Download PDF
Thromb Haemost 2017; 117(06): 1129-1140
DOI: 10.1160/TH16-12-0974
Cellular Haemostasis and Platelets
Schattauer GmbH

Mean platelet volume is associated with lower risk of overall and non-vascular mortality in a general population

Results from the Moli-sani study
Marialaura Bonaccio
1   Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy
,
Augusto Di Castelnuovo
1   Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy
,
Simona Costanzo
1   Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy
,
Amalia De Curtis
1   Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy
,
Mariarosaria Persichillo
1   Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy
,
Chiara Cerletti
1   Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy
,
Maria Benedetta Donati
1   Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy
,
Giovanni de Gaetano
1   Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy
,
Licia Iacoviello
1   Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy
2   Department of Medicine and Surgery, University of Insubria, Varese, Italy
,
the Moli-sani Study Investigators › Author Affiliations Financial support: The enrolment phase of the Moli-sani study was supported by research grants from Pfizer Foundation (Rome, Italy), the Italian Ministry of University and Research (MIUR, Rome, Italy)–Programma Triennale di Ricerca, Decreto no.1588 and Instrumentation Laboratory, Milan, Italy. Funders had no role in study design, collection, analysis, and interpretation of data; in the writing of the manuscript and in the decision to submit the article for publication. Marialaura Bonaccio was supported by a Fondazione Umberto Veronesi Fellowship. All Authors were and are independent from funders. The present analyses were partially supported by the Italian Ministry of Health 2013 (Young investigator grant to MB, number: GR-2013–02356060) and by the Italian Association for Cancer Research (A. I. R. C.) with grant AIRC “5 × 1000” Ref. n. 12237.
Further Information

Publication History

Received: 30 December 2016

Accepted after major revision: 19 March 2017

Publication Date:
28 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Larger mean platelet volume (MPV) has been associated with adverse health outcomes in high-risk populations or patients with cardiovascular disease (CVD). We tested the association of MPV with mortality in a prospective cohort study including 17,402 subjects randomly recruited from an adult general population within the Moli-sani study (2005–2010). Two distinct subgroups (with or without CVD at baseline) were subsequently analysed. Hazard ratios (HR) were calculated using multivariable Cox-proportional hazard models. Over a median follow up of eight years (137,547 person-years), 925 all-cause deaths occurred (330 vascular, 351 cancer and 244 other deaths). In a multivariable model, the highest MPV quintile (mean MPV=10.0 fL), as compared to the lowest one, was associated with reduced risk of overall mortality (HR=0.79; 95 % confidence interval 0.64–0.98), cancer death (HR=0.70; 0.49–1.00) and death from other non- vascular/non cancer causes (HR=0.55; 0.36–0.84) but not with vascular mortality. The inverse association with overall death appeared even stronger in the subgroup without CVD at baseline (HR=0.64; 0.50–0.81). In contrast, within 920 subjects reporting a previous CVD event, larger MPV was associated with higher risk of total mortality (HR=1.69; 1.05–2.72; p for interaction=0.048) and with a trend of risk for other cause-specific deaths. In conclusion, larger MPV is associated with lower risk of overall and non-vascular death in subjects apparently free from CVD, but appears to be a predictive marker of death in patients with CVD history. The latter is a likely effect modifier of the association between MPV and death.

Keywords

Mean platelet volume - mortality - epidemiology - cardiovascular disease - cerebrovascular disease

* Moli-sani study Investigators are listed in Appendix.


 

  • References

  • 1 de Gaetano G. A new blood corpuscle: an impossible interview with Giulio Bizzozero. Thromb Haemost 2001; 86: 973-979.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Koenen RR. The prowess of platelets in immunity and inflammation. Thromb Haemost 2016; 116: 605-612.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Morrell CN, Aggrey AA, Chapman LM. at al. Emerging roles for platelets as immune and inflammatory cells. Blood 2014; 123: 2759-2767.
    CrossrefPubMedGoogle Scholar
  • 4 Bonaccio M, Di Castelnuovo A, De Curtis A. et al. Adherence to the Mediterranean diet is associated with lower platelet and leukocyte counts: results from the Moli-sani study. Blood 2014; 123: 3037-3044.
    CrossrefPubMedGoogle Scholar
  • 5 Leblanc R, Peyruchaud O. Metastasis: new functional implications of platelets and megakaryocytes. Blood 2016; 128: 24-31.
    CrossrefPubMedGoogle Scholar
  • 6 Panova-Noeva M, Schulz A, Hermanns MI. et al. Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study. Blood 2016; 127: 251-259.
    CrossrefPubMedGoogle Scholar
  • 7 Park Y, Schoene N, Harris W. Mean platelet volume as an indicator of platelet activation: methodological issues. Platelets 2002; 13: 301-306.
    CrossrefPubMedGoogle Scholar
  • 8 Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol 2006; 47 (Suppl. 08) C7-12.
    CrossrefPubMedGoogle Scholar
  • 9 Massberg S, Schulz C, Gawaz M. Role of platelets in the pathophysiology of acute coronary syndrome. Semin Vasc Med 2003; 3: 147-162.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Ranjith MP, DivyaRaj R, Mathew D. et al. Mean platelet volume and cardiovascular outcomes in acute myocardial infarction. Heart Asia 2016; 8: 16-20.
    CrossrefPubMedGoogle Scholar
  • 11 Sun XP, Li BY, Li J. et al. Impact of Mean Platelet Volume on Long-Term Mortality in Chinese Patients with ST-Elevation Myocardial Infarction. Sci Rep 2016; 6: 21350.
    CrossrefPubMedGoogle Scholar
  • 12 Pereg D, Berlin T, Mosseri M. Mean platelet volume on admission correlates with impaired response to thrombolysis in patients with ST-elevation myocardial infarction. Platelets 2010; 21: 117-121.
    CrossrefPubMedGoogle Scholar
  • 13 Kılınçalp S, Ekiz F, Ba ar O. et al. Mean platelet volume could be possible biomarker in early diagnosis and monitoring of gastric cancer. Platelets 2014; 25: 592-594.
    CrossrefPubMedGoogle Scholar
  • 14 Kalkan ME, Açar G, Sahin M. et al. Mean platelet volume levels in patients with cardiac myxoma. Platelets 2014; 25: 587-591.
    CrossrefPubMedGoogle Scholar
  • 15 Chu SG, Becker RC, Berger PB. et al. Mean platelet volume as a predictor of cardiovascular risk: a systematic review and metanalysis. J Thromb Haemost 2010; 8: 148-156.
    CrossrefPubMedGoogle Scholar
  • 16 Greisenegger S, Endler G, Hsieh K. et al. Is elevated mean platelet volume associated with a worse outcome in patients with acute ischemic cerebrovascular events?. Stroke 2004; 35: 1688-1691.
    CrossrefPubMedGoogle Scholar
  • 17 Braekkan SK, Mathiesen EB, Njølstad I. et al. Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø Study, Tromsø, Norway. J Thromb Haemost 2010; 8: 157-162.
    CrossrefPubMedGoogle Scholar
  • 18 Levin J, Bessman JD. The inverse relation between platelet volume and platelet number. Abnormalities in hematologic disease and evidence that platelet size does not correlate with platelet age. J Lab Clin Med 1983; 101: 295-307.
    PubMedGoogle Scholar
  • 19 Bonaccio M, Di Castelnuovo A, Costanzo S. et al. Age-sex-specific ranges of platelet count and all-cause mortality: prospective findings from the MOLISANI study. Blood 2016; 127: 1614-1616.
    CrossrefPubMedGoogle Scholar
  • 20 Klovaite J, Benn M, Yazdanyar S. et al. High platelet volume and increased risk of myocardial infarction: 39,531 participants from the general population. J Thromb Haemost 2011; 9: 49-56.
    CrossrefPubMedGoogle Scholar
  • 21 Slavka G, Perkmann T, Haslacher H. et al. Mean platelet volume may represent a predictive parameter for overall vascular mortality and ischemic heart disease. Arterioscler Thromb Vasc Biol 2011; 31: 1215-1218.
    CrossrefPubMedGoogle Scholar
  • 22 Di Castelnuovo A, Costanzo S, Persichillo M. et al. Distribution of short and lifetime risks for cardiovascular disease in Italians. Eur J Prev Cardiol 2012; 19: 723-730.
    PubMedGoogle Scholar
  • 23 Pisani P, Faggiano F, Krogh V. et al. Relative validity and reproducibility of a food frequency dietary questionnaire for use in the Italian EPIC centres. Int J Epidemiol 1997; 26 (Suppl. 01) S152-160.
    CrossrefPubMedGoogle Scholar
  • 24 Trichopoulou A, Costacou T, Bamia C. et al. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 2003; 348: 2599-2608.
    CrossrefPubMedGoogle Scholar
  • 25 Santimone I, Di Castelnuovo A, De Curtis A. et al. White blood cell count, sex and age are major determinants of heterogeneity of platelet indices in an adult general population: results from the MOLI-SANI project. Haematologica 2011; 96: 1180-1188.
    CrossrefPubMedGoogle Scholar
  • 26 Biino G, Portas L, Murgia F. et al. A population-based study of an Italian genetic isolate reveals that mean platelet volume is not a risk factor for thrombosis. Thromb Res 2012; 129: e8-13.
    CrossrefPubMedGoogle Scholar
  • 27 Badimon L, Padró T, Vilahur G. Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. Eur Heart J Acute Cardiovasc Care 2012; 1: 60-74.
    CrossrefPubMedGoogle Scholar
  • 28 Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol 2012; 23 (Suppl. 08) viii6-9.
    PubMedGoogle Scholar
  • 29 Adam JK, Odhav B, Bhoola KD. Immune responses in cancer. Pharmacol Ther 2003; 99: 113-132.
    CrossrefPubMedGoogle Scholar
  • 30 Bergmann CB, Hefele F, Unger M. et al. Platelets modulate the immune response following trauma by interaction with CD4+ T regulatory cells in a mouse model. Immunol Res 2016; 64: 508-517.
    CrossrefPubMedGoogle Scholar
  • 31 Gawaz M, Vogel S. Platelets in tissue repair: control of apoptosis and interactions with regenerative cells. Blood 2013; 122: 2550-2554.
    CrossrefPubMedGoogle Scholar
  • 32 Schleicher RI, Reichenbach F, Kraft P. et al. Platelets induce apoptosis via membrane-bound FasL. Blood 2015; 126: 1483-1493.
    CrossrefPubMedGoogle Scholar
  • 33 Luo S, Wang Y, An Q. et al. Platelets protect lung from injury induced by systemic inflammatory response. Sci Rep 2017; 7: 42080.
    CrossrefPubMedGoogle Scholar
  • 34 Li D. Effect of the vegetarian diet on non-communicable diseases. J Sci Food Agric 2014; 94: 169-173.
    CrossrefPubMedGoogle Scholar