Mueller B, ProHOSP Study Group: Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009, 302:1059-1066.
• [14]Muller B, White JC, Nylen ES, Snider RH, Becker KL, Habener JF: Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab 2001, 86:396-404.
• [15]Becker KL, Snider R, Nylen ES: Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target. Br J Pharmacol 2010, 159:253-264.
• [16]Liappis AP, Gibbs KW, Nylen ES, Yoon B, Snider RH, Gao B, Becker KL: Exogenous procalcitonin evokes a pro-inflammatory cytokine response. Inflamm Res 2011, 60:203-207.
• [17]Wiedermann FJ, Kaneider N, Egger P, Tiefenthaler W, Wiedermann CJ, Lindner KH, Schobersberger W: Migration of human monocytes in response to procalcitonin. Crit Care Med 2002, 30:1112-1117.
• [18]Schiopu A, Hedblad B, Engstrom G, Struck J, Morgenthaler NG, Melander O: Plasma procalcitonin and the risk of cardiovascular events and death: a prospective population-based study. J Intern Med 2012, 272:484-491.
• [19]Berglund G, Elmstahl S, Janzon L, Larsson SA: The Malmo Diet and Cancer Study. Design and feasibility. J Intern Med 1993, 233:45-51.
• [20]Hedblad B, Nilsson P, Janzon L, Berglund G: Relation between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects. Results from a cross-sectional study in Malmo, Sweden. Diabet Med 2000, 17:299-307.
• [21]Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, Heurgren M, Olausson PO: External review and validation of the Swedish national inpatient register. BMC Publ Health 2011, 11:450. BioMed Central Full Text
• [22]Hammar N, Alfredsson L, Rosen M, Spetz CL, Kahan T, Ysberg AS: A national record linkage to study acute myocardial infarction incidence and case fatality in Sweden. Int J Epidemiol 2001, 30:S30-S34.
• [23]Charbonney E, Terrettaz M, Vuilleumier N, Lambert JF: Acute chest syndrome in sickle cell disease and acute respiratory distress syndrome--from pathophysiology to therapy. Rev Med Suisse 2006, 2:2852-2857.
• [24]Meisner M, Lohs T, Huettemann E, Schmidt J, Hueller M, Reinhart K: The plasma elimination rate and urinary secretion of procalcitonin in patients with normal and impaired renal function. Eur J Anaesthesiol 2001, 18:79-87.
• [25]Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003, 348:1625-1638.
• [26]Gandini S, Botteri E, Iodice S, Boniol M, Lowenfels AB, Maisonneuve P, Boyle P: Tobacco smoking and cancer: a meta-analysis. Int J Cancer 2008, 122:155-164.
• [27]Walter MA, Meier C, Radimerski T, Iten F, Kranzlin M, Muller-Brand J, de Groot JW, Kema IP, Links TP, Muller B: Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer. Cancer 2010, 116:31-40.
• [28]Jimeno A, Garcia-Velasco A, del Val O, Gonzalez-Billalabeitia E, Hernando S, Hernandez R, Sanchez-Munoz A, Lopez-Martin A, Duran I, Robles L, Cortés-Funes H, Paz-Ares L: Assessment of procalcitonin as a diagnostic and prognostic marker in patients with solid tumors and febrile neutropenia. Cancer 2004, 100:2462-2469.
• [29]Shomali W, Hachem R, Chaftari AM, Jiang Y, Bahu R, Jabbour J, Raad S, Al Shuaibi M, Al Wohoush I, Raad I: Can procalcitonin distinguish infectious fever from tumor-related fever in non-neutropenic cancer patients? Cancer 2012, 118:5823-5829.
• [30]Kuper H, Adami HO, Trichopoulos D: Infections as a major preventable cause of human cancer. J Intern Med 2000, 248:171-183.
• [31]Maeda H, Akaike T: Nitric oxide and oxygen radicals in infection, inflammation, and cancer. Biochemistry (Mosc) 1998, 63:854-865.
• [32]Nylen ES, Whang KT, Snider RH Jr, Steinwald PM, White JC, Becker KL: Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis. Crit Care Med 1998, 26:1001-1006.
• [33]Redl H, Schiesser A, Togel E, Assicot M, Bohuon C: Possible role of TNF on procalcitonin release in a baboon model of sepsis. Shock 2001, 16:25-27.
• [34]Whang KT, Vath SD, Becker KL, Snider RH, Nylen ES, Muller B, Li Q, Tamarkin L, White JC: Procalcitonin and proinflammatory cytokine interactions in sepsis. Shock 2000, 14:73-78.
• [35]Lin WW, Karin M: A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007, 117:1175-1183.
• [36]Ullman TA, Itzkowitz SH: Intestinal inflammation and cancer. Gastroenterology 2011, 140:1807-1816.
• [37]Klampfer L: Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets 2011, 11:451-464.