Carotid Intima-Media Thickness is a Predictor of Subclinical Myocardial Damage in Men with Type 2 Diabetes Mellitus

Abstract

Background Type 2 diabetes mellitus (T2DM) promotes the development of atherosclerosis and is a major risk factor for cardiovascular disease. High-sensitivity cardiac troponin I (hs-cTnI) assays fundamentally improved the diagnosis of myocardial injury and even enable the prediction of future cardiovascular events in the general population. However, data about the association of hs-cTnI with cardiovascular risk factors and carotid intima media thickness (cIMT) as a marker of atherosclerosis are limited, especially in patients with T2DM.

Methods In this cross-sectional study we analyzed clinical and laboratory parameters of 234 patients (43% women) with T2DM and a median age of 65 years (interquartile range: 57–71). The median duration of diabetes mellitus was 10 years (6–17). Anthropometric data, blood pressure, glycemic parameters and lipid profiles were determined. Hs-cTnI plasma concentrations were measured on an ADVIA Centaur XPT immunoassay analyzer and cIMT was evaluated by high-resolution ultrasound.

Results Hs-cTnI plasma concentrations were below the gender-specific 99^th  percentile in 93% of T2DM patients with a median concentration of 4.0 ng/l (interquartile range: 2.0–10.0). Hs-cTnI was significantly associated with gender, renal function and C-reactive protein in the entire study cohort. Gender-specific analyses revealed cIMT and renal function to be significantly associated with hs-cTnI in men. Contrary, only age was significantly associated with hs-cTnI in women.

Conclusion In a real-world clinical setting in patients with T2DM, cIMT is a predictor of subclinical myocardial damage in men, but not in women.

Key words

High-sensitivity cardiac troponin I - type 2 diabetes mellitus - intima-media thickness, cardiovascular disease

• References

• 1 Everett BM, Brooks MM, Vlachos HE. et al. Troponin and cardiac events in stable ischemic heart disease and diabetes. N Engl J Med 2015; 373: 610-620
• 2 Diabetes mellitus: a major risk factor for cardiovascular disease. A joint editorial statement by the American Diabetes Association; The National Heart, Lung, and Blood Institute; The Juvenile Diabetes Foundation International; The National Institute of Diabetes and Digestive and Kidney Diseases; and The American Heart Association. Circulation 1999; 100: 1132-1133
• 3 Lloyd-Jones DM, Leip EP, Larson MG. et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation 2006; 113: 791-798
• 4 Emerging Risk Factors C, Sarwar N, Gao P. et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: A collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375: 2215-2222
• 5 Thygesen K, Alpert JS, Jaffe AS. et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019; 40: 237-269
• 6 Thygesen K, Mair J, Katus H. et al. Recommendations for the use of cardiac troponin measurement in acute cardiac care. Eur Heart J 2010; 31: 2197-2204
• 7 Damman P, van 't Hof AW, Ten Berg JM. et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Comments from the Dutch ACS working group. Neth Heart J 2017; 25: 181-185
• 8 Boeddinghaus J, Twerenbold R, Nestelberger T. et al. Clinical validation of a novel high-sensitivity cardiac troponin I assay for early diagnosis of acute myocardial infarction. Clin Chem 2018; 64: 1347-1360
• 9 McCarthy CP, Raber I, Chapman AR. et al. Myocardial injury in the era of high-sensitivity cardiac troponin assays: A practical approach for clinicians. JAMA Cardiol. 2019
• 10 Goodman SG, Steg PG, Eagle KA. et al. The diagnostic and prognostic impact of the redefinition of acute myocardial infarction: Lessons from the Global Registry of Acute Coronary Events (GRACE). Am Heart J 2006; 151: 654-660
• 11 Apple FS, Sandoval Y, Jaffe AS. et al. Cardiac troponin assays: Guide to understanding analytical characteristics and their impact on clinical care. Clin Chem 2017; 63: 73-81
• 12 Frankenstein L, Wu AH, Hallermayer K. et al. Biological variation and reference change value of high-sensitivity troponin T in healthy individuals during short and intermediate follow-up periods. Clin Chem 2011; 57: 1068-1071
• 13 Willeit P, Welsh P, Evans JDW. et al. High-sensitivity cardiac troponin concentration and risk of first-ever cardiovascular outcomes in 154 052 participants. J Am Coll Cardiol 2017; 70: 558-568
• 14 Blankenberg S, Salomaa V, Makarova N. et al. Troponin I and cardiovascular risk prediction in the general population: The BiomarCaRE consortium. Eur Heart J 2016; 37: 2428-2437
• 15 Seliger SL, Hong SN, Christenson RH. et al. High-sensitive cardiac troponin T as an early biochemical signature for clinical and subclinical heart failure: MESA (Multi-Ethnic Study of Atherosclerosis). Circulation 2017; 135: 1494-1505
• 16 Zhu K, Knuiman M, Divitini M. et al. High-sensitivity cardiac troponin I and risk of cardiovascular disease in an Australianpopulation-based cohort. Heart 2018; 104: 895-903
• 17 Welsh P, Preiss D, Shah ASV. et al. Comparison between high-sensitivity cardiac troponin T and cardiac troponin I in a large general population cohort. Clin Chem 2018; 64: 1607-1616
• 18 Rubini Gimenez M, Twerenbold R, Reichlin T. et al. Direct comparison of high-sensitivity-cardiac troponin I vs. T for the early diagnosis of acute myocardial infarction. Eur Heart J 2014; 35: 2303-2311
• 19 Hallen J, Johansen OE, Birkeland KI. et al. Determinants and prognostic implications of cardiac troponin T measured by a sensitive assay in type 2 diabetes mellitus. Cardiovasc Diabetol 2010; 9: 52
• 20 Festa A, D'Agostino R, Tracy RP. et al. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 2002; 51: 1131-1137
• 21 Kannel WB. Lipids, diabetes, and coronary heart disease: Insights from the Framingham Study. Am Heart J 1985; 110: 1100-1107
• 22 Balletshofer BM, Rittig K, Enderle MD. et al. Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance. Circulation 2000; 101: 1780-1784
• 23 Brohall G, Oden A, Fagerberg B. Carotid artery intima-media thickness in patients with Type 2 diabetes mellitus and impaired glucose tolerance: A systematic review. Diabet Med 2006; 23: 609-616
• 24 Lorenz MW, Markus HS, Bots ML. et al. Prediction of clinical cardiovascular events with carotid intima-media thickness: A systematic review and meta-analysis. Circulation 2007; 115: 459-467
• 25 Lorenz MW, Price JF, Robertson C. et al. Carotid intima-media thickness progression and risk of vascular events in people with diabetes: Results from the PROG-IMT collaboration. Diabetes Care 2015; 38: 1921-1929
• 26 Dallosso H, Yates T, Mani H. et al. Movement through Active Personalised engagement (MAP) - a self-management programme designed to promote physical activity in people with multimorbidity: study protocol for a randomised controlled trial. Trials 2018; 19: 576
• 27 Levey AS, Coresh J, Greene T. et al. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 2007; 53: 766-772
• 28 Touboul PJ, Hennerici MG, Meairs S. et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis 2012; 34: 290-296
• 29 Randrianarisoa E, Rietig R, Jacob S. et al. Normal values for intima-media thickness of the common carotid artery – an update following a novel risk factor profiling. Vasa 2015; 44: 444-450
• 30 Chambless LE, Folsom AR, Davis V. et al. Risk factors for progression of common carotid atherosclerosis: The Atherosclerosis Risk in Communities Study, 1987-1998. Am J Epidemiol 2002; 155: 38-47
• 31 O'Leary DH, Polak JF, Kronmal RA. et al. Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group. Stroke 1992; 23: 1752-1760
• 32 Mosca L, Benjamin EJ, Berra K. et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: A guideline from the american heart association. Circulation 2011; 123: 1243-1262
• 33 GBD 2013 Mortality and Causes of Death Collaborators Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385: 117-171
• 34 Maffei S, Guiducci L, Cugusi L. et al. Women-specific predictors of cardiovascular disease risk - new paradigms. Int J Cardiol. 2019
• 35 Yiu KH, Zhao CT, Chen Y. et al. Association of subclinical myocardial injury with arterial stiffness in patients with type 2 diabetes mellitus. Cardiovasc Diabetol 2013; 12: 94
• 36 Wagenknecht LE, D'Agostino RB, Haffner SM. et al. Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: The Insulin Resistance Atherosclerosis Study. Diabetes Care 1998; 21: 1812-1818
• 37 Temelkova-Kurktschiev TS, Koehler C, Leonhardt W. et al. Increased intimal-medial thickness in newly detected type 2 diabetes: Risk factors. Diabetes Care 1999; 22: 333-338
• 38 Kablak-Ziembicka A, Przewlocki T, Tracz W. et al. Gender differences in carotid intima-media thickness in patients with suspected coronary artery disease. Am J Cardiol 2005; 96: 1217-1222
• 39 Segre CA, Hueb W, Garcia RM. et al. Troponin in diabetic patients with and without chronic coronary artery disease. BMC Cardiovasc Disord 2015; 15: 72
• 40 Cavender MA, White WB, Jarolim P. et al. Serial Measurement of High-Sensitivity Troponin I and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus in the EXAMINE Trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care). Circulation 2017; 135: 1911-1921
• 41 Collinson PO, Heung YM, Gaze D. et al. Influence of population selection on the 99th percentile reference value for cardiac troponin assays. Clin Chem 2012; 58: 219-225
• 42 Apple FS, Simpson PA, Murakami MM. Defining the serum 99th percentile in a normal reference population measured by a high-sensitivity cardiac troponin I assay. Clin Biochem 2010; 43: 1034-1036
• 43 Guclu T, Bolat S, Senes M. et al. Relationship between high sensitivity troponins and estimated glomerular filtration rate. Clin Biochem 2016; 49: 467-471
• 44 Twerenbold R, Wildi K, Jaeger C. et al. Optimal cutoff levels of more sensitive cardiac troponin assays for the early diagnosis of myocardial infarction in patients with renal dysfunction. Circulation 2015; 131: 2041-2050
• 45 Artunc F, Haag S, Friedrich B. et al. Performance of a novel high sensitivity cardiac troponin I assay in asymptomatic hemodialysis patients - evidence for sex-specific differences. Clin Chem Lab Med 2019; 57: 1261-1270
• 46 Simon A, Megnien JL, Chironi G. The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol 2010; 30: 182-185