Apoptosis in hypertensive heart disease: a clinical approach

PURPOSE OF REVIEW: It is widely accepted that there are two principal forms of cell death, namely, necrosis and apoptosis. According to the classical view, necrosis is the major mechanism of cardiomyocyte death in cardiac diseases. RECENT DEVELOPMENTS: In the past few years observations have been made showing that cardiomyocyte apoptosis occurs in diverse conditions including hypertensive heart disease, and that apoptosis may be a contributing cause of loss and functional abnormalities of cardiomyocytes in this condition. SUMMARY: This review will summarize recent evidence demonstrating the potential contribution of cardiomyocyte apoptosis to heart failure in hypertensive patients. In addition, some strategies aimed to detect and prevent apoptosis of cardiomyocytes will be considered.     

Biochemical markers of myocardial remodelling in hypertensive heart disease

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.     

New targets to treat the structural remodeling of the myocardium

Classical therapy of heart failure is based on treatment of its pre-disposing/triggering factors and of the neurohumoral activation secondary to the deterioration of cardiac function. A new view is emerging that proposes the direct intervention on the pathological structural remodeling of the myocardium as part of heart failure therapy. In fact, in conditions of chronic injury, the cardiomyocytic and the noncardiomyocytic components of the myocardium undergo a series of structural lesions (i.e., cardiomyocyte growth and death, inflammation, alterations of collagen matrix, and microvascular rarefaction) that are governed by a complex interplay of mechanisms. Our increasing knowledge of the role of these mechanisms in remodeling enables us not only to better understand how our more successful therapies work but also to explore novel therapies for the future. In this paper, we will examine recent insights from experimental and pilot clinical studies that have provided new targets for interventions to prevent or reverse inflammation, alterations of collagen matrix, and cardiomyocyte death.     

Hypertensive left ventricular hypertrophy risk: beyond adaptive cardiomyocytic hypertrophy

The heart is a remarkably adaptive organ, capable of increasing its minute output and overcoming short-term or prolonged pressure overload. The structural response, in addition to the foregoing functional demands, is that of myocardial hypertrophy. Then, why should an adaptive response increase cardiovascular risk in hypertensive patients with left ventricular hypertrophy (LVH)? Evidence shows that the functional performance of hypertrophied cardiomyocytes is impaired, and that additional alterations develop in cardiomyocytes themselves, the extracellular matrix and the intramyocardial vasculature, leading to myocardial remodelling and providing the basis for the adverse prognosis associated with pathological LVH in hypertensive patients (i.e., hypertensive heart disease, HHD). As molecular information accumulates, the pathophysiological understanding and the clinical approach to HHD are changing. The time has come to develop novel diagnostic and therapeutic strategies aimed at improving the prognosis of HHD on the basis of reversing or even preventing the aforementioned changes in the ventricular myocardium.     

Review of the renal endpoints used in cardiovascular safety clinical trials in type 2 diabetes mellitus patients and their importance in primary care

Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes mellitus (T2DM). Furthermore, CKD confers a considerable increase in the risk of cardiovascular (CV) morbidity and mortality. In line with the need to improve knowledge in this field, this article aims to describe the renal endpoints used in the different cardiovascular outcome trials (CVOTs). The objective is to better know the renal variables used in the different CVOTs in order to optimize the implementation of advances in the prevention of progressive diabetic kidney disease in patients with T2DM in clinical practice.     

Conservative treatment of severe defecatory urgency and fecal incontinence: minor strategies with major impact

Background

Bowel disturbances have been identified as the most important risk factor for fecal incontinence (FI). However, few studies have evaluated the impact of fiber supplementation. Our aim was to assess the correlation between the improvement in stool consistency by fiber supplementation and the changes in urgency and number of FI episodes and in the QoL of patients with FI.

Methods

Eighty-three patients who came to our institution with FI and/or fecal urgency associated with loose stools or diarrhea were prospectively included in the study The intervention included dietary advice and methylcellulose 500 mg every 8 h for 6 weeks. All assessments were carried out at baseline and 6 weeks after the start of the intervention, and included a Bristol Stool Scale, a 3-week bowel diary, the St Mark’s score, the Fecal Incontinence Quality of Life scale (FIQL) and a bowel satisfaction score.

Results

Sixty-one patients completed the study. At baseline 50 reported episodes of urge incontinence, while 11 did not report FI episodes because they rarely left home to avoid leakage. The Bristol score improved to normal stools in 65.6% of patients after treatment. Bowel diaries showed a statistically significant reduction in the number of bowel movements, urge episodes, urge fecal incontinence episodes and soiling per week. The St Mark’s score and the bowel satisfaction score significantly improved after methylcellulose and overall deferment time also increased. FIQL significantly improved in two subdomains (lifestyle, coping/behavior). Thirty-one patients (51.7%) were discharged with methylcellulose as the only treatment.

Conclusions

FI may significantly improve with methylcellulose in selected cases. Assessment of fecal consistency and initial treatment with methylcellulose could be started at primary care level to reduce the need for specialist referral.