Renal Resistive Index in Kidney Disease (page 382)
Clinical practice guidelines recommend the use of estimated glomerular filtration rate and albuminuria to assess the underlying cardiovascular and mortality risk in chronic kidney disease (CKD). In recent years, there has been a movement in the nephrology field to identify novel risk markers other than estimated glomerular filtration rate and albuminuria in predicting these outcomes. Renal resistive index (RRI), a noninvasive measure of intrarenal hemodynamics obtained from renal Doppler study, provides prognostic information in patients with hypertension. In this issue of Hypertension, Toledo et al report that RRI data obtained from a renal Doppler study (performed for a specific indication) can serve as a useful tool to predict mortality in patients with CKD who did not have clinically significant renal artery stenosis. They found that an elevated RRI of ≥0.70 is associated with higher mortality in hypertensive patients with CKD after accounting for other significant risk factors (Figure). Interestingly, the association was more pronounced among younger patients and those with stage 3 CKD. This suggests the utility of RRI as a risk marker in a population who have higher probability of dying because of cardiovascular disease rather than reaching dialysis. These results provide a framework for future prospective studies in exploring the role of RRI in identifying high-risk CKD patients who may benefit from early interventions.
Angiotensin-(1–7) Mechanisms Against Deoxycorticosterone Acetate Dysfunction (page 389)
Diastolic dysfunction is a common entity in hypertensive patients. To date, there is no proven therapy for diastolic dysfunction, highlighting the need for effective therapies. Mineralocorticoids have been implicated in the pathogenesis of diastolic dysfunction. On the contrary, preclinical data have shown evidence that angiotensin (Ang)-(1–7), a biologically active component of the renin–angiotensin system, effectively prevents cardiac remodeling induced by excessive mineralocorticoid receptor stimulation. These findings suggest that Ang-(1–7) could be an important therapeutic strategy to reduce pathology associated with increased mineralocorticoid activity. However, in some studies cardioprotection was accomplished in a background of reduced blood pressure, raising the question of whether Ang-(1–7)’s beneficial action was a consequence of attenuated blood pressure. In this issue, Almeida et al addressed this critical question by dissociating the blood pressure component of Ang-(1–7) from its cardioprotective effects in a model of increased mineralocorticoid receptor stimulation induced by deoxycorticosterone acetate treatment. Almeida et al reported that Ang-(1–7) slows the development of hypertensive disease by preventing the transition from left ventricular hypertrophy to diastolic dysfunction independently from its blood pressure–lowering effects. Importantly, this cardioprotective signaling is mediated by the activation of pathways involved in Ca2+ handling, hypertrophy, and survival in cardiomyocytes. This work provides important mechanistic input that could help to develop therapeutic strategies based on the use of Ang-(1–7) or Ang-(1–7)–like compounds alone or in combination with other drugs for patients with hypertensive disease.
Obesity Exerts Myocardial Mitochondrial Dysfunction (page 430)
Obesity and hypertension are major risk factors for cardiovascular diseases, and their increasingly common coexistence accounts for an upsurge in adverse cardiac events, yet the mechanisms are poorly understood. In addition to shared pathogenic pathways such as inflammation and oxidative stress, excessive nutrient substrates imposed in obesity may decrease energy production, as burdened mitochondria experience stress and develop dysfunction, as also observed in hypertension-induced left ventricular (LV) hypertrophy. Would concurrent obesity impact cardiac mitochondrial integrity in hypertension? In this issue of Hypertension, Zhang et al report that obesity superimposed on hypertension exacerbates LV diastolic dysfunction and myocardial fibrosis, accompanied by a wide range of mitochondrial injuries involving their quantity, quality, and dynamics in the LV myocardium. A sixteen-week high-fat diet with concomitant 4-week renovascular hypertension elicited in obesity-prone Ossabaw pigs significant reductions in LV myocardial mitochondrial proteins and deoxyribonucleic acid content (Figure), as well as biogenic regulators. The synergistic or additive effects of obesity and hypertension also decreased mitochondrial respiratory chain complex activity and amplified their self-degradation. These mitochondrial changes were correlated with myocardial fibrosis. Given that these observations were made at an early stage of LV hypertrophy, they underscore the importance of mitochondrial homeostasis in maintenance of myocardial health. Further investigations are needed to increase our understanding of cardiac mitochondrial metabolic dynamics and their potential role as therapeutic targets in cardiac dysfunction.
- © 2015 American Heart Association, Inc.