Cognitive Decline in Incident Hypertension (page 245)
Hypertension is considered a major risk factor for cognitive decline and dementia. Epidemiological studies have shown that, in existing hypertension, the decline is more pronounced in midlife than late life, suggesting time windows of increased risk during the life course. Managing blood pressure at an early age, hence, seems desirable for promoting healthy late-life cognitive functioning. In addition, timely intervention might also be important, but how cognitive changes evolve in incident hypertension is largely unknown. In this issue of Hypertension, results from the Maastricht Ageing Study on 1805 adults confirm earlier findings of accelerated decline in midlife hypertension. In those with existing hypertension, decline was most widespread in those receiving antihypertensive medication but still having high blood pressure (uncontrolled hypertension). In the 352 individuals who developed incident hypertension during the 12-year follow-up period, no decline occurred in the years preceding the diagnosis of hypertension, but decline evolved gradually thereafter. In this group, changes were generally modest and differed across treatment groups. Again, more widespread deficits were observed in those with poorly controlled blood pressure. This gradual evolution of cognitive changes in incident hypertension could mirror underlying atherosclerotic changes. Findings suggest that adequate management of blood pressure might delay or even prevent onset and progression of cognitive decline in midlife.
Chemokine Receptor 7 and Endothelial Progenitor Cell Functions in Hypertension (page 383)
Bone marrow–derived circulating endothelial progenitor cells (EPCs) have been used successfully to enhance re-endothelialization after arterial injury. Cardiovascular risk factors negatively influence EPC number and function, whereas medication and healthy lifestyle interventions contribute to maintenance of endothelial homeostasis at least in part via upregulation of EPCs. Dysfunction of EPCs is responsible for impaired endothelial repair capacity in patients with hypertension. Chemokine receptor seven (CXCR7) plays an essential role in the vascular system and binds to SDF-1 (stromal-derived factor 1) with higher affinity than CXCR4. Therefore, the deep insight into the role of CXCR7 signaling in the modulation of re-endothelialization capacity of EPCs may be of important clinical implication for our further understanding of the pathogenesis of EPC dysfunction in hypertension and developing a novel potential therapeutic target. Compared with healthy subjects, CXCR7 expression of EPCs from hypertensive patients was significantly reduced. Meanwhile, the phosphorylation of p38 mitogen-activated protein kinase, a downstream signaling of CXCR7, was elevated, which increased cleaved casepase-3 level of EPCs. CXCR7 gene transfer and lercanidipine, a dihydropyridine calcium channel antagonist, facilitated EPC-mediated improvement of endothelial repair capacity in patients with hypertension through regulating CXCR7/p38 mitogen-activated protein kinase/casepase-3 signaling pathway, which was paralleled to EPC functional upregulation of in vitro adhesion, antiapoptosis activities. These findings demonstrate the beneficial influence of CXCR7 of EPCs in endothelial repair mechanisms and its potentially protective and therapeutic role in hypertension. Upregulation of CXCR7 expression induced by gene transfer or lercanidipine treatment may be a novel therapeutic target for increased endothelial repair capacity in hypertension.
Fat Diet Induces Sympathoexcitation in Offspring (page 338)
In Western countries, 2 in 3 babies are born to overweight or obese mothers and are prone to developing obesity-related hypertension. This developmentally programmed obesity-related hypertension may differ in pathogenesis to adult-acquired obesity hypertension thereby requiring different management strategies. Therefore, we need to understand the mechanisms by which maternal obesity predisposes obesity-related hypertension in offspring. In this issue of Hypertension, we show that rabbit offspring from dams fed a high-fat diet during the fetal and suckling periods have higher blood pressure, heart rate, and renal sympathetic nerve activity as adults even when they are fed a low fat, calorie-controlled diet from weaning. Offspring also show enhanced sympathoexcitatory effects to centrally administered leptin but are resistant to leptin’s appetite-suppressing actions. This suggests that specific activation of sympathetic responses to leptin in the central nervous system occurs with only minor elevations of visceral fat accumulation compared with the effect of fat-feeding in adulthood. The study not only highlights how maternal nutrition can adversely affect cardiovascular risk factors in the next generation but also suggests that the intergenerational effects may have a multiplying effect by reducing the threshold for the development of hypertension in the face of obesity. Furthermore, if these findings translate to humans, the lack of appetite suppressant actions of leptin in programmed offspring may further increase the incidence of obesity in the community through this intergenerational mechanism.
- © 2013 American Heart Association, Inc.