High-sensitivity cardiac troponin T is associated with cognitive decline in older adults at high cardiovascular risk

Aims Cardiac troponin T (cTnT), measured with a high-sensitivity (hs) assay, is associated with cognitive decline, but the underlying mechanism is unknown. We investigated the association of hs-cTnT with cognitive function and decline, and studied whether this association was independent of cardiovascular diseases or risk factors, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Methods and results We studied 5407 participants (mean age 75.31 years) from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), who all had cardiovascular diseases or risk factors thereof. Participants with pre-existent advanced clinical heart failure were excluded. Hs-cTnT and NT-proBNP obtained after 6 months of follow-up were related with cognitive function, tested repeatedly during a mean follow-up of 3.2 years. Participants with higher hs-cTnT performed worse at baseline on Stroop test (mean baseline score (standard error (SE)) lowest vs highest third 65.91 (1.16) vs 69.40 (1.10) seconds, p < 0.001), Letter–Digit Coding test (23.35 (0.32) vs 22.40 (0.31) digits coded, p < 0.001), immediate Picture–Word Learning test (9.45 (0.09) vs 9.31 (0.08) pictures remembered, p = 0.002) and delayed Picture–Word Learning test (10.33 (0.12) vs 10.10 (0.12) pictures remembered, p = 0.013). Furthermore, participants with higher hs-cTnT had steeper decline on Stroop test (mean annual change (SE) lowest vs highest third 0.34 (0.12) vs 1.06 (0.12) seconds, p = 0.013), Letter–Digit Coding test (–0.29 (0.03) vs −0.46 (0.03) digits coded, p < 0.001), immediate Picture–Word Learning test (0.01 (0.01) vs −0.06 (0.01) pictures remembered, p < 0.001) and delayed Picture–Word Learning test (–0.03 (0.01) vs −0.12 (0.02) pictures remembered, p = 0.001). Associations were independent of cardiovascular diseases risk factors or Apolipoprotein E genotype. Further adjusting for NT-proBNP levels revealed the same results. Conclusions Higher levels of hs-cTnT associate with worse cognitive function and steeper cognitive decline in older adults independent of cardiovascular diseases, risk factors and NT-proBNP.

[1]  F. Neumann,et al.  High-sensitivity cardiac troponin for risk prediction in patients with and without coronary heart disease. , 2014, International journal of cardiology.

[2]  N. Sattar,et al.  N‐terminal pro–brain natriuretic peptide and cognitive decline in older adults at high cardiovascular risk , 2014, Annals of neurology.

[3]  C. Ballantyne,et al.  High-sensitivity cardiac troponin T and cognitive function and dementia risk: the atherosclerosis risk in communities study. , 2014, European heart journal.

[4]  P. Wolf,et al.  LOW CARDIAC INDEX IS ASSOCIATED WITH INCIDENT DEMENTIA AND ALZHEIMER'S DISEASE: THE FRAMINGHAM HEART STUDY , 2014, Alzheimer's & Dementia.

[5]  J. McMurray,et al.  Prognostic Effect of High-Sensitive Troponin T Assessment in Elderly Patients With Chronic Heart Failure: Results From the CORONA Trial , 2013, Circulation. Heart failure.

[6]  M. Fornage,et al.  Cardiovascular Biomarkers and Subclinical Brain Disease in the Atherosclerosis Risk in Communities Study , 2013, Stroke.

[7]  A. Go,et al.  Association of N-terminal pro-B-type natriuretic peptide with left ventricular structure and function in chronic kidney disease (from the Chronic Renal Insufficiency Cohort [CRIC]). , 2013, The American journal of cardiology.

[8]  A. Wimo,et al.  The global prevalence of dementia: A systematic review and metaanalysis , 2013, Alzheimer's & Dementia.

[9]  R. Takahashi,et al.  Endogenous Cardiac Troponin T Modulates Ca2+-Mediated Smooth Muscle Contraction , 2012, Scientific Reports.

[10]  Mehdi Farhoudi,et al.  Association of apolipoprotein E epsilon 4 allele with sporadic late onset Alzheimer`s disease. A meta-analysis. , 2012, Neurosciences.

[11]  S. Black,et al.  Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association , 2011, Stroke.

[12]  Alan S Maisel,et al.  Elevated natriuretic peptide levels and cognitive function in community-dwelling older adults. , 2011, The American journal of medicine.

[13]  Eric Boerwinkle,et al.  Cardiac Troponin T Measured by a Highly Sensitive Assay Predicts Coronary Heart Disease, Heart Failure, and Mortality in the Atherosclerosis Risk in Communities Study , 2011, Circulation.

[14]  L. Pantoni.  Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges , 2010, The Lancet Neurology.

[15]  R. Sulkava,et al.  B-type natriuretic peptide as a predictor of declining cognitive function and dementia—a cohort study of an elderly general population with a 5-year follow-up , 2010, Annals of medicine.

[16]  C. Gregorio,et al.  Expression of the fast twitch troponin complex, fTnT, fTnI and fTnC, in vascular smooth muscle. , 2008, Cell motility and the cytoskeleton.

[17]  J. Michel,et al.  Troponin T as a marker of differentiation revealed by proteomic analysis in renal arterioles , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  P. Macfarlane,et al.  Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial , 2002, The Lancet.

[19]  P. Macfarlane,et al.  Testing cognitive function in elderly populations: the PROSPER study , 2002, Journal of neurology, neurosurgery, and psychiatry.

[20]  M. Pahor,et al.  Hypotension and cognitive impairment , 2001, Neurology.

[21]  P. Macfarlane,et al.  The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk. , 1999, The American journal of cardiology.

[22]  R. Bernabei,et al.  Left ventricular dysfunction: a clue to cognitive impairment in older patients with heart failure , 1997, Journal of neurology, neurosurgery, and psychiatry.

[23]  S. Sadigh-Eteghad,et al.  Association of apolipoprotein E epsilon 4 allele with sporadic late onset Alzheimer's disease , 2012 .

[24]  P. Macfarlane,et al.  Pravastatin and cognitive function in the elderly. Results of the PROSPER study , 2009, Journal of Neurology.

[25]  H. Kulbertus,et al.  [The PROSPER Study (PROspective study of pravastatin in the elderly at risk)]. , 2002, Revue medicale de Liege.