Primary care in the emergency department -- an untapped resource for public health research and innovation.

With rising patient volumes and increasingly complex cases, the specialty of emergency medicine faces a growing array of challenges. Efforts have been made to improve patient throughput, yet little attention has been directed to the increasing amount of primary care delivered in emergency departments (EDs) for chronic disease states such as hypertension and diabetes. Management of chronic medical conditions is traditionally seen as beyond the purview of the ED and emergency physicians tend to defer critical aspects of related patient care to other components of the healthcare continuum. As a result, vulnerable patients are often forced to navigate exceedingly complex and fragmented systems of care with little guidance, which often leads to inadequate treatment and exposure to increased risk for development of potentially avoidable complications. As evidenced by our experience with hypertension in an under resourced community, there is a crucial need for emergency physicians to espouse their role as providers of healthcare across the acuity spectrum and lead the way in defining regionally relevant solutions to better manage patients with chronic medical problems.

Efficacy and safety of initial combination therapy with amlodipine/valsartan compared with amlodipine monotherapy in black patients with stage 2 hypertension: the EX-STAND study.

The strategy of initiating hypertension treatment with combination versus single-drug therapy was formally tested in a prospective, double-blind, parallel-group trial in blacks with stage 2 hypertension (mean sitting systolic BP (MSSBP) >or=160 and <200 mm Hg). Participants were randomized equally to amlodipine/valsartan (A/V) (n=286) or amlodipine (A) monotherapy (n=286). After 2 weeks, there was forced titration of A/V 5/160 mg to A/V 10/160 mg and of A 5 to A 10 mg followed by 10 additional weeks of treatment. If SBP was >or=130 mm Hg at week 4, the protocol allowed optional titration of A/V to the 10/320 mg dose and, at week 8, hydrochlorothiazide 12.5 mg was optionally added to both A/V and A if SBP >or=130 mm Hg. Amlodipine/valsartan at week 8 lowered MSSBP last observation carried forward significantly>A (33.3 vs 26.6 mm Hg, P<0.0001). Lowering of MSSBP with A/V significantly exceeded that of A in several specified subgroups-the elderly (>or=65 years), isolated systolic hypertension, and those with body mass index (BMI) >or=30 kg/m(2). More patients treated with A/V than A achieved BP control (<140/90 mm Hg) both at weeks 8 (49.8 vs 30.2%; P<0.0001) and 12 (57.2 vs 35.9%; P<0.0001). Both treatment regimens were well tolerated. In conclusion, the strategy of initiating combination antihypertensive drug therapy in blacks with stage 2 hypertension with amlodipine /valsartan achieves greater and quicker reductions in BP as well as significantly higher BP control rates than starting treatment with amlodipine monotherapy.

Maximising antihypertensive effects of angiotensin II receptor blockers with thiazide diuretic combination therapy: focus on irbesartan/hydrochlorothiazide.

BACKGROUND: Evidence-based guidelines for the management of hypertension are now well established. Studies have shown that more than 60% of patients with hypertension will require two or more drugs to achieve current treatment targets. DISCUSSION: Combination therapy is recommended as first-line treatment by the JNC-7 guidelines for patients with a blood pressure > 20 mmHg above the systolic goal or 10 mmHg above the diastolic goal, while the International Society of Hypertension in Blacks recommends combination therapy when BP exceeds targets by > 15/10 mmHg. Current European Society of Hypertension-European Society of Cardiology guidelines also recommend the use of low-dose combination therapy in the first-line setting. Furthermore, JNC-7 recommends that a thiazide-type diuretic should be part of initial first-line combination therapy. Thiazide/diuretic combinations are available for a variety of classes of antihypertensive, including ACE inhibitors, angiotensin receptor blockers (ARBs), beta blockers and centrally acting agents. This article focuses on clinical data investigating the combination of an ARB, irbesartan, with the diuretic, hydrochlorothiazide. CONCLUSIONS: These data indicate that the ARB/HCTZ combination has greater potency and a similar side effect profile to ARB monotherapy and represents a highly effective approach for attaining goal BP levels using a therapeutic strategy that very effectively lowers BP, is well tolerated and minimises diuretic-induced metabolic effects.

The effect of doxazosin on sexual function in patients with benign prostatic hyperplasia, hypertension, or both.

The prevalence of both benign prostatic hyperplasia (BPH) and hypertension increases with advancing age. These conditions coexist in almost 25% of men aged 60 years and older. The use of transurethral prostatectomy, a common surgical therapy for BPH, alleviates symptoms but results in erectile dysfunction (ED) in up to 35% of patients. Pharmacological intervention for BPH, including androgen-suppressing agents, has resulted in an increased incidence of sexual adverse experiences compared with the incidence observed in patients receiving placebo. Patients with hypertension also frequently experience problems with sexual function; in addition, antihypertensive medications used to treat this disease may increase problems with sexual function. ED is an age-related phenomenon, with estimated prevalence rates of 39% among men 40 years old and 67% among those 70 years old. Doxazosin, an alpha1-adrenoceptor antagonist indicated for the treatment of patients with BPH and/or hypertension, is not associated with the occurrence of ED compared with other antihypertensive treatments.

Antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide in adult African Americans with mild to moderate hypertension.

BACKGROUND: African Americans with hypertension, particularly those with more severe blood pressure elevations, are generally less responsive to monotherapy from any antihypertensive class. These patients usually require treatment with drugs from > or = 2 antihypertensive classes to achieve adequate blood pressure control. OBJECTIVE: The purpose of this study was to assess the antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide (HCTZ) in African American adults with mild to moderate hypertension. METHODS: In this 12-week, multicenter, double-blind, randomized, parallel-group, placebo-controlled study, African American patients were randomized in a 3:3:1 ratio to I of 3 treatment groups: placebo, losartan monotherapy (50 to 150 mg), or losartan plus HCTZ (50/0 to 50/12.5 to 100/25 mg). Doses were titrated at weeks 4 and 8 if sitting diastolic blood pressure (SiDBP) was > or = 90 mm Hg. Safety was assessed by determining the incidence of clinical and laboratory Adverse events and evaluating mean changes in pulse, body weight, electrocardiographic parameters, and laboratory test results. RESULTS: A total of 440 patients were randomized-188 to placebo, 193 to losartan monotherapy, and 59 to losartan/HCTZ; 391 completed the study. At week 12, the response rate with losartan monotherapy was 45.8%, with a significant (P < or = 0.01) lowering in mean SiDBP by 6.6 mm Hg compared with placebo; the response rate with placebo was 27.2%, with a mean SiDBP reduction of 3.9 mm Hg. Sitting systolic blood pressure (SiSBP) was significantly lowered with losartan monotherapy, by 6.4 mm Hg, compared with placebo (reduction of 2.3 mm Hg). The response rate with losartan/ HCTZ was 62.7%, with reductions in SiSBP and SiDBP of 16.8 mm Hg and 10.8 mm Hg, respectively (P < or = 0.01 vs placebo and losartan monotherapy). The incidence of clinical adverse events was comparable in the 3 treatment groups. CONCLUSIONS: The results of this study suggest that in African American patients, losartan monotherapy was significantly more effective than placebo in lowering SiSBP and SiDBP. Moreover, the losartan/ HCTZ combination regimen resulted in significant and clinically meaningful additional reductions in SiSBP and SiDBP compared with losartan monotherapy or placebo. Losartan monotherapy and the losartan/HCTZ regimens were generally as well tolerated as placebo.

Coronary heart disease in African Americans.

African Americans have the highest overall mortality rate from coronary heart disease (CHD) of any ethnic group in the United States, particularly out-of-hospital deaths, and especially at younger ages. Although all of the reasons for the excess CHD mortality among African Americans have not been elucidated, it is clear that there is a high prevalence of certain coronary risk factors, delay in the recognition and treatment of high-risk individuals, and limited access to cardiovascular care. The clinical spectrum of acute and chronic CHD in African Americans is similar to that in whites. However, African Americans have a higher risk of sudden cardiac death and present more often with unstable angina and non-Q-wave myocardial infarction than whites. African Americans have less obstructive coronary artery disease on angiography, but may have a similar or greater total burden of coronary atherosclerosis. Ethnic differences in the clinical manifestations of CHD may be explained largely by the inherent heterogeneity of the coronary syndromes, and the disproportionately high prevalence and severity of hypertension and type 2 diabetes in African Americans. Identification of high-risk individuals for vigorous risk factor modification-especially control of hypertension, regression of left ventricular hypertrophy, control of diabetes, treatment of dyslipidemia, and smoking cessation--is key for successful risk reduction.

Salt sensitivity and hypertension in African Americans: implications for cardiovascular nurses.

Hypertension is a major public health problem in the U.S. Salt sensitivity is an important factor associated with hypertension and its complications, yet it has not been addressed in the nursing literature. Salt sensitivity is a directionally appropriate rise or fall in blood pressure when salt is added or removed, respectively. The change in blood pressure in salt-sensitive subjects occurs to a degree exceeding random blood pressure fluctuations. Salt sensitivity is present in 30% of normotensive and over 50% of hypertensive persons. It is more prevalent among African Americans, older persons, and individuals with renal insufficiency or diabetes. This paper provides nurses with an overview of salt sensitivity and its significance in hypertension. It presents conceptual and operational definitions of salt sensitivity, identifies factors contributing to its development, and describes implications for nursing practice.

Using angiotensin converting enzyme inhibitors in African-American hypertensives: a new approach to treating hypertension and preventing target-organ damage.

Angiotensin converting enzyme (ACE) inhibitors have been avoided as an initial therapeutic option in the treatment of hypertension in African-Americans. A major reason for this has been the widespread perception of clinicians that these agents have poor blood pressure (BP) lowering efficacy in this population. Remarkably uniform and pervasive interpretations of clinical trial data have formed the basis of this clinical perception and can be summarised as follows: (1) there has been a lesser BP lowering effect of ACE inhibitors in African-Americans compared to whites, particularly at low doses; and (2) short-acting ACE inhibitors like captopril prescribed at the midpoint of its maximal total daily dose lower BP less effectively than higher doses of calcium antagonists in African-Americans. A reinterpretation of published data from these same clinical trials suggests that: (1) the majority of African-Americans have meaningful BP responses to ACE inhibitors, albeit at a higher average dose than in whites; and (2) high levels of dietary sodium intake appear to explain a significant portion of the racial differences in BP response at the lower doses of ACE inhibitors. Thus, ACE inhibitors can effectively lower BP in African-Americans. These data suggest that the clinician should not avoid these agents in African-Americans because of a presumed lack of BP lowering efficacy. Rather, we should recognise the importance of adequate drug dosing and modest reductions in dietary sodium intake in augmenting the BP lowering effect of ACE inhibitors in hypertensive African-Americans.

The rapidity of drug dose escalation influences blood pressure response and adverse effects burden in patients with hypertension: the Quinapril Titration Interval Management Evaluation (ATIME) Study. ATIME Research Group.

BACKGROUND: Antihypertensive medication doses are typically increased within several weeks after initiation of therapy because of inadequate blood pressure (BP) control and/or adverse effects. METHODS: We conducted a parallel-group clinical trial with 2935 subjects (53% women, n=1547) aged 21 to 75 years, with Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI stages 1 to 2 hypertension, recruited from 365 physician practices in the southeastern United States. Participants were randomized either to a fast (every 2 weeks; n=1727) or slow (every 6 weeks; n=1208) drug titration. Therapy with quinapril, an angiotensin-converting enzyme inhibitor, was initiated at 20 mg once daily. The dose was doubled at the next 2 clinic visits until the BP was lower than 140/90 mm Hg or a dose of 80 mg was reached. RESULTS: Pretreatment BP averaged 152/95 mm Hg. Patients with stage 2 hypertension reported more symptoms than those with stage 1. The BP averaged 140/86, 137/84, and 134/83 mm Hg in the slow group compared with 141/88, 137/85, and 135/84 mm Hg in the fast group at the 3 respective clinic visits. The BP control rates to lower than 140/90 mm Hg at the 3 clinic visits were (slow, fast, respectively) 41.3%, 35.7% (P<.001); 54.3%, 51.5% (P=.16); and 68%, 62.3% (P=.02). In the fast group, 10.7% of participants experienced adverse events vs 10.8% in the slow group; however, 21.0% of adverse events in the fast group were "serious" vs only 12% in the slow group. CONCLUSION: Slower dose escalation of the angiotensin-converting enzyme inhibitor quinapril provides higher BP control rates and fewer serious adverse events than more rapid drug dose escalation.

Static and pulsatile blood pressure correlates of left ventricular structure and function in black and white young adults: the CARDIA study.

OBJECTIVE: To determine the unbiased relative strength of the association of static (systolic and diastolic) and pulsatile (pulse pressure) blood pressure components with left ventricular mass and function. BACKGROUND: Blood pressure is correlated with left ventricular mass; however, the unbiased relative strength of static and pulsatile blood pressure components with left ventricular mass and function is unknown in young adults. METHODS: Cross-sectional analyses of 3918 young adult participants at 4 community-based CARDIA clinical centers during 1990 and 1991. RESULTS: Left ventricular mass positively correlated (P <.01) with systolic, diastolic, and pulse pressure in all ethnicity-sex groups except for diastolic blood pressure in white men (P =.19). The association rank ordered as systolic blood pressure > pulse pressure > diastolic blood pressure except in white men, in whom pulse pressure and systolic blood pressure reversed positions in this hierarchy. Systolic blood pressure was the third and fourth strongest independent correlate of left ventricular mass in men and women, respectively. Body mass index, followed by height, was the strongest correlate of left ventricular mass in both sexes. Left ventricular wall thickness/chamber radius ratio positively correlated with diastolic and systolic blood pressure (women only) (P <.05) but not with pulse pressure. In all groups, stroke volume positively correlated (P <.05) with pulse pressure but was unrelated to static blood pressure measures, except for systolic blood pressure in black men. Left ventricular mass and the ventricular wall thickness/chamber radius ratio were greater in blacks compared with whites. CONCLUSIONS: Although systolic blood pressure was consistently the strongest unbiased blood pressure correlate of left ventricular mass, this relation varied by ethnicity and sex. Pulse pressure correlated with favorable left ventricular function and geometry, suggesting an opposite meaning to the ominous prognosis of wide pulse pressure in hypertensive, older adults.

Anthropometric and physiologic correlates of mitral valve prolapse in a biethnic cohort of young adults: the CARDIA study.

OBJECTIVE: To describe the epidemiology of echocardiographic mitral valve prolapse (MVP) and its anthropometric, physiologic, and psychobehavioral correlates with a cross-sectional analysis at 4 urban clinical centers. PATIENTS: A biethnic, community-based sample of 4136 young (aged 23 to 35 years) adult participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who had echocardiograms during their third examination between 1990 and 1991. MEASUREMENTS: Echocardiographic mitral valve prolapse, Doppler mitral regurgitation, blood pressure, anthropometry, and 4 psychobehavioral scales. RESULTS: Definite echocardiographic MVP prevalence was 0.6% overall and was similar across the 4 ethnicity/sex groups. Most participants (21 of 26, 80%) with definite echocardiographic MVP were unaware of their condition. Relative to persons with normal echocardiograms, those with echocardiographic MVP were taller (174.6 cm vs 171.0 cm, P <.01), leaner (26.7 mm vs 37.4 mm sum of triceps and subscapular skinfolds, P <.01), had lower body mass index (22.0 kg/m(2) vs 26.2 kg/m(2), P <.01), and more often has Doppler mitral regurgitation (34.8% vs 11. 8%, P <.01). Women with echocardiographic MVP had higher ethnicity-adjusted hostility scores (19.9 vs 16.1, P <.05) than women with no MVP. Among 111 (2.7%) of 4136 participants reporting prior physician diagnosis of MVP, only 5 (0.45%) of 111 had definite echocardiographic MVP. CONCLUSIONS: These data document a low prevalence of definite echocardiographic MVP and suggest a constellation of anthropometric, physiologic, and psychobehavioral characteristics in young adults with echocardiographic MVP. Most definite echocardiographic MVP diagnoses were discordant with self-reported MVP status, and false-positive diagnoses of echocardiographic MVP were made more often in women and whites.

Difficult-to-treat hypertensive populations: focus on African-Americans and people with type 2 diabetes.

The awareness, treatment, and control of hypertension has risen steadily over the past three decades, until the early 1990s. However, blood pressure control to < 140/90 mmHg is attained in fewer than 25% of all hypertensive patients and fewer than 50% of drug-treated hypertensive patients, except for white women. Two special populations, African-Americans and diabetics, share several important attributes. First, they both have a high prevalence of hypertension, including stage 3 hypertension (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension VI: > or =180/110 mmHg), relative to other subgroups. African-Americans have an approximate 8% prevalence of stage 3 hypertension, and elevated systolic blood pressure is highly prevalent among diabetic people, particularly older African-American women. Second, both groups have high levels of blood-pressure-related target-organ damage, which contributes to their inordinately high absolute risk for cardiovascular disease complications (i.e. stroke, congestive heart failure, renal failure) at a given level of blood pressure. Moreover, the reduced natriuretic capacity common to each group contributes to the attenuated efficacy of antihypertensive drug monotherapy, particularly for drug classes other than diuretics and calcium antagonists. These two special populations are also typically salt-sensitive, an intermediate blood pressure phenotype that raises blood pressure medication requirements. This phenomenon has been associated with an attenuation in the normal nocturnal fall in blood pressure. The high absolute risk for cardiovascular disease among diabetics led to the formulation of more aggressive treatment recommendations for antihypertensive drug therapy. In diabetics, blood pressure therapy is initiated at blood pressures > or = 130/85 mmHg, and treatment goals are at least to this level, unless proteinuria is > or = 1g/day (in which case the goals are < 125/75 mmHg). The more aggressive treatment targets for diabetics will not be reached with most currently available single antihypertensive agents in many African-Americans. While at best only 50-60% of hypertensive patients can be controlled with single drug therapy, that percentage falls dramatically in persons with stage 3 hypertension and renal insufficiency, thereby necessitating the use of combination drug therapy. Treatment alone is not enough; treatment to goal blood pressure is an essential first step towards optimal target-organ protection. While circulating levels of renin are suppressed, in general, in these special populations, each group manifests an inordinate burden of blood-pressure-related target-organ damage that has been linked to excessive levels of angiotensin II or a reduced bradykinin and nitric oxide tissue effect. The renin-angiotensin-aldo-sterone-kinin system is therefore an attractive therapeutic target that might conceivably provide target-organ protection over and above that attributable solely to lowering the blood pressure.

Urinary sodium and potassium profile of blacks and whites in relation to education in two different geographic urban areas. TOMHS Research Group. Treatment of Mild Hypertension Study.

The high Na/low K environment of modern society is related to the genesis of hypertension and stroke. There is prior evidence of racial, geographical, and social class differences in Na and K intake and blood pressure. Baseline data from the Treatment of Mild Hypertension Study (TOMHS) was used to assess urinary Na and K excretion profiles by race, clinic geographic area, and education. Participants were adult black and white hypertensive patients from the Birmingham, Alabama, and Chicago, Illinois, area. Level of education was categorized as: less than college graduate and college graduate or more. Two overnight urine samples were collected and analyzed for Na and K at entry from 154 blacks and 281 whites. The urinary Na:K ratio was significantly higher in both blacks (5.1 v 3.8, P < .001) and whites (4.1 v 3.4, P < .005) in Birmingham compared with Chicago. This was primarily due to the lower excretion of urinary K in blacks (12.8 v 16.9 mmol/8 h, P < .01) and whites (14.0 v 16.5 mmol/8 h, P < .01). The highest urinary Na:K ratio was observed in blacks in Birmingham with lower education level; urinary Na excretion was high in blacks with a lower education level in both cities. No such differences were seen in whites. Although TOMHS was not population-based, these findings suggest the possibility that potassium intake among persons with stage 1 hypertension is related to geographic area in both blacks and whites, and sodium intake is inversely related to education level in blacks.

Optimal blood pressure on antihypertensive medication.

The optimal blood pressure (BP) level for a patient on antihypertensive medication should maximize the patient's well-being and simultaneously lower the risk for pressure-related cardiovascular-renal complications. The clinical expression of pressure-related complications such as stroke, heart failure, renal insufficiency, peripheral arterial disease, and cognitive decline takes many years to decades to manifest. Accordingly, the attainment of the ultimate target BP is rarely necessary, or even desirable, over short time periods (eg, weeks) because the absolute clinical risk within these time periods is quite low. However, overmedication or aggressive BP lowering over the short term increases the likelihood of treatment-related side effects. Thus, attainment of goal BP should be accomplished gradually over many weeks to months in order to maximize BP lowering at a given dose of medication(s). Recent target BP goals promulgated by the Sixth Report from the Joint National Committee (JNC VI) are based on the premise that the intensity of treatment directly corresponds to the magnitude of pretreatment risk. Thus, hypertensive persons with diabetes, renal disease, or heart failure have goal BP levels lower than 130/85 mm Hg. All other hypertensive individuals should attain BP levels minimally to lower than 140/90 mm Hg. Finally, there is now appropriate recognition of the pivotal role of BP reduction in forestalling pressure-related cardiovascular complications, even among high-risk persons with diabetes mellitus and renal insufficiency.

Comparison of the efficacy of dihydropyridine calcium channel blockers in African American patients with hypertension. ISHIB Investigators Group. International Society on Hypertension in Blacks.

BACKGROUND: Hypertension is a prevalent disease among African Americans, and successful treatment rates are low. Since calcium channel blockers are well-tolerated and efficacious in African Americans, we undertook this study to compare the efficacy, safety, and tolerability of 3 commonly prescribed calcium channel blockers: amlodipine besylate (Norvasc), nifedipine coat core (CC) (Adalat CC), and nifedipine gastrointestinal therapeutic system (GITS) (Procardia XL). METHODS: One hundred ninety-two hypertensive patients across 10 study centers were randomly assigned to double-blind monotherapy with amlodipine besylate (5 mg/d), nifedipine CC (30 mg/d), or nifedipine GITS (30 mg/d) for 8 weeks. Patients not achieving therapeutic response after 4 weeks had their dose doubled for the next 4 weeks. The primary end point was a comparison of the average reduction (week 8 minus baseline) in 24-hour ambulatory diastolic blood pressure (DBP). Secondary end points included a comparison of average 24-hour ambulatory systolic blood pressure (SBP), office SBP or DBP reduction, responder rates, safety, and tolerability. RESULTS: One hundred sixty-three patients were evaluable for efficacy after 8 weeks. There was no significant difference in the average 24-hour ambulatory DBP (-8.5, -9.0, and -6.1 mm Hg, respectively) or SBP (-14.3, -15.7, and -11.8 mm Hg, respectively) reduction. Average office SBP and DBP were reduced to a comparable degree (19-22 mm Hg [P =.50] and 12-14 mm Hg [P =.51], respectively). Responder rates (DBP <90 or reduced by > or = 10 mm Hg) were similar (P = .38). Discontinuation rates and adverse event frequency were distributed similarly across the 3 treatment groups. CONCLUSION: The efficacy, safety, and tolerability of the 3 dihydropyridine calcium channel blockers are equivalent in African Americans with stages 1 and 2 hypertension.

Characterization of angiotensin-(1-7) in the urine of normal and essential hypertensive subjects.

A total of 31 healthy volunteers [39 +/- 7 (SD) years] and 18 untreated essential hypertensive subjects [43 +/- 9 years] collected urine for 24 h after a physical examination and laboratory tests. Radioimmunoassay measurements of angiotensin-(1-7) [Ang-(1-7)] in urine and plasma were done as described previously. Sitting systolic and diastolic blood pressures (+/- SD) averaged 118 +/- 11/74 +/- 7 mm Hg and 146 +/- 16/96 +/- 8 mm Hg in normal and essential hypertensive subjects, respectively (P < .001), whereas 24 h urinary volume was not different in normal and essential hypertensive subjects (P > .05). The concentration of Ang-(1-7) in the urine of normal subjects averaged 62.6 +/- 22.6 pmol/L corresponding to a urinary excretion rate of 98.9 +/- 44.7 pmol/24 h. Concurrent measurements of plasma Ang-(1-7) showed that the content of Ang-(1-7) in urine was 2.5-fold higher than that measured in the plasma. In contrast, untreated essential hypertensive subjects had lower concentrations and 24 h urinary excretion rates of Ang-(1-7) averaging 39.4 +/- 18.0 pmol/L and 60.2 +/- 14.6 pmol/24 h, respectively, (P < .001). Differences in the excretory rate of Ang-(1-7) between normal volunteers and essential hypertensive subjects were not modified by normalization of the data by urinary creatinine excretion rates. Urinary concentrations of Ang-(1-7) correlated inversely with systolic, diastolic and mean arterial pressures (r = -0.48, P < .001). Both urinary Ang-(1-7) [odds ratio of 0.92 (95% CI: 0.88-0.97)] and age were independent predictors of systolic blood pressure. These studies demonstrated the presence of Ang-(1-7) in urine and the existence of reduced levels of the heptapeptide in individuals with untreated essential hypertension. The relatively higher concentrations of Ang-(1-7) in urine compared to plasma agrees with data that showed that Ang-(1-7) may contribute to the regulation of blood pressure. The inverse association between Ang-(1-7) and arterial pressure provides a potential marker for the characterization of forms of essential hypertension associated with reduced production or activity of vasodilator hormones.

Renin-angiotensin-aldosterone-kinin system influences on diabetic vascular disease and cardiomyopathy.

Diabetes mellitus is associated with an inordinately high risk of virtually all manifestations of cardiovascular-renal disease including atherosclerotic coronary and peripheral vascular disease, congestive heart failure, stroke, nephropathy, and cardiomyopathy unassociated with coronary heart disease. Abnormalities in the renin-angiotensin-aldosterone-kinin (RAAK) cascade have been implicated in the pathogenesis and clinical expression of these cardiovascular-renal sequelae. Thus, pharmacological modulation of the RAAK system is an attractive therapeutic target in diabetes mellitus. Indeed, emerging data from human clinical studies appear to confirm this thesis.

Therapeutic strategies for hypertension treatment in patients with selected cardiovascular diseases.

Patients with hypertension and concomitant cardiovascular (CVD) conditions are at high risk for developing deleterious CVD-related clinical sequelae. The selection of therapeutic strategies for hypertension management in patients with cardiovascular diseases is an important first step in normalizing blood pressure (BP) levels (<140/90 mmHg). The ultimate goal of BP normalization for this high-risk group of hypertensive patients is target-organ protection. This review will discuss the management of hypertension in patients with selected CVD conditions (congestive heart failure, coronary artery disease, renal insufficiency/end-stage renal disease) and will incorporate both nondrug and drug therapies. Nondrug therapy, including weight reduction, physical activity, restriction of dietary sodium and alcohol intake are effective strategies for lowering BP. If these measures are not adequate, then the addition of drug therapy is needed in order to provide gradual BP normalization. Drug regimens may include a single antihypertensive agent with up-titration of the dose, or a combination of antihypertensive agents at a lower dose of each agent. The availability of different classes of antihypertensive agents enables therapeutics strategies to be implemented in the management of hypertension that provide maximum target-organ protection for each entity of CVD. Thus, aggressive hypertension management is crucial for delaying/preventing target organ damage and subsequent CVD clinical events.