Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk

Abstract

The search for biomarkers of hypertension and diabetes-induced damage to multiple target organs is a priority. We analyzed the correlation between plasma cardiotrophin-1 (CT-1), a chemokine that participates in cardiovascular remodeling and organ fibrosis, and a wide range of parameters currently used to diagnose morphological and functional progressive injury in left ventricle, arteries, and kidneys of diabetic and hypertensive patients, in order to validate plasma levels of CT-1 as clinical biomarker.This is an observational study with 93 type 2-diabetic patients, 209 hypertensive patients, and 82 healthy controls in which we assessed the following parameters: plasma CT-1, basal glycaemia, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), left ventricular hypertrophy (LVH by electrocardiographic indexes), peripheral vascular disease (by pulse wave velocity—PWV, carotid intima-media thickness—C-IMT, and ankle-brachial index—ABI), and renal impairment (by microalbuminuria, albumin/creatinine urinary ratio, plasma creatinine concentrations, and glomerular filtration rate).Hypertensive or diabetic patients have higher plasma CT-1 than control patients. CT-1 positively correlates with basal glycaemia, SBP, DBP, PP, LVH, arterial damage (increased IMT, decreased ABI), and early renal damage (microalbuminuria, elevated albumin/creatinine ratio). CT-1 also correlates with increased 10-year cardiovascular risk. Multiple linear regression analysis confirmed that CT-1 was associated with arterial injury assessed by PWV, IMT, ABI, and cardiac damage evaluated by Cornell voltage duration product.Increases in plasma CT-1 are strongly related to the intensity of several parameters associated to target organ damage supporting further investigation of its diagnostic capacity as single biomarker of cardiovascular injury and risk and, possibly, of subclinical renal damage.

Cardiotrophin‐1 opposes renal fibrosis in mice: Potential prevention of chronic kidney disease

“…The increased CT‐1 expression observed after UUO is congruent with CT‐1 acting as an endogenous defence mechanism activated to repair or counteract tubular injury, providing a protective effect against renal damage and fibrosis. Congruently with this, we previously reported that plasma levels of CT‐1 correlate with early renal damage (ie as evidenced by microalbuminuria and elevated albumin/creatinine ratio) in hypertensive and diabetic patients . All in all, these findings propose CT‐1 as a protective tissue barrier, as a potential biomarker of renal repair and, by extension, as a surrogate marker of renal fibrosis.…”

“…Congruently with this, we previously reported that plasma levels of CT-1 correlate with early renal damage (ie as evidenced by microalbuminuria and elevated albumin/creatinine ratio) in hypertensive and diabetic patients. 38 All in all, these findings propose CT-1 as a protective tissue barrier, as a potential biomarker of renal repair and, by extension, as a surrogate marker of renal fibrosis.…”

N-acetyl Cysteine Can Blunt Metabolic and Cardiovascular Effects via Down-regulation of Cardiotrophin-1 in Rat Model of Fructose-induced Metabolic Syndrome

“…In a study done by Gkaliagkousi et al [78], CT-1 levels was positively correlated with blood pressure and the indices of arterial stiffness. In another study, positive correlation between plasma CT-1 and basal glycemia, SBP and DBP were reported [79]. Also, they observed a positive association between CT-1 and arterial damage (increase intima-media thickness).…”

G protein‐coupled receptor kinase‐2: A potential biomarker for early diabetic cardiomyopathy

“…The present study complemented a growing list of candidate biomarkers for DCM, such as NT‐proBNP, ANP, Cardiotrophin‐1, IGFBP‐7, and GRK2. Different from the elevated GRK2 expression, elevated NT‐proBNP and ANP levels suggest the advanced stage of cardiomyopathy, especially for heart failure; plasma cardiotrophin‐1 expression elevated in diabetes patients with cardiac hypertrophy and systolic dysfunction; and IGFBP‐7 expression was revealed to be related to insulin resistant, cardiac hypertrophy, and cardiac fibrosis . These biomarkers represent several putative mechanistic pathways underlying DCM progression.…”