Adrienne S. Zion

Estrogen replacement, vascular distensibility, and blood pressures in postmenopausal women.

The pathogenesis of blood pressure (BP) rise in aging women remains unexplained, and one of the many incriminating factors may include abnormalities in arteriolar resistance vessels. The aim of this study was to determine the effects of unopposed estrogen on arteriolar distensibility, baroreceptor sensitivity (BRS), BP changes, and rate-pressure product (RPP). We tested the hypotheses that estrogen replacement therapy (ERT) enhances arteriolar distensibility and ameliorates BRS, which leads to decreases in BP and RPP. Postmenopausal women participated in a single-blind crossover study; the participants of this study, after baseline measurements, were randomly assigned to receive estrogen (ERT) or a drug-free treatment with a 6-wk washout period between treatments. The single-blind design was instituted because subjects become unblinded due to physiological changes (i.e., fluid shifts, weight gain, and secretory changes) associated with estrogen intake. However, investigators and technicians involved in data collection and analyses remained blind. After each treatment, subjects performed identical autonomic tests, during which electrocardiograms, beat-by-beat BPs, and respiration were recorded. The area under the dicrotic notch of the BP wave was used as an index of arteriolar distensibility. The magnitude of the reflex bradycardia after a precipitous rise in BP was used to determine BRS. Power spectral analysis of heart rate variability was used to assess autonomic activity. BPs were recorded from resistance vessels in the finger using a beat-by-beat photoplethysmographic device. RPP, a noninvasive marker of myocardial oxygen consumption, was calculated. Repeated-measures analyses of variance revealed a significantly enhanced arteriolar distensibility and BRS after ERT (P < 0.05). A trend of a lower sympathovagal balance at rest was observed after ERT, however, this trend did not reach statistical significance (P = 0.061) compared with the other treatments. The above autonomic changes produced significantly lower systolic and diastolic BP changes and RPPs (P < 0.05) at rest and during isometric exercise. We conclude that short-term unopposed ERT favorably enhances arteriolar distensibility, BRS, and hemodynamic parameters in postmenopausal women. These findings have clinical implications in the goals for treating cardiovascular risk factors in aging women.The pathogenesis of blood pressure (BP) rise in aging women remains unexplained, and one of the many incriminating factors may include abnormalities in arteriolar resistance vessels. The aim of this study was to determine the effects of unopposed estrogen on arteriolar distensibility, baroreceptor sensitivity (BRS), BP changes, and rate-pressure product (RPP). We tested the hypotheses that estrogen replacement therapy (ERT) enhances arteriolar distensibility and ameliorates BRS, which leads to decreases in BP and RPP. Postmenopausal women participated in a single-blind crossover study; the participants of this study, after baseline measurements, were randomly assigned to receive estrogen (ERT) or a drug-free treatment with a 6-wk washout period between treatments. The single-blind design was instituted because subjects become unblinded due to physiological changes (i.e., fluid shifts, weight gain, and secretory changes) associated with estrogen intake. However, investigators and technicians involved in data collection and analyses remained blind. After each treatment, subjects performed identical autonomic tests, during which electrocardiograms, beat-by-beat BPs, and respiration were recorded. The area under the dicrotic notch of the BP wave was used as an index of arteriolar distensibility. The magnitude of the reflex bradycardia after a precipitous rise in BP was used to determine BRS. Power spectral analysis of heart rate variability was used to assess autonomic activity. BPs were recorded from resistance vessels in the finger using a beat-by-beat photoplethysmographic device. RPP, a noninvasive marker of myocardial oxygen consumption, was calculated. Repeated-measures analyses of variance revealed a significantly enhanced arteriolar distensibility and BRS after ERT ( P < 0.05). A trend of a lower sympathovagal balance at rest was observed after ERT; however, this trend did not reach statistical significance ( P = 0.061) compared with the other treatments. The above autonomic changes produced significantly lower systolic and diastolic BP changes and RPPs ( P < 0.05) at rest and during isometric exercise. We conclude that short-term unopposed ERT favorably enhances arteriolar distensibility, BRS, and hemodynamic parameters in postmenopausal women. These findings have clinical implications in the goals for treating cardiovascular risk factors in aging women.

Evaluation of blood pressure and baroreflex sensitivity by radial artery tonometry versus finger arteriolar photoplethysmography

BACKGROUND Published normative data of noninvasive blood pressures (BPs) and autonomic modulations have been primarily derived from the finger arteriole using the Finapres (Ohmeda Co., Englewood, CO), a device that is no longer manufactured. Currently, beat-to-beat BP are obtained from the radial artery using the Colin tonometer. METHODS We compared BP and autonomic parameters in a crossover design between the two devices in 29 subjects during seated rest and a 0.1-Hz breathing protocol. In addition, we tested whether finger arteriolar BP differences were due to pressure changes exerted by the radial tonometer. RESULTS Uniformly, BP measured at the radial artery were significantly higher than those from the finger arteriole. Radial BP (106 +/- 19.5 mm Hg) were higher than finger arteriolar BP (95.8 +/- 13.7 mm Hg) (P <.005). Tonometric baroreflex sensitivity (BRS) (24.0 +/- 18 msec/mm Hg) was higher compared to photoplethysmographic BRS (12.0 +/- 7.7 msec/mm Hg; P <.0003). Systolic BP (radial artery) (115 +/- 25 mm Hg) were higher compared to finger arteriolar BP (97.7 +/- 19 mm Hg; P <.0025) during breathing, as was BRS (25.9 +/- 11.6 msec/mm Hg v 21.5 +/- 11.6 msec/mm Hg; P <.05). Differences in the low frequency systolic BP (LF(SBP)), representative of sympathetic vasomotor modulation, between the two methods, whether absolute, normalized, or log-transformed were not observed. CONCLUSIONS There were no differences in arteriolar BP values in the presence or absence of radial artery tonometric pressure. These findings indicate that differences exist in systolic BP and BRS using the tonometer (radial artery) versus the Finapres (Ohmeda Co.) (finger arteriole). Furthermore, these differences are not due to pressure exerted by the radial artery tonometer that supplies blood to the finger arteriole.

Mechanoreceptors and autonomic responses to movement in humans.

Mechanoreceptor contribution to efferent autonomic outflow is incompletely understood. To determine the effects of mechanorceptor stimulation on autonomic reflexes, we compared autonomic responses in 34 subjects using a cross-over, counterbalanced design, in which hemodynamic, electromyographic, metabolic, and autonomic data were gathered during rest, passive, and active movement protocols. Because metaboreceptors and ventilatory responses influence autonomic outflow we verified and controlled for these influences during all protocols through comparisons of breath-by-breath gas exchange measurements. Verification of active and passive movements was made via electromyographic recordings of the moving legs. Spectral analysis of R-R variability was used to assess autonomic activity, and low to high frequency ratios were considered representative of sympathovagal balance. A repeated measures analysis of variance revealed significant modulating effects of mechanoreceptor stimulation on sympathovagal balance during passive movement upon efferent autonomic outflow (p<0.01) independent of central command, chemoreceptor, and metaboreceptor stimulation. Furthermore, breathing frequency and volume were identical for both movement protocols. Therefore, findings in this investigation suggest that modulating influences are being exerted by mechanoreceptor stimulation on autonomic outflow to the heart.

The Acute Effects of Acupuncture Upon Autonomic Balance in Healthy Subjects

Restoration of the sympathovagal (S/V) balance, involving a lowering of sympathetic and/or an augmentation of vagal modulation or a combination of both is associated with improvements in cardiovascular morbidity and mortality. To determine whether acupuncture exerts a favorable influence upon resting blood pressure and sympathovagal balance, a single-blind cross-over investigation was used to study the acute effects of acupuncture on S/V balance in normal healthy subjects. The ANOVA revealed a significant lowering of the sympathovagal balance (LF:HF) during rest for the acupuncture treatment from pre (4 +/- 2 nu) to post (2.2 +/- 1.8 nu)(p < 0.05). No such change was seen during sham treatment. The ANOVA revealed significant differences in systolic blood pressures during rest (114 +/- 4 vs. 108 +/- 3 mmHg) for the acupuncture treatment (p < 0.05). No significance was found during the sham treatment. The ANOVA failed to reveal any significant improvements in sympathovagal balance during the sustained isometric contraction. The clinical significance of these findings appears to suggest that acupuncture treatment might be beneficial in lowering blood pressure at rest. Furthermore, the lowering of the blood pressure might be in part due to a lowering of the sympathovagal balance. These findings are of importance since acupuncture treatments are non-pharmacological and have no known detrimental side-effects. This investigation employed healthy volunteers, yet acupuncture has been found to have more potent effects in animal models of hypertension and or in the presence of an autonomic imbalance.

Exercise training favourably affects autonomic and blood pressure responses during mental and physical stressors in African-American men.

Aerobic exercise is a powerful mechanism by which cardiovascular and autonomic parameters may be improved. We sought to quantify the extent of benefit that could be achieved by a short-term monitored exercise regimen on several autonomic parameters during recognized mental and physical stressors in young normotensive African-American men matched for a family history of hypertension, a group at high risk for the development of hypertension. Autonomic modulations were derived using spectral decomposition of the electrocardiogram and beat-to-beat blood pressures (BPs). Arterial compliance was obtained using contour analysis of the radial artery pulse wave. The analysis of variance revealed that compared with a matched sedentary control group, aerobic capacity of the trained group significantly increased by 16%. Autonomic modulations, arterial compliance and BP responses significantly improved during some of the stressors, whereas no such improvements were seen in the control group. Attenuated responses, mediated through a favourable shift in sympathovagal balance and enhanced arterial compliance, provide mechanistic evidence of how certain variables may be improved due to aerobic conditioning in a population at high risk for the development of hypertension.

Acetylsalicylic acid and autonomic modulation.

Loss of autonomic balance characterized by increased sympathetic activity and decreased vagal activity has been implicated as a major cardiovascular risk factor. Aspirins cardioprotective abilities involve a multitude of physiologic processes. However, the effects of aspirin on cardiac autonomic activity are unknown. In a double-blind crossover study, 22 subjects randomly received either aspirin or placebo in the amounts of 325 mg with each meal (three times per day) over a 2.5-day period. The total amount of aspirin ingested was 2,275 mg, which resulted in plasma levels of 3.3 mg/dl. At the conclusion of each treatment, subjects were evaluated for autonomic physiology activity using standard autonomic tests. Power spectral analyses of the electrocardiograms were used to delineate autonomic function. A 2×4 repeated measures analysis of variance revealed significant and favorable changes in autonomic activity after the use of aspirin. Specifically, at rest high-frequency (HF) power was significantly higher (mean, 1,090±1,463.5 msec2) compared with the placebo (mean, 692±742 msec2) (p<0.05). Low-frequency (LF) power was significantly reduced (mean, 963±745 msec2) after aspirin compared with placebo (mean, 1,100±906 msec2). After the aspirin treatment, a significantly lower LF-to-HF power ratio (mean, 1.7±2 msec2) was noted at rest when compared with the placebo (mean, 2.5±2.7 msec2) (p<0.05). Similar significant trends were seen during the sustained isometric contraction after aspirin therapy for HF power (mean 210±2.15 msec2) compared with placebo (mean, 213±184 msec2) (p<0.05). Accordingly, the LF-to-HF power ratio was lower as well when compared to placebo treatment (mean, 2.3±3.5 msec2) (mean, 5.3±8.4 msec2) (p<0.05). No differences were found in breathing rates for hemodynamic variables between any of the protocols. The significant reduction of LF-to-HF ratio, a marker of sympathovagal balance, for both protocols appeared to be largely due to a withdrawal of LF modulation and concomitant but lesser increase in HF modulation. Favorable alterations in autonomic outflow through prostaglandin inhibition may be one of the mechanisms by which low therapeutic amounts of aspirin provide prophylactic cardioprotection.

Value of Angiotensin receptor blocker therapy in diabetes.

There are more clinical trials investigating angiotensin receptor blockers (ARBs) in diabetes than any other drug class, ranging from early “prevention” trials to the treatment of individuals with advanced organ damage. In its earliest manifestations, visceral adiposity predisposes to hypertension and hyperglycemia (metabolic syndrome). In these individuals, ARB therapy delays the progression to chronic hypertension and may also delay the progression to overt diabetes. Based on the increased cardiovascular disease risk of the metabolic syndrome, which is similar to stage 1 hypertension, both lifestyle modification and ARB therapy are justifiable. ARB therapy has also been found to delay the onset of microalbuminuria and retinopathy. In established diabetic nephropathy, ARB therapy is recommended as a standard alternative to angiotensin‐converting enzyme inhibition to reduce macroalbuminuria and delay the progression to end‐stage disease. Finally, large trials in ischemic heart disease, heart failure, and stroke have demonstrated clear benefits of ARB therapy. Because ARBs have side effect rates equal to placebo and far lower than any other antihypertensive drug class, the benefit/risk ratio is highly favorable across the entire spectrum of diabetic disease. Thus, ARB therapy is a highly attractive alternative for individuals at any stage of diabetes and with any pattern of complications. J Clin Hypertens (Greenwich). 2011;13:290–295.

Combined aliskiren-amlodipine treatment for hypertension in African Americans: clinical science and management issues.

While it may seem at first that antihypertensive drug combinations run counter to the desire to ‘personalize’ the management of hypertension, the best combinations have predictable efficacy in different individuals and subpopulations. Race is probably not a valid surrogate for clinically meaningful genetic variation or guide to therapy. Most guidelines suggest similar blood pressure goals for different races but drug treatment recommendations have diverged. In the United States, race is not considered to be a major factor in drug choice, but in England and other countries, initial therapy with renin–angiotensin system blocking drugs is not recommended in Blacks. In this review we: (1) examine new trends in race-based research; (2) emphasize the weaknesses of race-based treatment recommendations; and (3) explore the effects of a new combination, renin inhibition (aliskiren) and amlodipine, in African Americans.

Combination therapy with aliskiren and amlodipine in hypertension: treatment rationale and clinical results.

Optimal antihypertensive therapy requires a multimodal approach based on lifestyle modification and, for most individuals, combination drug therapy. Recommendations from experts suggest that a combination of an agent that blocks the renin–angiotensin system (RAS), together with a vasodilator (generally a calcium-channel blocker or a thiazide-type diuretic), is most likely to control blood pressure and provide the widest overall cardiovascular protection. Understanding the opportunities afforded by the combination of RAS blockade with a calcium-channel blocker requires a discussion of basic and clinical science data. One new concept is that of ‘global’ or total RAS blockade. The impact of the RAS can be diminished or blocked by several different classes of drugs (central sympatholytics, β-blockers, renin inhibitors, ACE inhibitors or ARBs); what is most important is how effectively the overall impact of angiotensin II is blunted. A second new concept is that the complementary actions of RAS blockers and calcium-channel blockers are best explained on the basis of diminished intracellular calcium availability in excitable tissue (sympathetic neurons and vascular smooth muscle cells) via parallel actions that reduce angiotensin II type-1 receptor stimulation and L-channel-mediated calcium flux. Aliskiren is the first of the direct renin inhibitors, the newest subclass of RAS blockers. In both short- and long-term studies, aliskiren has been shown to be similar in efficacy and tolerability compared with other RAS blockers, with the added benefit that its effects persist longer. Outcome studies with aliskiren are currently underway.

A Cardiologist’s View of Hypoglycemia

Recent studies have failed to show an improvement in cardiovascular mortality with intensive glycemic control and aggressive glycated hemoglobin (A1c) targets less than 7.0%. Excessive hypoglycemic episodes with intensive glucose-lowering therapy are thought to be a major factor in the failure to show cardiovascular benefit in these trials. In this article, we review the physiology of glucose metabolism, the cardiovascular pathophysiology of hypoglycemia, and the trials with an intensive glucose-lowering strategy that have studied microvascular and macrovascular complications. We also review the current non-insulin drugs available for the treatment of diabetes and their potential hypoglycemic and cardiovascular impacts.