Effects of nifedipine-GITS on left ventricular mass and left ventricular filling.

Sixteen patients with initial diastolic blood pressure greater than or equal to 120 mm Hg were treated for 1 year with extended-release nifedipine [nifedipine-GITS (gastrointestinal therapeutic system)]. Serial changes in left ventricular mass index and associated alterations in left ventricular systolic function, left ventricular filling, plasma renin activity, atrial natriuretic peptide, and catecholamines were evaluated. Blood pressure was significantly reduced from 200 +/- 8/122 +/- 3 mm Hg (mean +/- SEM) to 144 +/- 5/89 +/- 2 mm Hg (p less than 0.0001) at 1 year. Eleven patients (69%) required only nifedipine-GITS for blood pressure control and 5 (31%) required the addition of chlorthalidone. After 6 months, the left ventricular mass index was significantly reduced by 19% from 121 +/- 8 to 96 +/- 7 g/m2 and this reduction was sustained at 1 year. Septal and posterior wall thicknesses were reduced from 13.4 +/- 0.1 to 11.2 +/- 0.04 mm and from 12.8 +/- 0.1 to 10.0 +/- 0.03 mm (p less than 0.001), respectively. Prevalence of left ventricular hypertrophy decreased from 63 to 25%. Left ventricular fractional shortening increased from 34 to 42% (p less than 0.05) and the relationship between fractional shortening and end-systolic stress did not change. Over the year of sustained blood pressure reduction, the peak velocity of early filling increased from 58 to 63 cm/s (p = 0.07), the peak velocity of late filling did not change, and the ratio of late to early peak velocity of left ventricular filling significantly decreased (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Normalization of left ventricular mass and associated changes in neurohormones and atrial natriuretic peptide after 1 year of sustained nifedipine therapy for severe hypertension.

Sixteen patients with severe hypertension were treated for 1 year with extended release nifedipine, during which time serial changes in left ventricular mass index and associated alterations in left ventricular systolic function, left ventricular filling, plasma renin activity, atrial natriuretic peptide and catecholamines were evaluated. Mean seated blood pressure (+/- SE) was significantly reduced from 200 +/- 8/122 +/- 3 to 144 +/- 5/89 +/- 2 mm Hg (p less than 0.0001) at 1 year. After 6 months, left ventricular mass index was significantly reduced by 19% from 121 +/- 8 to 96 +/- 7 g/m2 and this reduction was sustained at 1 year. Septal and posterior wall thickness were reduced from 13.4 +/- 0.1 to 11.2 +/- 0.04 mm and from 12.8 +/- 0.1 to 10.0 +/- 0.03 mm (p less than 0.001), respectively. The prevalence of left ventricular hypertrophy decreased from 63% to 25%. Left ventricular fractional shortening increased from 34 +/- 2% to 41 +/- 3% (p less than 0.05) and the relation between fractional shortening and end-systolic stress did not change. Over the year of sustained blood pressure reduction, the peak velocity of early filling increased from 57 +/- 3 to 63 +/- 4 cm/s (p = 0.07), peak velocity of late filling did not change and the ratio of late to early peak left ventricular filling velocity significantly decreased (p less than 0.05). Plasma atrial natriuretic peptide levels, markedly elevated at entry, decreased from 70 +/- 15 to 41 +/- 8 pg/ml at 1 year (p less than 0.05). Plasma renin activity and catecholamine levels were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolated T-wave abnormalities and evaluation of left ventricular wall motion after nifedipine for severe hypertension.

Rapid reduction of blood pressure by vasodilators in severe hypertensives has been associated with T-wave inversion. The significance of these changes in the absence of chest pain or other manifestations of ischemia is not known. To determine if these T-wave inversions are due to myocardial ischemia, we obtained electrocardiograms and left ventricular wall motion studies (2-D echocardiography) before and 1 h after rapid blood pressure reduction with nifedipine in 23 severe hypertensives. One hour after 10 mg nifedipine blood pressure was markedly reduced from 189 +/- 6/117 +/- 3 (mean +/- SE) to 151 +/- 5/91 +/- 3 mm Hg (P less than .001). New T-wave inversions developed in 6 of 23 (26%) subjects, but blinded evaluation of 2-D echocardiograms revealed no new wall motion abnormalities. Wall motion score, which at pretreatment was abnormal in 11 of 23 patients, improved significantly after nifedipine from 1.4 +/- 0.1 to 1.2 +/- 0.1 (P less than .05). Therefore, rapid and marked reduction of blood pressure with nifedipine is accompanied by a high incidence of asymptomatic T-wave inversions which are not accompanied by left ventricular wall motion abnormalities, suggesting that significant myocardial ischemia did not occur.

Effect of nifedipine GITS on left ventricular mass and diastolic function in severe hypertension.

Treatment of severe hypertension is beneficial, but reversibility of target-organ damage has not been characterized. Serial studies were performed in 15 patients with severe essential hypertension (age of 56 +/- 3 years, mean +/- SEM) treated for 1 year with 60 to 150 mg/day of continuous-release nifedipine; 3 patients required 50 mg of chlorthalidone/day to lower diastolic blood pressure (BP) to less than 95 mm Hg. Left ventricular (LV) structure and function was evaluated with two-dimensional-directed M-mode echocardiography, digitized from videotape and analyzed blindly. BP was markedly reduced from 194 +/- 8/115 +/- 4 to 146 +/- 4/88 +/- 14 mm Hg (p less than 0.0001) and maintained at this level for 1 year. Posterior wall and septal LV thickness, elevated at entry (12.9 +/- 0.1 and 13.4 +/- 0.1 mm), dropped steadily over 1 year into the normal range (10.0 +/- 0.03 and 11.2 +/- 0.1 mm, p less than 0.001). LV mass index, above 95% for normals at entry, decreased by 19% at 6 months (129 +/- 10 to 104 +/- 7 g/m2, p less than 0.01), and remained at this level at 1 year. LV fractional shortening rose steadily over 1 year from 34 to 42% (p less than 0.02). Atrial natriuretic peptide, which reflects LV filling pressures, was markedly elevated at entry, but was significantly reduced by 6 months (76 +/- 22 vs. 45 +/- 14 pg/ml, p less than 0.05). Sustained reduction of arterial BP with continuous-release nifedipine for 1 year normalizes LV mass, improves LV systolic function, and reduces circulating levels of atrial natriuretic peptide.

Differences in ambulatory blood pressure between men and women with mild hypertension.

Non-invasive ambulatory blood pressure monitoring was performed in a consecutive series of 87 subjects with recently detected mild uncomplicated hypertension. Obese subjects, diabetics and those with secondary hypertension were excluded. Ambulatory pressures were recorded on a day of usual activity. Average ambulatory systolic and diastolic pressures were significantly lower than referral pressures determined in clinics or screening sites and initial pressures taken by the monitors. Whereas men (57) and women (30) had similar referral and initial pressures, average ambulatory systolic pressure was significantly higher in men; diastolic pressure was not different. Men also had a significantly higher fraction of ambulatory systolic pressures greater than 140 mmHg compared to women. Fifty-six percent of the men and 80% of the women had average ambulatory systolic pressures less than 140 mmHg and diastolic pressures less than 90 mmHg; the difference between the sexes was significant (chi 2 = 6.99, P less than 0.01). Thus, in mild hypertension, women have lower average systolic pressure than men during ordinary daily activity. These results may account for lower long-term cardiovascular morbidity in hypertensive women compared with men.

Determinants of abnormal left ventricular filling in early hypertension.

Thirty-seven untreated subjects with borderline or mild hypertension were studied to establish the prevalence and clinical characteristics associated with abnormal left ventricular filling in this disorder. Subjects were referred to this study because of casual office blood pressure measurements of greater than or equal to 140/90 mm Hg; all were less than 50 years old, had no other cardiovascular or systemic disease and had not received antihypertensive medication for at least 1 year. To precisely determine blood pressure, measurements were made over 30 min with the patient in the supine position and during awake hours with ambulatory monitoring. Left ventricular mass was determined echocardiographically, and Doppler echocardiography was used to assess left ventricular filling. No subject had increased left ventricular mass, but 8 (22%) of the 37 had abnormal left ventricular filling. All eight subjects with abnormal left ventricular filling had an ambulatory systolic blood pressure greater than 130 mm Hg and a supine systolic blood pressure greater than 122 mm Hg. Abnormal filling was not related to left ventricular mass or heart rate. In multivariate analysis, the degree of abnormal filling could best be predicted from a combination of age and supine systolic blood pressure (r = 0.69; p less than 0.001). This study suggests that in untreated early essential hypertension, abnormal left ventricular filling is present in greater than 20% of subjects, precedes detectable left ventricular hypertrophy and is related to age and prevailing level of blood pressure.

Noninvasive ambulatory blood pressure monitoring in patients with recently detected systemic hypertension.

Noninvasive ambulatory blood pressure monitoring and Doppler echocardiography were used in a recent study evaluating persons aged 18 to 50 years who were initially found to have mild hypertension by casual blood pressure determination. Ambulatory blood pressure recordings were performed on a day of usual activity in 54 subjects; a subgroup of 24 patients had evaluation of left ventricular dimensions and diastolic filling patterns by Doppler echocardiography. Average ambulatory systolic pressures of 42% of subjects were greater than or equal to 130 mm Hg. Only 35% had average diastolic pressures greater than or equal to 85 mm Hg, and 57% had either systolic or diastolic pressures greater than or equal to 130/85 mm Hg. Correlation between casual and ambulatory pressures was not significant. No subject had left ventricular hypertrophy determined by echocardiography. Abnormal left ventricular diastolic filling was noted in 38% of those patients with average ambulatory pressures greater than or equal to 130/85 mm Hg, but in no patients with average pressures less than 130/85 mm Hg (p less than 0.05). These results suggest that ambulatory blood pressure monitoring may be a specific method for detecting those patients with mild hypertension who may have early and potentially reversible cardiac abnormalities.

Cardiac and hemodynamic adjustments to rapid and sustained blood pressure reduction.

The most effective strategies for achieving immediate and long-term control of blood pressure and reversal of left ventricular (LV) hypertrophy and dysfunction in severe hypertensives is not known. In this preliminary communication, we report our experience with long-term blood pressure control in severe hypertensives who were treated with up to 150 mg of nifedipine gastrointestinal therapeutic system (GITS)--a once daily nifedipine formulation. In 23 subjects with diastolic blood pressures greater than 120 mm Hg, treatment was begun with nifedipine capsules for immediate reduction of diastolic blood pressure to less than 110 mm Hg. Doppler echocardiography was used to measure LV mass, percent LV fractional shortening (%FS), and cardiac output (CO). To achieve a goal diastolic blood pressure of less than 95 mm Hg, the 22 subjects who responded to nifedipine capsules were titrated up to 150 mg of nifedipine GITS. To date, 12 subjects completed two months of goal blood pressure with nifedipine GITS. CO, heart rate (HR), and %FS were elevated following nifedipine capsules. During long-term therapy with nifedipine GITS, CO and HR returned to baseline, while %FS remained elevated. These preliminary data suggest that in patients with severe hypertension, effective long-term control of BP with a once-a-day dosage of nifedipine in the GITS formulation may be achieved without adverse hemodynamic effects.

Determinants of atrial natriuretic factor in the adult respiratory distress syndrome.

We measured plasma atrial natriuretic factor over the clinical course of 12 patients with the adult respiratory distress syndrome (ARDS). A total of 33 sequential measurements were correlated with 23 hemodynamic, pulmonary, and renal parameters. Atrial natriuretic factor was found to be eight times higher than age-matched healthy control subjects (p = 0.001). Although atrial natriuretic factor correlated well with pulmonary capillary wedge pressure (r = 0.592), there was no significant relationship between right atrial pressure and plasma atrial natriuretic factor (r = 0.258). Atrial natriuretic factor was best related to pulmonary artery systolic pressure (r = 0.751). We conclude that in ARDS, plasma atrial natriuretic factor is markedly elevated and arterial levels are best determined by left atrial pressure and pulmonary hemodynamics, and not by right sided cardiac pressures. The role of increased circulating atrial natriuretic factor in the pathophysiology of ARDS is to be clarified in future studies.

Effect of ambulatory blood pressure monitoring on the diagnosis and cost of treatment for mild hypertension.

Detection of mild hypertension by a small number of casual blood pressures may be inaccurate for the determination of average blood pressure. Nonetheless, casual pressures remain the basis for the diagnosis and treatment of hypertensive patients. We compared casual and noninvasive ambulatory blood pressure monitoring in a consecutive series of 60 subjects evaluated for possible mild hypertension on the basis of casual pressures. Ambulatory blood pressure monitoring was performed on days of usual activity. Correlations between casual systolic and average ambulatory systolic pressures or casual diastolic and average ambulatory diastolic pressures were not significant. Nearly half of the subjects had average ambulatory systolic pressures less than 130 mm Hg. Sixty percent had average ambulatory diastolic pressures less than 85 mm Hg. Nearly 40% had both systolic and diastolic pressures less than those limits. A preliminary analysis of the effects of these results on the short-term cost of antihypertensive treatment was made, assuming that treatment could be withheld from those with average ambulatory pressures less than 130/85 mm Hg. This approach suggests that ambulatory blood pressure monitoring need not increase overall cost, if the results of this evaluation are used in the decision to treat.