Biochemical markers of myocardial remodelling in hypertensive heart disease

Abstract

The intricate mechanisms responsible for the structural remodelling of the myocardium that facilitates the evolution to heart failure in hypertensive patients, namely in those with left ventricular hypertrophy, requires from clinicians the utilization of a multibiomarker approach for short-term and long-term stratification as well as prognostication of patients. Biochemical markers may also help to identify patients with no clinical evidence of hypertensive heart disease, and provide information about the need for more aggressive therapy during different stages of the disease, and potentially provide valuable biochemical data for the specialist. Although there is a continuous and complex interplay between biochemical and imaging markers, perhaps their use will also have the potential to modify the medical management of patients with hypertensive heart disease and therapeutic decision-making by tailoring a targeted therapy according to the predominant mechanism of myocardial remodelling. This article will review in brief the most relevant information on a panel of circulating molecules that may accomplish the criteria required to be considered as biochemical markers of the cardiomyocyte and non-cardiomyocyte structural changes that occur in the hypertensive myocardium.

A Translational Approach to Hypertensive Heart Disease

“…However, for a circulating molecule can be considered a biochemical marker of hypertensive myocardial remodeling, it must fulfill several criteria. 34 Until now, several molecules have been proposed as biochemical markers of hypertensive myocardial remodeling that accomplish these criteria. For instance, plasma concentration of CT-1 has been correlated with LVM in untreated hypertensive patients, 28 suggesting that plasma CT-1 may be a potential marker for the assessment of cardiomyocyte hypertrophy and LVH in hypertensive patients.…”

“…On the other hand, recent data suggest that some biochemical markers related to myocardial fibrosis (ie, serum carboxy-terminal propeptide of procollagen type I) or cardiomyocyte apoptosis (ie, plasma annexin A5) may provide information useful to assess these aspects of myocardial remodeling in hypertensive patients. 34 The common negative aspect of these methodologies is the high cost that would have to be made available to the large hypertensive populations internationally. Indeed, to address their economic impact is a major issue for national health systems, as is the necessity to make present-day advanced technology cost-effective.…”

Mitogen-Activated Protein Kinases as Biomarkers of Hypertension or Cardiac Pressure Overload

“…Several changes in myocardial structure characterize hypertensive or pressureoverload heart disease that induces myocardial remodeling (eg, enhanced cardiomyocyte growth, excessive cardiomyocyte necrosis/apoptosis, accumulation of interstitial and perivascular collagen fibers, or disruption of the endomysial and perimysial collagen network). 1 In the long term, these cellular changes, if untreated, will deteriorate left ventricular function and facilitate the development of heart failure.…”

“…Their results suggest the following: (1) in mice, ERK, JNK, and p38 activation in peripheral WBCs are closely correlated with pressure overload; (2) in patients, ERK activation in WBCs reflects the degree of hypertension control; and (3) leukocytes might represent important cellular targets to mirror cardiac signaling. 6 For a circulating molecule to be considered a biochemical marker of myocardial remodeling, and possibly of cardiac overload, some criteria have been proposed recently by the Gonzalez et al 1 The criteria are as follows: (1) a relationship between its expression in the myocardium and its blood concentration; (2) a positive gradient from its concentration in coronary sinus blood toward its concentration in peripheral vein blood, proving its main cardiac origin; (3) an association between its blood concentration with the cardiac structural and/or functional parameters reflecting the hallmarks of the myocardial changes under study 1 ; and (4) levels that vary in parallel with the changes in the above parameters induced by pharmacological treatment. In addition, its determination must be easy and reproducible, and the biochemical marker must have a good sensitivity and specificity to detect the pathology under study.…”

“…In addition, its determination must be easy and reproducible, and the biochemical marker must have a good sensitivity and specificity to detect the pathology under study. 1 In hypertensive patients, some new biomarkers are promising in terms of their clinical perspectives (Table).…”