Targeting hypertensive myocardial fibrosis

In normal myocardium, myocytes represent only one-third of all cells, with the remaining two-thirds including fibroblasts and small cellular populations. While several weeks post partum the myocyte count stops increasing, the connective tissue cell count does not. In the early phases of arterial hypertension, adaptive left ventricular (LV) hypertrophy (LVH) is characterised by the growth of cardiac myocytes, which may or may not be accompanied by other alterations in tissue structure. In hypertensive heart disease, however, complex changes in myocardial composition occur, with a disproportionate involvement of noncardiomyocyte cells accounting for a pathological remodelling of tissue structure (pathological hypertrophy). Myocardial fibrosis is the result of both haemodynamic and nonhaemodynamic factors playing a synergistic role and reflects the loss of the physiological reciprocal regulation between stimulatory and inhibitory factors acting on the turnover of fibrillar collagen. Cardiac biopsy is the gold standard for assessing myocardial fibrosis; in the last decades different non-invasive approaches have been developed and validated to detect and follow-up cardiac fibrosis, including biochemical markers of collagen synthesis and degradation, cardiac hormones and ultrasonographic procedures. Due to the clinical implications of myocardial fibrosis and pathological LVH, it is of great interest to ascertain the effect of antihypertensive agents on cardiac structure: the optimal treatment of hypertensive patients should target a parallel decrease in cardiac mass and fibrosis. Preliminary evidence suggests that not all antihypertensive drugs affect fibrosis to the same extent: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) appear particularly effective, in contrast to β-blockers and diuretics. Finally, the impact of fibrosis and its regression on subsequent cardiovascular events when compared with LV mass and its reduction remain to be investigated.