Can emerging biomarkers of myocardial remodelling identify asymptomatic hypertensive patients at risk for diastolic dysfunction and diastolic heart failure?

Abstract

AimsHypertension is one of the main drivers of the heart failure (HF) epidemic. The aims of this study were to profile fibro-inflammatory biomarkers across stages of the hypertensive heart disease (HHD) spectrum and to examine whether particular biochemical profiles in asymptomatic patients identify a higher risk of evolution to HF. Methods and resultsThis was a cross-sectional observational study involving a population of 275 stable hypertensive patients divided into two different cohorts: Group 1, asymptomatic hypertension (AH) (n ¼ 94); Group 2, HF with preserved ejection fraction (n ¼ 181). Asymptomatic hypertension patients were further subdivided according to left atrial volume index ≥34 mL/ m 2 (n ¼ 30) and ,34 mL/m 2 (n ¼ 64). Study assays involved inflammatory markers [interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP1), and tumour necrosis factor a], collagen 1 and 3 metabolic markers [carboxy-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 3 (PIIINP), and carboxy-terminal telopeptide of collagen 1 (CITP)], extra-cellular matrix turnover markers [matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and tissue inhibitor of metalloproteinase 1 (TIMP1)], and the brain natriuretic peptide. Data were adjusted for age, sex, systolic blood pressure, and creatinine. Heart failure with preserved ejection fraction was associated with an increased inflammatory signal (IL6, IL8, and MCP1), an increased fibrotic signal (PIIINP and CITP), and an increased matrix turnover signal (MMP2 and MMP9). Alterations in MMP and TIMP enzymes were found to be significant indicators of greater degrees of asymptomatic left ventricular diastolic dysfunction. ConclusionThese data define varying fibro-inflammatory profiles throughout different stages of HHD. In particular, the observations on MMP9 and TIMP1 raise the possibility of earlier detection of those at risk of evolution to HF which may help focus effective preventative strategies.--

The Role of Matrix Metalloproteinases 2 and 9 in Vascular and Ventricular Remodelling in Patients with Heart Failure with Preserved Ejection Fraction

“…Several studies show that changes in serum levels of MMP-2 and MMP-9 are associated with aging [ 6 ], arterial and ventricular stiffening [ 7 ] in patients with arterial hypertension [ [8][9][10][11][12][13][14] and patients with heart failure with preserved ejection fraction [15][16][17]. Their role in the evaluation of vascular and ventricular remodelling and determining the prognosis of the patient is still controversial.…”

Impact of Comorbidities on Myocardial Remodeling and Dysfunction In Heart Failure with Preserved Ejection Fraction

“…Markers of inflammation (urinary albumin, CRP, TNF-α, and TGF-β were independently associated with asymptomatic diastolic dysfunction [100]. High circulating IL6, TNF-α, IL8 and MCP1 were detected in a cross-sectional study of 275 stable hypertensive patients with or without HFpEF [48]. In salt sensitive hypertension, high salt intake leads to systemic oxidative stress [101] possibly because of renal production of proinflammatory cytokines [102].…”

“…In an endomyocardial biopsy study, when compared with controls, HFpEF patients had increased inflammatory cell transforming growth factor (TGF-β) expression, which induces transdifferentiation of fibroblasts into myofibroblasts, with increased production of collagen and decreased expression of matrix metalloproteinase type 1 (MMP1), whereas both myocardial collagen and the amount of inflammatory cells correlated with diastolic LV dysfunction [40]. As compared with asymptomatic hypertensives, HFpEF patients had increased circulating biomarkers of inflammation (interleukin 6 (IL6), IL8, monocyte chemoattractant protein 1 (MCP1), of collagen metabolism (aminoterminal propeptide of collagen III, carboxyterminal telopeptide of collagen I), and of ECM turnover (MMP2 and MMP9) [48]. In addition, MMP9, tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), and the ratio of MMP9/TIMP1 correctly identified patients with a high left atrial volume index, which reflects chronic diastolic LV dysfunction [48].…”

“…As compared with asymptomatic hypertensives, HFpEF patients had increased circulating biomarkers of inflammation (interleukin 6 (IL6), IL8, monocyte chemoattractant protein 1 (MCP1), of collagen metabolism (aminoterminal propeptide of collagen III, carboxyterminal telopeptide of collagen I), and of ECM turnover (MMP2 and MMP9) [48]. In addition, MMP9, tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), and the ratio of MMP9/TIMP1 correctly identified patients with a high left atrial volume index, which reflects chronic diastolic LV dysfunction [48]. Moreover, the Health ABC study reported inflammatory biomarkers such as IL6 and tumor necrosis factor α (TNF-α) to be strongly associated with incident HFpEF, but not incident HFrEF in elderly patients [49].…”

Lipids, Blood Pressure, Kidney-what was New in 2012?

“…Therefore, it is important to establish a panel of diagnostic tests in patients with hypertension to enable the early detection of abnormalities before the occurrence of symptoms and thus allow the implementation of optimal treatment [64,84]. Elevations in inflammatory markers, not observed in isolated hypertension, become evident in the presence of target organ damage [109][110][111][112]. Raised levels of high-sensitivity CRP (hs-CRP) and myeloperoxidase (MPO) have been suggested as markers of HF in hypertensive patients [113].…”