Ambulatory Blood Pressure Control With Bedtime Aspirin Administration in Subjects With Prehypertension

Abstract

According to the Seventh Report of the Joint National Committee, 1 prehypertension is a designation chosen to identify individuals at high risk of developing hypertension and suffering cardiovascular events. 2,3 In a recent study, Hansen et al. 4 found that progression from optimal or normal blood pressure (BP) to high-normal BP or hypertension carries nearly the same risk for cardiovascular events as sustained high-normal BP or hypertension. The Trial of Preventing Hypertension study 5 has suggested that treating prehypertension with an angiotensin-receptor blocker might be effective in slowing the rate of progression to hypertension. Similar conclusions have been recently reported for the angiotensinconverting enzyme inhibitor ramipril. 6 Several criticisms, however, have been raised regarding the design, results, and conclusions derived from the Trial of Preventing Hypertension and its recommendation for pharmacologic treatment of prehypertension. 7,8 Moreover, current guidelines 1,9 indicate that individuals who are prehypertensive are not candidates for drug therapy on the basis of their level of BP and they should be advised to practice lifestyle modification in order to reduce their risk of developing hypertension in the future. Because subjects at low or moderate cardiovascular risk show poor compliance to lifestyle modification, 10 other low-cost and effective ways of controlling BP in prehypertension may be clinically relevant.Acetylsalicylic acid (aspirin, ASA) is a nonsteroidal antiinflammatory drug with demonstrated inhibitory effects on cyclooxygenases, responsible for arachidonic acid metabolism and prostaglandin production. 11 Previous studies have demonstrated that ASA is a potent antioxidative agent that markedly reduces vascular production of superoxide in normotensive and hypertensive rats. 12 In addition, ASA was found to prevent angiotensin II-induced hypertension and cardiovascular hypertrophy in rats, mainly through its antioxidative properties in preventing the generation of superoxide. 13 Moreover, recent results have demonstrated that ASA induces nitric oxide (NO) release from vascular endothelium. 14,15 This effect appears to be due to a direct acetylation of the endothelial NO synthase protein.Most relevant, previous clinical trials demonstrate effects of ASA that depend on the daily time of administration. Thus, the Background Aspirin has been found to prevent angiotensin II-induced hypertension and to induce nitric oxide (NO) release from vascular endothelium. Low-dose aspirin has also been shown to reduce blood pressure (BP) when administered at bedtime, as opposed to upon awakening, in untreated hypertensive patients and highrisk pregnant women. Accordingly, we investigated the effects on ambulatory BP of aspirin administered at different times of the day in prehypertension.

Antihypertensive Effects of Aspirin: What is the Evidence?

“…In fact, successful PROBE trials, such as the Hypertension Optimal Treatment (HOT) trial [25], have included a placebo arm and robust methods to preserve the masking of the treatments. Although a recent meta-analysis of PROBE trials suggests that double blinding may not be needed in trials of antihypertensive drugs based on ABPM [24], it is worth noting that investigators involved in decisions about ABPM data quality and analysis in those trials were blinded to treatment assignment and (contrary to the trials of Hermida et al [14,15,16•]) had no easy way to discover the assignment. Moreover, ABPM removes observer bias and expectation but not regression to the mean and participantrelated factors that contribute to the placebo effect [26].…”

Low-Dose Aspirin for Prevention of Cardiovascular Risk in Bereavement: Results from a Feasibility Study

“…It targets the main cardiovascular risk factors during bereavement, is inexpensive, is widely available, does not require a prescription, and is feasible in other short-term interventions. Low-dose aspirin is widely used for its antiplatelet effect, has anti-inflammatory properties, and positively influences depressed mood [4], HRV [5], and blood pressure [6].To investigate aspirin as a feasible preventive intervention, acutely bereaved participants (n = 10) were recruited on average within 30 days (SD = 14.67) of the death of their spouse; nonbereaved controls (n = 12) were also recruited. We assessed hemodynamic markers (blood pressure, heart rate, HRV) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CES-D) during 2 laboratory visits.…”

Relationship Between Endothelial Functions and Acetylsalicylic Acid Resistance in Newly Diagnosed Hypertensive Patients

“…43 Hermida et al showed that low-dose ASA (100 mg) had a favorable effect on blood pressure of patients in a study consisting of 244 prehypertension patients. 44 Recent studies have also demonstrated that ASA induces NO release from vascular endothelium. This effect appears to be due to a direct acetylation of the endothelial NO synthase protein.…”

“…This effect appears to be due to a direct acetylation of the endothelial NO synthase protein. 44 Systemic inflammation impairs endothelium-dependent dilatation in humans and provides direct evidence that pretreatment with an anti-inflammatory dose of aspirin protects from this endothelial dysfunction. This vasculoprotective effect of aspirin does not seem to be attributable to inhibition of vascular constrictor prostanoid synthesis, because locally infused aspirin did not restore endothelial function in vaccinated subjects.…”