W. A. Littler

Assessment of left-ventricular mass and its response to antihypertensive treatment.

50 patients with mild to moderate essential hypertension underwent M-mode echocardiography and continuous intra-arterial ambulatory monitoring of blood pressure. Indices of left-ventricular (LV) mass were derived from echocardiographic data by standard formulae. 43 of the patients were followed up for 12+/-7 months with repeat M-mode echocardiography, and casual blood-pressure measurements. 25 of these patients received antihypertensive therapy and 18 were untreated. Mean 24 h systolic blood pressure was significantly correlated with echocardiographic LV mass; mean 24 h diastolic blood pressure was also correlated, but the relation was weaker. In the treated group there was a significantly greater fall in blood pressure and LV mass index than in the untreated group, and there was a significant correlation between the fall in systolic blood pressure and the fall in LV mass index in the treated group. Systolic blood pressure appears to be an important factor in the pathogenesis of LV hypertrophy, and in hypertensive patients changes in LV mass assessed by echocardiography correlate with changes in blood pressure.

USEFULNESS OF OPHTHALMOSCOPY IN MILD TO MODERATE HYPERTENSION

A panel of two physicians and two ophthalmologists examined 25 patients with untreated essential hypertension by direct ophthalmoscopy and assessment of fundal photographs; daytime ambulatory sphygmomanometric blood pressure monitoring, estimation of left ventricular mass by electrocardiography and two-dimensional echocardiography, and measurement of urinary microalbumin excretion were also carried out. No relation was found between blood pressure determined by clinic or ambulatory sphygmomanometry and retinopathy. The retinal features sought on fundal photographs were the percentages of arteriovenous crossings with venule nipping, venule deviation, or attenuation of venular light reflex. The ratio of arteriolar to venular diameter was measured. Only focal narrowing of arterioles was associated with higher blood pressure. There was no independent relation between retinal features and age, measures of left ventricular mass, or urinary microalbumin excretion. Assessment of arteriovenous crossing abnormalities by direct ophthalmoscopy was subject to wide variability among the panel members. Direct ophthalmoscopy was not clinically useful in the assessment of mild to moderate hypertension, whereas urinary microalbumin excretion correlated strongly with clinic blood pressure.

Factors determining direct arterial pressure and its variability in hypertensive man.

SUMMARY Infra-arterial pressure was recorded continuously in 26 patients with uncomplicated essential hypertension under standardized conditions. Recordings were analyzed beat by beat to obtain mean pressures and variability, expressed as tbe standard deflation of the frequency histogram. The major factors influencing variability were tbe level of pressure and tbe Intensity of physical activity; systolic variability increased with progressive impairment of sino-aortic baroreflexes. Diastollc pressure increased with the level of sympathetic activity as reflected by plasma noreplnephrine levels. After allowance for the decrease of plasma renin activity (PRA) with age, direct relationships were observed between PRA (log values) and the level of pressure and systolic variability; plasma angiotensin II values did not correlate. Systolic variability increased with the systolic response to cold but was unrelated to the response to dynamic or isometric exercise. Variability also tended to increase with obesity and was unrelated to age, sex, or race.

Direct arterial pressure, heart rate, and electrocardiogram during cigarette smoking in unrestricted patients

Direct arterial pressure, heart rate, and ECG have been recorded over a 24-hour period in nine individuals who were completely unrestricted throughout the study. Forty-nine separate cigarette smoking episodes were clearly indicated and analyzed. The results of our study confirm a significant increase in arterial pressure five minutes after smoking a cigarette. The systolic rise in pressure (mean 10.7 mm. Hg, P less than 0.001) was approximately twice that of the diastolic rise (5.3 mm. Hg, P less than 0.001) and was present under different conditions of everyday life with notable exception of lying in bed before sleep, We found no quantitative difference between normotensive and hypertensive subjects. There was no certain change in heart rate (mean increase +0.8 beats per minute, t equals 0.59, NS) in the group as a whole. Smoking also had a short-term action consisting of a brief fall in arterial pressure and heart rate occuring over eight to ten heart beats following immediately after the first inhalation of tobacco smoke, followed by a rebound rise in arterial pressure to a level greater than the presmoking level; this is probably a vagal effect. Cigarette smoking caused angina pectoris in one individual and the records showed ST-segment depression in the ECG before the subjective appreciation of pain.

Variation in cuff blood pressure in untreated outpatients with mild hypertension―Implications for initiating antihypertensive treatment

: Thirty-two patients with mildly elevated blood pressure (BP), but without target organ damage, attended a BP measuring clinic where duplicate BP measurements were made on 12 visits. During visits 1-3, BP showed a systematic decrease which varied from patient to patient. During visits 4-12, no further systematic changes in BP were observed. During the latter period, between-visit variation in BP was substantial, the standard deviation of the difference in BP from one visit to another being 10.4 mmHg for systolic, 6.8 mmHg for diastolic (phase IV) and 7.0 mmHg for diastolic (phase V). These values were used to determine the chance that the BP estimated after a number of visits differed from the average stable BP. After visit 4, the chance of a difference of 5 mmHg or more was 0.50 systolic blood pressure (SBP) and 0.32 diastolic blood pressure (DBP; phase V). Increasing the number of visits to six or more reduced the chance of error. Before initiating lifelong treatment in mild hypertensives free of target organ damage, BP should be recorded in duplicate on a minimum of six visits.

Changes in plasma norepinephrine, blood pressure and heart rate during physical activity in hypertensive man.

SUMMARY We have investigated the changes in plasma norepinephrine and blood pressure and heart rate during a range of physical activities in eight hypertensive subjects in order to determine whether changes in plasma norepinephrine reflect changes in sympathetic activity. Blood pressure was recorded over 24 hours from an intra-arterial cannula. Plasma norepinephrine, measured by a sensitive radioenzymatic method, increased progressively with increasing levels of physical activity. In each subject a statistically significant linear relationship was observed between the logarithm of plasma norepinephrine and systolic blood pressure. Analysis of variance showed that 66% of the variance of plasma norepinephrine was associated with changes in blood pressure and heart rate. These observations support the hypothesis that plasma norepinephrine reflects short-term changes in sympathetic activity. Use of the quantitative relationship described, in conjunction with measurements of norepinephrine metabolism, may help to determine the significance of increased levels of plasma norepinephrine observed in some hypertensive patients.

Modulation of Cardiac Autonomic Control in Humans by Angiotensin II

Angiotensin II (Ang II) exerts an inhibitory action on vagal activity in animals and may also facilitate sympathetic activity. The object of this study was to compare autonomic activity resulting from equivalent steady-state baroreflex activation during intravenous Ang II infusion with that resulting from a control infusion of phenylephrine. Eight healthy subjects aged 22 to 34 years were studied in a single-blind, randomized, prospective crossover study. Autonomic activity was determined by computer analysis of RR interval variability in the time and frequency domains. Despite equal experimental hypertension with Ang II and phenylephrine infusion, at peak infusion rates the mean RR interval was significantly shorter with Ang II (983 +/- 179 milliseconds; mean +/- SD) than with phenylephrine (1265 +/- 187 milliseconds, P < .01). The variability of RR intervals was not significantly different, but the variability (median interquartile difference) of RR interval successive differences was significantly lower with Ang II (66 milliseconds) than with phenylephrine (104 milliseconds, P < .02). Power spectral analysis revealed the power of the 0.25-Hz component in normalized units to be significantly smaller during Ang II infusion (20.5 +/- 12.7 U) than during phenylephrine (38.2 +/- 14.7 U, P < .05), whereas the power of the 0.1-Hz component was significantly greater during Ang II infusion (67.8 +/- 17.1 U) than phenylephrine (38.8 +/- 20.3 U, P < .05). Measures of vagal modulation of heart rate were significantly attenuated, and sympathetic modulation appeared to be increased during Ang II infusion compared with control phenylephrine infusions. These observations may underlie reports of increased vagal activity during angiotensin-converting enzyme inhibitor therapy.

Cardiovascular response in black and white hypertensives.

Sixteen untreated black patients with mild- to- hypertension and no evidence of target organ damage were matched for age, sex, casual blood pressure (BP), and socioeconomic status with 16 white hypertensives. All patients were studied under standardized conditions in the hospital where they underwent continuous intraarterial ambulatory monitoring of BP and assessment of BP control mechanisms. BP characteristics over prolonged periods of recording were similar for both groups, as were sinoaortic baroreflex activity and pressor response to isometric and dynamic exercise and to cold. Fasting cholesterol and triglyceride levels in both groups were similar. Resting plasma renin activity (PRA) was significantly lower in blacks, but no difference was observed in resting plasma norepinephrine levels. Urinary excretion of Na+ and K+ was also similar in both groups. Thus, results showed that casual BPs matched for black and whites, and recorded over a prolonged period, were similar in pattern, variability, and response to pressor stimuli. It appears that, if BP contributes to the different patterns of morbidity in blacks and whites, it is more likely to be the actual level of BP rather than differences in BP characteristics. (Hypertension 4: 817–820, 1982)

Regression of Left Ventricular Hypertrophy in Hypertension: Comparative Effects of Three Different Drugs

We examined the effect of three antihypertensive agents with differing modes of action on blood pressure, heart rate, plasma catecholamines, plasma renin activity, and echocardiographic left ventricular mass. Twenty-six patients were studied; nine were treated with nifedipine, a calcium antagonist, nine were treated with timolol, a nonselective beta-blocker, and eight were treated with indapamide, a diuretic with some probable calcium antagonist properties. All drugs reduced blood pressure satisfactorily; the reduction of systolic blood pressure was not significantly different among the three drugs, but timolol reduced diastolic blood pressure by a greater amount than did either indapamide or nifedipine. Left ventricular (LV) mass was reduced equally by all three drugs. However, there were markedly different effects on the other parameters measured. Heart rate was reduced to a greater extent by timolol than by the other two drugs. Plasma renin activity was reduced by timolol, unchanged by nifedipine, and increased by indapamide. There were no significant changes in either adrenaline or noradrenaline with any of the three drugs. We conclude that these data do not support the hypothesis that the sympathetic nervous system is primarily responsible for left ventricular hypertrophy, and suggest that reduction of left ventricular mass with antihypertensive agents is not the property of any one class of drug.

Effect of quinapril on blood pressure and heart rate in congestive heart failure

The effect of quinapril on blood pressure (BP), heart rate (HR) and their variabilities in 12 patients with severe congestive heart failure (New York Heart Association class III and IV) was assessed using ambulatory electrocardiographic and intraarterial monitoring. Mean +/- standard deviation daytime BP was 122/75 +/- 20/15 mm Hg at baseline and 113/70 +/- 13/16 mm Hg after 16 weeks of therapy with quinapril (p greater than 0.05 for systolic and diastolic BP); mean nighttime BP was 114/69 +/- 19/14 mm Hg at baseline and 107/69 +/- 15/14 mm Hg with quinapril (p greater than 0.05 for systolic and diastolic BP). Mean daytime HR was unchanged but nighttime HR was reduced from 77 +/- 11 to 71 +/- 10 beats/min, p = 0.02. HR variability (difference between the 75th and 25th percentiles of the frequency distribution of RR intervals) increased from 91 +/- 34 to 134 +/- 47 ms, p = 0.008. The variability of successive differences between RR intervals also increased significantly (75th to 25th percentile = 17 +/- 4 ms at baseline and 31 +/- 26 ms with quinapril, p = 0.02). Long-term quinapril caused clinically unimportant decreases in BP in patients with severe congestive heart failure. An increase in vagal activity caused by the reduction in circulating angiotensin II may account for the effect of converting enzyme inhibition on HR and its variability.