Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease.

AIMS: The aim of this study was to assess the prognostic importance of peripheral arterial disease (PAD) as evaluated by ankle blood pressure index (ABI), and the impact of ramipril on the prevention of major cardiovascular events in PAD patients included in the Heart Outcomes Prevention Evaluation (HOPE) study. METHODS AND RESULTS: Patients were randomized to treatment with ramipril or placebo and followed for 4.5 years. Ankle brachial blood pressure index was measured, mainly by digital palpation of the foot pulse, at baseline in 8986 patients. The ABI was subnormal (< or =0.9) in 3099 patients and normal in 5887 patients. A low ABI was a strong predictor of morbidity and mortality during the follow-up even in patients with no clinical symptoms of PAD (n=6769). This was so for the primary outcome of the study; ABI>0.9:13.1%, 0.6-0.9: 18.2% and <0.6: 18.0% (P<0.0001) and for mortality from all causes: in those with a normal ABI it was 8.5%, in those with ABI >0.6-0.9, 12.4% and 14.2% in those with an ABI lower than 0.6 (P<0.0001). Ramipril reduced the risk of clinical outcomes in those with a clinical history of PAD as well as in the patients with subclinical PAD. CONCLUSIONS: The ABI even if measured simply by palpation of the foot arteries is a strong predictor for future cardiovascular events and for all-cause mortality. Ramipril prevented major cardiovascular events in patients with clinical as well as subclinical PAD.

The relationship between cardiothoracic ratio and left ventricular ejection fraction in congestive heart failure. Digitalis Investigation Group.

BACKGROUND: Left ventricular ejection fraction (EF) is a valuable prognostic index in patients with congestive heart failure (CHF). Although EF can be readily measured, many clinicians use roentgenographic heart size as a clue to differentiate systolic from diastolic dysfunction, even in the absence of solid supportive data. OBJECTIVE: To test the hypothesis that the cardiothoracic ratio (CTR) measured from the chest roentgenogram can be used to estimate left ventricular EF in individuals with CHF. METHODS: To answer this question, the database of the Digitalis Investigation Group trial was used. The CTR, determined using the Danzer method, and quantitative EF, measured locally using angiographic, radionuclide, or 2-dimensional echocardiographic techniques, were compared in 7476 patients with clinical CHF (New York Heart Association functional classes I-IV) due to acquired left-sided cardiac disease of ischemic, hypertensive, idiopathic, and alcohol-related causes. RESULTS: Mean (+/-SD) CTR for the cohort was 0.53+/-.07. Mean (+/-SD) EF was 31.7%+/-12.2%. A weak, negative correlation between CTR and EF was observed (r=-0.176). Similar findings were obtained when the results were stratified by cause of CHF, presence of clinically defined right ventricular dysfunction, and method of EF measurement. Categorical analysis failed to yield a CTR cutoff point that facilitated useful segregation of individuals with an EF greater than 35% or 35% and below; greater than 40% or 40% and below; and greater than 45% or 45% and below in any patient group. CONCLUSIONS: Although a weak, negative correlation exists between CTR and EF, this relationship does not allow for accurate determination of systolic function in individual patients with CHF. Considering the morbidity and mortality associated with CHF, and the clinical implications of systolic function in this syndrome, direct measurement of EF is recommended.

Efficacy and safety of extended-release isosorbide mononitrate for stable effort angina pectoris.

The efficacy and safety of extended-release isosorbide mononitrate tablets were evaluated in patients with stable effort angina. In a double-blind study, 313 patients with stable effort-induced angina were randomized to receive placebo or extended-release isosorbide mononitrate: 30, 60, 120 or 240 mg once daily in the morning. Serial exercise testing was performed using the standard Bruce treadmill protocol on days 1, 7, 14, 28 and 42 immediately before morning drug administration, and 4 and 12 hours after administration. After initial dosing, all groups that received extended-release isosorbide mononitrate had significant (p < 0.01) increases in mean total exercise time of approximately 30 to 50 seconds in relation to placebo 4 and 12 hours after administration. On day 42, mean changes from baseline in total exercise time of patients who received 120 or 240 mg of extended-release isosorbide mononitrate exceeded placebo by approximately 50 to 60 seconds 4 hours after dosing (p < 0.01), and by 30 to 35 seconds 12 hours after dosing (p < or = 0.05). No significant difference was detected between responses to extended-release isosorbide mononitrate and placebo 24 hours after administration (i.e., immediately before the next dose). Thus, there was neither significant activity nor demonstrable rebound of effort-induced angina (zero-hour effect) at the end of the dosing interval. Transient headache was the most prevalent adverse experience. Extended-release isosorbide mononitrate (120 and 240 mg administered orally once daily) significantly prolonged exercise time to development of moderate effort-induced angina 4 and 12 hours after dosing during long-term therapy, without development of nitrate tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril stimulation of differential renins in renovascular hypertension.

Twenty-six patients being evaluated for renovascular hypertension were studied to assess the diagnostic value of enhancing the differential between renal venous renins (PRA) by a single 25 mg oral dose of converting enzyme inhibitor (CEI, captopril). Antihypertensive medications were not discontinued prior to the study, and renal venous effluent was sampled before and 30 minutes after CEI. Eight patients without stenosis who did not have surgery had post-CEI ratios of less than 3.0. The other 18 patients had operative intervention, with 14 subsequently having improved blood pressure control. Of these 14, seven patients with unilateral stenosis, four patients with bilateral stenosis, and one patient without overt stenosis but with other evidence of reduced renal blood flow had 30-minute PRA ratios of 3.0 or greater. Five of these 14 patients had prestimulation ratios of less than 1.5 and might not be considered operative candidates by conventional criteria. Four other patients unimproved by surgery had post-CEI ratios of less than 3.0 despite a baseline ratio of greater than 1.5 in two of four. Only two patients with post-CEI ratios of less than 3.0 were improved with surgery. We conclude that a 30-minute post-CEI renal venous ratio of 3.0 or greater enhances the probability that patients with renovascular disease, and hypertension will respond to surgical intervention with improved blood pressure control.

Long-term hemodynamic and metabolic effects of trimazosin in essential hypertension.

The long-term effects of trimazosin (TMZ) were studied in 26 male patients with mild essential hypertension. After a 2 wk single-blind placebo (P) period, 13 patients were randomly selected to receive TMZ and 13 P; they were followed for an additional 8 wk. TMZ was given in incremental doses of 25 to 50, 100 to 200, and finally 300 mg three times a day. The patients were seen at the clinic every 2 wk and their arterial pressures (AP) and heart rates (HRs) were measured in the supine (5 min) and upright (2 min) position. Blood chemistries, blood count, plasma volume (PV), plasma renin activity (PRA), plasma aldosterone (PA), and cardiac output (CO) were determined by ultrasound at the end of P and TMZ periods. TMZ decreased the AP and total peripheral resistance (TPR) at the higher dosages, but had no effect on PV, PRA, PA, CO, HR, or blood chemistry determinations. No effects were observed on any of the above parameters after P. We conclude that (1) TMZ is an effective and safe antihypertensive, (2) it lowers AP through reduction of TPR, and (3) its effect is dose related.

Hemodynamic correlates of autonomic reflexes in patients with labile and fixed hypertension.

the autonomic sympathetic reflexes to sustained handgrip, upright tilt and the Valsalva maneuver, were tested in 26 patients with labile and 26 with fixed essential hypertension. Sustained handgrip increased systolic (SAP), diastolic (DAP) and mean arterial (MAP) pressure, heart rate (HR), cardiac index (CI), tension time index (TTI) (p less than .01), and had no effect on total peripheral resistance index (TPRI) and left ventricular ejection rate index (LVERI) in both groups of patients. However, the response to upright tilt and the Valsalva maneuver was different in the two groups. Upright tilt in labile hypertensives increased DAP, MAP, HR, and TPRI (p less than .001); decreased CI, stroke index (SI) and LVERI (p less than .01) and had no effect on SAP. In fixed hypertensives, it decreased SAP, MAP, CI, SI and LVERI (p less than .001); increased HR (p less than .01) and had no effect on DAP, and TPRI. The diastolic pressure overshoot of the Valsalva maneuver was attenuated in fixed hypertensives compared to labile (p less then .001). Additionally, when the percent changes from control in DAP, MAP, HR and TPRI to sustained handgrip and upright tilt between the two groups were compared, only differences to upright tilt between the two groups were observed. The results of this investigation suggest that upright tilt and the Valsalva maneuver might serve as better predictors of autonomic reflexes in hypertensive patients than the grip test.

Systemic and renal hemodynamic effects of trimazosin: a new vasodilator.

Trimazosin was administered for 2 days in doses-ranging from 50 to 200 mg to 16 patients with essential hypertension. The patients were randomized on the third day and received either the active drug in a single dose of 300 mg or a placebo. Systemic hemodynamic studies in both the supine and 50 degrees upright tilt position, including the Valsalva maneuver and a 1 min sustained handgrip test at 30% maximal voluntary contraction, were performed during control and 0, 1, 2, and 3 hr after drug administration. Renal function studies including plasma renin activity (PRA) were performed during control period and 3 hr after drug administration. Trimazosin reduced arterial pressure and peripheral vascular and renal vascular resistances, increased heart rate, cardiac output, and renal blood flow, and had no effect on glomerular filtration rate or PRA. Placebo had no effect on any of the above-mentioned parameters. The increase in renal blood flow was independent of cardiac output. We conclude that trimazosin lowers arterial pressure through a direct arteriolar dilation and reduction in peripheral vascular resistance. Its direct renal effects would make it a useful agent in the treatment of hypertension associated with renal function impairment.

Racial differences in pressure, volume and renin interrelationships in essential hypertension.

The interrelationships of arterial pressure, plasma volume (PV), and plasma renin activity were studied in 152 consecutive male patients with uncomplicated essential hypertension. Of these, 22 (17 white and 5 black) subjects had normal plasma volumes and because of the small number were not included in the analysis of results. The remaining 130 (35 black and 95 white) patients were classified as having either expanded or contracted plasma volume. A higher percentage of black (43%) than white (21%) subjects were volume expanded (PV > 19 ml/cm) and a lower percentage of blacks (57%) than whites (79%) were volume contracted (PV < 17 ml/cm). There was not significant difference in mean arterial pressure and plasma renin activity between the volume expanded and contracted black patients. In contrast, the white patients with contracted plasma volume had significantly higher arterial pressures (p < 0.05) and plasma renin activity (p < 0.001) than those with expanded plasma volume. More blacks than whites had low plasma renin activity and did not manifest the inverse relationship of plasma renin activity to plasma volume as did the whites. These data confirm and extend previous observations that the relationship between plasma volume and plasma renin activity (PRA) in the male patient with essential hypertension seems to differ between the black and white race. Efforts to explain the low PRA in black patients might be best directed toward those patients with suppressed PRA and with contracted intravascular volume.