Lymphocytes ≥ 2.9 (10⁹/L) in Newly Diagnosed Diabetes Are A Predictor of Future CVD Events

Abstract

Objective

Atherosclerosis is considered a chronic inflammatory condition. The immune system is a key mediator in the initiation and progression of atherosclerosis. In a previous study, we found that the immune system was activated in diabetes and that total white blood cell (WBC) counts were elevated significantly in diabetic patients. To investigate whether WBC subtype counts in newly diagnosed diabetes are risk factors for future cardiovascular disease (CVD) events, we conducted a prospective population-based cohort study.

Methods

A total of 1498 newly diagnosed diabetic patients aged 40 to 70 years old were followed up for three years. Participants with previous CVD history and abnormal WBC counts were excluded. CVD events were recorded during follow-up.

Results

We found that the baseline lymphocyte counts were independently associated with cardiovascular events during follow-up, with the Exp (β) (95% CI) at 1.749 (1.084–2.821). Lymphocyte count ≥2.9 (10⁹/L) was significantly associated with the development of CVD (HR, 2.29; 95% CI, 1.12–4.67). The corresponding incidence of CVD per 1000 person-year for the lymphocyte count ≤2.8 (10⁹/L) and lymphocyte count ≥2.9 (10⁹/L) groups were 11.26 and 26.38, respectively.

Conclusion

We concluded that even in a normal range, higher lymphocyte levels may result in a significantly higher CVD risk among diabetic patients. Lymphocyte count ≥2.9 (10⁹/L) is an independent predictor of developing future CVD events.

Keywords

lymphocytes / risk / cardiovascular events / diabetes

References

[1] AlvarezCA, LingvayI, VuylstekeV, et al.. Cardiovascular Risk in Diabetes Mellitus: Complication of the Disease or of Antihyperglycemic Medications. Clin Pharmacol Ther, 2015, 98(2): 145-161

[2] TousoulisD, PsarrosC, DemosthenousM, et al.. Innate and adaptive inflammation as a therapeutic target in vascular disease: the emerging role of statins. J Am Coll Cardiol, 2014, 63(23): 2491-2502

[3] Fernandez-RealJM, PickupJC. Innate immunity, insulin resistance and type 2 diabetes. Diabetologia, 2012, 55(2): 273-278

[4] ZhangH, YangZ, ZhangW, et al.. White blood cell subtypes and risk of type 2 diabetes. J Diabetes Complications, 2017, 31(1): 31-37

[5] NingG, Reaction StudyG. Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. J Diabetes, 2012, 4(2): 172-173

[6] BiY, LuJ, WangW, et al.. Cohort profile: risk evaluation of cancers in Chinese diabetic individuals: a longitudinal (REACTION) study. J Diabetes, 2014, 6(2): 147-157

[7] CampRL, Dolled-FilhartM, RimmDL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res, 2004, 10(21): 7252-7259

[8] HowardBV, MageeMF. Diabetes and cardiovascular disease. Current atherosclerosis reports, 2000, 2(6): 476-481

[9] LegeinB, TemmermanL, BiessenEA, et al.. Inflammation and immune system interactions in atherosclerosis. Cell Mol Life Sci, 2013, 70(20): 3847-3869

[10] MendisSPN, B. Global Atlas on cardiovascular disease prevention and control, 2011, Geneva, WHO

[11] American DiabetesA. 9. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2018. Diabetes care, 2018, 41(Suppl 1): S86-S104

[12] BrunettiND. ‘Hot stuff’: inflammatory lymphocyte populations in acute coronary syndrome. Cell Mol Immunol, 2015, 12(4): 513-514

[13] HanssonGK, HolmJ, JonassonL. Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol, 1989, 135(1): 169-175

[14] SongL, LeungC, SchindlerC. Lymphocytes are important in early atherosclerosis. J Clin Invest, 2001, 108(2): 251-259