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.

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.

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, ß-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.

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.

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 (A(1c)) 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.

Effect of glitazones on the progression of coronary artery disease in type 2 diabetes patients.

The effect of thiazolidinediones (TZDs) on the progression of atherosclerosis in diabetes patients remains unclear. There has been heightened interest in recent years in this class of diabetes medications due to the non-glycemic lowering effects, such as altering lipids, inflammation and hematologic profiles. There have been several exciting studies over the past few years focused on the mechanism of action of the TZDs with respect to alteration in the cardio-metabolic profile in diabetes patients. New tools such as intravascular ultrasound have been used to follow plaques characteristics over time on a much more sensitive scale than has ever been possible in the past by coronary angiograms. These advances have enabled researchers to follow closely the macrovascular effects of different anti-atherosclerotic medications such as statins and TZDs. This article reviews the pathophysiology of atherosclerosis in diabetes, the role that TZDs play in this process and the imaging trials looking at the progression or regression of atherosclerosis in patients treated with TZDs.

Impaired fasting glucose as a treatment target in diabetes management.

Impaired fasting glucose (IFG) contributes to microvascular and macrovascular complications and increased cardiovascular disease risk. Although type 2 diabetes is largely considered to occur as a result of IFG, understanding of physiologic and associated management targets is uniformly lacking among health care professionals. Once definitions are standardized, diagnostic criteria and screening tools may help to identify individuals at risk sooner, thereby minimizing the rapid deterioration that often results. To counter the rising pandemic of obesity and diabetes, it is important to understand the vascular risk of IFG and impaired glucose tolerance in patients at risk.

PPARgamma agonists and coronary atherosclerosis.

The prevalence of type 2 diabetes mellitus (T2DM) is growing at an alarming rate and reaching epidemic proportions, and cardiovascular disease continues to be one of the leading causes of death in the United States. The key relationship between these two diseases (knowing that T2DM is a strong risk factor for cardiovascular disease) is insulin resistance and the detrimental effect it has on macrovasculature. Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gammaagonists that are beneficial in the treatment of T2DM and have the added benefit of modifying lipid profiles. This review discusses the basic science linking insulin resistance to atherosclerosis and describes the major TZD trials in the recent literature. It also addresses the clinical implications of these studies and media scrutiny surrounding the recent controversial report that TZDs may be linked to an increased risk of myocardial infarction.

Exercise training improves cardiovascular and autonomic profiles in HIV.

OBJECTIVES: Human immunodeficiency virus (HIV) is associated with cardiovascular (CV) and autonomic dysfunction, however the effects of fitness on vascular and autonomic mechanisms in HIV disease are unknown. METHODS: We studied forty-eight subjects (40.4 +/- 4.2 years) in a cross-sectional design matched for age, gender, BMI, and fitness. Participants were assigned to 1 in 4 groups: 1) Healthy Unfit (HU), 2) Healthy Fit (HF), 3) HIV Positive Unfit (HPU), and 4) HIV Positive Fit (HPF). Fitness was assessed via open-circuit spirometry; arterial compliance and autonomic modulations were measured via applanation tonometry and power spectral analysis, respectively, and baroreflex sensitivity was obtained using the alpha index. RESULTS: Arterial compliance was augmented in HPF vs. HPU [7.4 +/- 1.9 mmHg x second vs. 4.4 +/- 1.7 mmHg x second (P = 0.006)]. Parasympathetic modulation was higher in HPF vs. HPU [2244.5 +/- 2997.6 msecond(2) vs. 489.1 +/- 552.9 msecond(2) (P < 0.05)]. Sympathetic modulation was lower in HPF vs. HU [4.7 +/- 5.0 mmHg(2) vs. 12.9 +/- 9.7 mmHg(2) (P < 0.05)]. Baroreflex sensitivity was higher in HPF vs. HPU [17.3 +/- 10.2 msecond/mmHg vs. 7.4 +/- 3.8 msecond/mmHg (P = 0.003)], and HPF vs. HU [17.3 +/- 10.2 msecond/mmHg vs. 6.2 +/- 3.0 msecond/mmHg (P = 0.004)]. CONCLUSIONS: Augmentations in arterial compliance and baroreflex sensitivity associated with fitness portent an improved CV and autonomic profile for HIV-positive individuals. Physical activity may be an adjuvant method to enhance the overall vascular health in HIV-compromised individuals.

Vasomotor symptoms in menopause: where we've been and where we're going.

The decline in gonadal hormones during menopause gives rise to a wide range of physiological and psychological changes with the potential to significantly impact a woman's health and quality of life. Most notable among these are menopausal vasomotor symptoms, hot flushes and night sweats, along with mood and sleep disturbances. Given the biological and social significance of menopause, it is remarkable that the language used to describe this event and its associated symptoms is inconsistent. This review traces the history of Western medical writing about menopause-associated vasomotor symptoms and considers how terminology has contributed to the current confusion regarding symptoms and symptom reporting. Although hormone therapy is the only treatment for menopausal symptoms currently approved by the U.S. Food and Drug Administration, other forms of therapy are under evaluation. Agreement about the definition of menopause and its associated symptoms is critically important for the design and evaluation of new therapies and for the optimal treatment of women during this important phase of their lives.

Low arterial compliance in young African-American males.

Hypertension remains a common public health challenge because of its prevalence and increase in co-morbid cardiovascular diseases. Black males have disproportionate pathophysiological consequences of hypertension compared with any other group in the United States. Alterations in arterial wall compliance and autonomic function often precede the onset of disease. Accordingly, our purpose was to investigate whether differences exist in arterial compliance and autonomic function between young, healthy African-American males without evidence of hypertension and age- and gender-matched non-African-American males. All procedures were carried out noninvasively following rest. Arterial compliance was calculated as the integrated area starting at the well-defined nadir of the incisura of the dicrotic notch to the end of diastole of the radial artery pulse wave. Power spectral analysis of heart rate and blood pressure variability provided distributions representative of parasympathetic and sympathetic modulations and sympathovagal balance. Baroreflex sensitivity (BRS) was calculated using the sequence method. Thirty-two African-American and twenty-nine non-African-American males were comparable in anthropometrics and negative family history of hypertension. t-Tests revealed lower arterial compliance (5.8 +/- 2.4 vs. 8.6 +/- 4.0 mmHg. s; P = 0.0017), parasympathetic modulation (8.9 +/- 1.1 vs. 9.7 +/- 1.1 ln ms2; P = 0.0063), and BRS (13.7 +/- 7.3 vs. 21.1 +/- 8.5 ms/mmHg; P = 0.0007) and higher sympathovagal balance (2.9 +/- 3.2 vs. 1.5 +/- 1.1; P = 0.03) in the African-American group. In summary, differences exist in arterial compliance and autonomic balance in African-American males. These alterations may be antecedent markers of disease and valuable in the detection of degenerative cardiovascular processes in individuals at risk.

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.