Heart Rate Variability and Heart Rate (page 1334)
Heart rate variability (HRV) was developed as a marker of cardiac autonomic tone and cardiovascular risk, attracting >17 000 publications on PubMed. Few of these acknowledge the dependent relationship between HRV and heart rate (HR). This means that differences in HRV measured at different HRs are often in part or in full attributable to the different HR at which they were measured. Articles that do acknowledge this relationship often make linear corrections for HR, which are inadequate because the relationship between HRV and HR is nonlinear. In this issue of Hypertension, Monfredi et al use their own data from in vivo records, Langendorff-perfused hearts and isolated single sinoatrial node cells, as well as data from a wide variety of other clinical and nonclinical HRV articles, to demonstrate that regardless of the conditions/species/cardiac preparation, there is a universal exponential decay-like relationship between HRV and HR. They develop 2 biophysical models to explore this, concluding that HRV differences between 2 steady states are primarily dependent on the differences in HR between these 2 states and cannot be used in any simple way to assess differences in cardiac autonomic activity. Their findings suggest that articles that have shown differences in HRV between ≥2 steady states at different HRs may need their conclusions revisited: this may have implications for other types of variability, including blood pressure variability.
Bioencapsulated Angiotensin-Con verting Enzyme 2/Angiotensin-(1-7) for Oral Pulmonary Hypertension Therapy (page 1248)
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by elevated blood pressure in the pulmonary arteries. Vasoconstriction, cellular proliferation, and a prothrombotic state result in increased resistance in the lungs leading to right ventricular dysfunction and failure. Restoration of the diminished angiotensin-converting enzyme 2/angiotensin-(1-7) (ACE2/Ang-(1-7)) axis through genetic overexpression or activation of ACE2 is effective against PAH and intravenous injections of recombinant ACE2 are progressing into human clinical trials. However, current protein drugs are not available for a majority of the global population because their production requires expensive fermenters, purification, cold storage, short shelf life, and sterile delivery methods. In addition, repetitive injections may require frequent hospital visits and affect patient compliance. In the current issue of Hypertension, Shenoy et al report a novel approach to oral delivery of ACE2 or Ang-(1-7), which were expressed and bioencapsulated in plant cells, that are protected from digestive acids/enzymes but are released in the gut after lyses of plant cells by commensal bacteria colonizing the gut. In this study, oral delivery of plant cells containing ACE2 or Ang-(1-7) significantly improved cardiopulmonary structure and functions in rats with monocrotaline-induced PAH in both prevention and reversal protocols. Not only was right ventricular systolic blood pressure decreased but the pulmonary blood flow was also improved. Interestingly, oral ACE2/Ang-(1-7) feeding restored right heart function and attenuated maladaptive remodeling in diseased animals. Thus, the study demonstrates that oral feeding of ACE2 or Ang-(1-7) is effective against PAH, and this strategy is ready for clinical trials with a view to producing affordable PAH therapeutics.
Diabetes Mellitus, Endothelium, and Cardiovascular Events (page 1299)
In the pathogenesis of cardiovascular events, interaction (ie, synergy) between risk factors has seldom been identified. From a clinical point of view, detection of interaction between risk factors is, however, important because this identifies key therapeutic targets: interventions aimed at such risk factors are potentially more efficacious than treatment of risk factors that do not interact. In this issue of Hypertension, van Sloten et al used prospective data of the Hoorn Study to evaluate the interaction between endothelial dysfunction, as measured by flow-mediated dilatation, and type 2 diabetes mellitus, impaired glucose metabolism and insulin resistance with regard to risk of cardiovascular events. The results of the study showed that endothelial dysfunction and type 2 diabetes mellitus, impaired glucose metabolism, or insulin resistance synergistically increase cardiovascular event risk. That is, individuals with type 2 diabetes mellitus, impaired glucose metabolism, or insulin resistance were found to be particularly sensitive to the adverse cardiovascular effects of endothelial dysfunction, in contrast to individuals with normal glucose metabolism or normal insulin sensitivity. Thereby, this study identifies endothelial dysfunction as a key therapeutic target for prevention of cardiovascular events in individuals with type 2 diabetes mellitus. In addition, the fact that an interaction was already present in individuals with impaired glucose metabolism, and insulin resistance identifies endothelial dysfunction as an early therapeutic target even before onset of type 2 diabetes mellitus.
- © 2014 American Heart Association, Inc.