Blood Pressure Monitoring and Atrial Fibrillation (p 110)
Strategies aiming at effective screening for atrial fibrillation (AF) are expected to contribute considerably in early AF detection and management and thereby efficient stroke prevention. Ambulatory blood pressure monitoring (ABPM) is currently proposed by several organizations as reference tool for confirming the diagnosis of hypertension and is increasingly used in clinical practice. A novel ABPM device with implemented algorithm for automated AF detection during each blood pressure measurement has been developed. This study assessed the diagnostic accuracy of this device for AF detection versus reference 24-hour Holter monitoring during routine 24-hour ABPM in elderly hypertensives. In ABPM reading-to-reading analysis, the diagnostic accuracy of this novel technology for AF detection seemed to be reasonable with high sensitivity and moderate specificity. A high frequency of AF false-positive ABPM readings was caused by excessive supraventricular ectopic activity, which, however, confers high risk for future AF. The receiver operating characteristics curve revealed that AF-positive readings at 26% during 24-hour ABPM had sensitivity 100% and specificity 85% for detecting paroxysmal AF (area under the curve, 0.91; P<0.01). These findings suggest that in elderly hypertensives a 24-hour ABPM recording with at least 26% of the readings suggesting AF indicates a high probability for AF diagnosis and should be regarded as an indication for performing 24-hour Holter monitoring.
Endothelial PPARγ and Vascular Aging (p 227)
Aging is the greatest risk factor for vascular disease and its clinical complications, but insight into mechanisms that control vascular aging, particularly within individual cells, is very limited. Our ability to slow the progression of vascular aging is limited in part by our poor understanding of determinants of these changes. The transcription factor PPARγ (peroxisome proliferator–activated receptor-γ) has protective vascular effects when activated pharmacologically. To gain new insight into this area, we used mice expressing dominant negative PPARγ in endothelial cells (E-V290M) to test the hypothesis that interference with endothelial PPARγ augments age-induced vascular dysfunction. Because of their clinical importance in relation to stroke and cognitive deficits, we studied carotid arteries. Based on comparisons of E-V290M with nontransgenic littermates, our findings suggest age-related oxidative stress, inflammation, senescence, and endothelial dysfunction are increased after genetic interference with PPARγ, implicating an essential role for this molecule and cell type in protecting against key aspects of vascular aging. Loss of these beneficial effects because of disease, genetic changes, or protein alterations has implications for the rate of progression and severity of vascular aging, other forms of vascular disease, and potentially, effectiveness of therapeutic approaches. For example, dietary caloric restriction delays aging in many experimental models. Interestingly, PPARγ is one of the molecules with the strongest caloric restriction mimetic activity.
Role of Endothelial BH4 in Vascular Remodeling (p 128)
Evidence from experimental and clinical studies have demonstrated that reduced tetrahydrobiopterin (BH4) bioavailability, an essential cofactor for NO synthase, is associated with endothelial cell dysfunction and abdominal aortic aneurysm formation in response to Ang (Angiotensin) II. However, it is unknown if there is a specific requirement for endothelial cell BH4 in modulating susceptibility to structural vascular disease and if loss of endothelial cell BH4 impacts on pathological vascular remodeling. In this issue of Hypertension, we use an endothelial cell-specific knockout mouse (Gch1fl/flTie2cre mice) to investigate the requirement for endothelial cell BH4 in the cardiovascular response to Ang II. Even at a subpressor Ang II dose (0.4 mg/kg per day), we observed hypertension and pathological remodeling of both conduit and resistance arteries in Gch1fl/flTie2cre mice which were associated with eNOS (endothelial NO synthase) uncoupling and increased aortic eNOS-derived H2O2 generation. These findings indicate that selective endothelial cell BH4 deficiency is sufficient to cause pathophysiological changes in the vessel wall, in both large conduit vessels and small resistance vessels. Thus, targeting endothelial cell redox function, exemplified by Gch1 and BH4 biosynthesis, is not only a rational therapeutic target for improving endothelial functional but is also able to modify structural and pathological remodeling in cardiovascular disease.
- © 2018 American Heart Association, Inc.