Excessive Blood Pressure Reduction Research Articles

Aggressive blood pressure reduction in patients at high vascular risk: is it dangerous?

Introduction The aim of this review was to summarize the current state of evidence regarding the optimal blood pressure goals in patients with high vascular risk. In particular, this review critically addresses the issue of the “J-curve” paradox – a hypothesis indicating that low treatment-induced blood pressure values are characterized by an increase, rather than a decrease, in the incidence of cardiovascular events. Materials and methods We reviewed evidence from studies published in peer-reviewed journals indexed in Medline, EMBASE and CINAHL that compared different BP goals. Results Post-hoc analyses of randomized trials specifically conducted to test the hypothesis of the “J-shaped curve” yielded conflicting results. However, trials directly comparing different blood pressure goals and meta-analyses showed that in-treatment blood pressure values below the usual goal of less than 140/90 mmHg improve outcomes in patients at increased vascular risk. Discussion The fear that an excessive reduction in blood pressure may be dangerous is inconsistent with the available data and probably conditioned by the adverse impact of other risk factors that may be more frequent in patients with low values of achieved blood pressure. The association between blood pressure reduction and cardiovascular risk seems to be linear and not J-shaped.

Aggressive blood pressure reduction in patients at high vascular risk: is it dangerous?

The aim of this review was to summarize the current state of evidence regarding the optimal blood pressure goals in patients with high vascular risk. In particular, this review critically addresses the issue of the “J-curve” paradox – a hypothesis indicating that low treatment-induced blood pressure values are characterized by an increase, rather than a decrease, in the incidence of cardiovascular events. We reviewed evidence from studies published in peer-reviewed journals indexed in Medline, EMBASE and CINAHL that compared different BP goals. Post-hoc analyses of randomized trials specifically conducted to test the hypothesis of the “J-shaped curve” yielded conflicting results. However, trials directly comparing different blood pressure goals and meta-analyses showed that in-treatment blood pressure values below the usual goal of less than 140/90 mmHg improve outcomes in patients at increased vascular risk. The fear that an excessive reduction in blood pressure may be dangerous is inconsistent with the available data and probably conditioned by the adverse impact of other risk factors that may be more frequent in patients with low values of achieved blood pressure. The association between blood pressure reduction and cardiovascular risk seems to be linear and not J-shaped.

Clinical practices, complications, and mortality in neurological patients with acute severe hypertension: The Studying the Treatment of Acute hyperTension registry

To determine the demographic and clinical features, hospital complications, and predictors of 90-day mortality in neurologic patients with acute severe hypertension. Studying the Treatment of Acute hyperTension (STAT) was a multicenter (n=25) observational registry of adult critical care patients with severe hypertension treated with intravenous therapy. Emergency department or intensive care unit. A qualifying blood pressure measurement>180 mm Hg systolic or >110 mm Hg diastolic (>140/90 mm Hg for subarachnoid hemorrhage) was required for inclusion in the STAT registry. Patients with a primary neurologic admission diagnosis were included in the present analysis. All patients were treated with at least one parenteral (bolus or continuous infusion) antihypertensive agent. Of 1,566 patients included in the STAT registry, 432 (28%) had a primary neurologic diagnosis. The most common diagnoses were subarachnoid hemorrhage (38%), intracerebral hemorrhage (31%), and acute ischemic stroke (18%). The most common initial drug was labetalol (48%), followed by nicardipine (15%), hydralazine (15%), and sodium nitroprusside (13%). Mortality at 90 days was substantially higher in neurologic than in non-neurologic patients (24% vs. 6%, p<.0001). Median initial blood pressure was 183/95 mm Hg and did not differ between survivors and nonsurvivors. In a multivariable analysis, neurologic patients who died experienced lower minimal blood pressure values (median 103/45 vs. 118/55 mm Hg, p<.0001) and were less likely to experience recurrent hypertension requiring intravenous treatment (29% vs. 51%, p=.0001) than those who survived. Mortality was also associated with an increased frequency of neurologic deterioration (32% vs. 10%, p<.0001). Neurologic emergencies account for approximately 30% of hospitalized patients with severe acute hypertension, and the majority of those who die. Mortality in hypertensive neurologic patients is associated with lower minimum blood pressure values, less rebound hypertension, and a higher frequency of neurologic deterioration. Excessive blood pressure reduction may contribute to poor outcome after severe brain injury.

Effect of an Excess Intake of Casein Hydrolysate Containing Val-Pro-Pro and Ile-Pro-Pro in Subjects with Normal Blood Pressure, High-Normal Blood Pressure, or Mild Hypertension

A double-blind, placebo-controlled, randomized clinical trial was conducted to evaluate the effects of ingesting an excess of tablets containing casein hydrolysate, incorporating angiotensin I-converting enzyme (ACE) inhibitory peptides such as Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), in subjects with blood pressure ranging from normal to mild hypertension. A total of 48 subjects were given either 5 times more than the effective amount of casein hydrolysate or a placebo in tablet form for 4 weeks. In the active group, systolic blood pressure (SBP) decreased significantly as compared with the placebo group. In stratified analysis, however, this antihypertensive effect was not found in normotensive subjects. In addition, neither an acute or nor an excessive reduction in blood pressure nor clinically important adverse events were observed in this study. These findings suggest that intake of a 5-fold excess of tablets containing casein hydrolysate can lead to a mild improvement in hypertension without side effects.

Management of elderly hypertension from the aspect of geriatric medicine

The Japanese Society of Hypertension revised the guidelines for the management of hypertension in January 2009 (JSH2009). Regarding the target blood pressure (BP) in the elderly, we have set an intermediate target, less than 150/90 mmHg in patients aged ≥75 years with grade II or III hypertension (systolic BP≥160 mmHg) and the final target BP, less than 140/90 mmHg. Recent evidences such as HYVET, JATOS and CASE-J subanalysis consolidated these recommendations. In HYVET, the participants were aged ≥80 years, target control level of BP was <150/80 mmHg and achieved BP in the active-treatment group was 144/78 mmHg, not less than 140 mmHg in systolic BP. JATOS could not provide the evidence that strict control (<140 mmHg) would be more favorable to moderate control (140-159 mmHg) in prevention of cardiovascular events. CASE-J subanalysis in very elderly patients (≥75 years) demonstrated that an increased incidence of cardiovascular events was remarkable in cases controlled at ≥150/85 mmHg. The possible lower threshold of the BP levels that may cause J-shaped phenomenon is 120/60 mmHg which are indicated by the results of PATE-Hypertension and SHEP subanalysis. Subanalysis of Syst-Eur warned against reducing diastolic BP to <70 mmHg in patients with ischemic heart disease. Another important issue for suggesting lower threshold of BP is that an excessive reduction of BP may increase the risk of falling and faintness. More than 10% of bedridden patients are triggered by falling and fracture in Japan. In general, elderly hypertensive patients have a great risk of falling due to aging-related pathophysiological changes such as impaired autoregulation of cerebral blood flow and impaired baroreflex. Regarding the cognitive function, clinical evidences and basic research findings have provided the beneficial evidences of antihypertensive treatment even in the elderly patents. In conclusion, elderly hypertension should be treated aggressively with sufficient attention individually from the aspect of geriatric medicine. The Japanese Society of Hypertension revised the guidelines for the management of hypertension in January 2009 (JSH2009). Regarding the target blood pressure (BP) in the elderly, we have set an intermediate target, less than 150/90 mmHg in patients aged ≥75 years with grade II or III hypertension (systolic BP≥160 mmHg) and the final target BP, less than 140/90 mmHg. Recent evidences such as HYVET, JATOS and CASE-J subanalysis consolidated these recommendations. In HYVET, the participants were aged ≥80 years, target control level of BP was <150/80 mmHg and achieved BP in the active-treatment group was 144/78 mmHg, not less than 140 mmHg in systolic BP. JATOS could not provide the evidence that strict control (<140 mmHg) would be more favorable to moderate control (140-159 mmHg) in prevention of cardiovascular events. CASE-J subanalysis in very elderly patients (≥75 years) demonstrated that an increased incidence of cardiovascular events was remarkable in cases controlled at ≥150/85 mmHg. The possible lower threshold of the BP levels that may cause J-shaped phenomenon is 120/60 mmHg which are indicated by the results of PATE-Hypertension and SHEP subanalysis. Subanalysis of Syst-Eur warned against reducing diastolic BP to <70 mmHg in patients with ischemic heart disease. Another important issue for suggesting lower threshold of BP is that an excessive reduction of BP may increase the risk of falling and faintness. More than 10% of bedridden patients are triggered by falling and fracture in Japan. In general, elderly hypertensive patients have a great risk of falling due to aging-related pathophysiological changes such as impaired autoregulation of cerebral blood flow and impaired baroreflex. Regarding the cognitive function, clinical evidences and basic research findings have provided the beneficial evidences of antihypertensive treatment even in the elderly patents. In conclusion, elderly hypertension should be treated aggressively with sufficient attention individually from the aspect of geriatric medicine.

Rapid Blood Pressure Reduction in Acute Intracerebral Hemorrhage: Feasibility and Safety

The optimal blood pressure (BP) for treating acute intracerebral hemorrhage remains (ICH) uncertain. High BP may contribute to hematoma growth while excessive BP reduction might precipitate peri-hemorrhage ischemia. We examine here the feasibility and safety of reducing BP to lower than presently recommended levels in patients with acute ICH. Patients with ICH were prospectively randomized to standard BP treatment (mean arterial BP [MAP] 110-130 mmHg) or aggressive BP lowering (MAP < 110 mmHg) within 8 h of symptom onset. MAP was managed during the 48 h treatment period. NIHSS was obtained at baseline, 24, and 48 h. Brain CT was done 24 h after symptoms. A modified Rankin Scale (mRs) was obtained at 90 days. A clinical decline (NIHSS drop > or = 2 points) within the first 48 h was the primary endpoint. Hematoma enlargement at 24 h was a secondary endpoint. We enrolled 21 patients into each group. Mean age was 60.6 +/- 12.3 years and MAP on presentation was 147.6 +/- 18.2 mmHg. Treatment was started on average 3.2 +/- 2.2 h after symptom onset. Baseline clinical variables were identical between the 2 treatment groups. Target blood pressure was achieved within 87.1 +/- 59.6 min in the standard group and 163.5 +/- 163.8 min in the aggressive BP treatment group. There were no significant differences in early neurological deterioration, hematoma and edema growth, and clinical outcome at 90 days. A more aggressive reduction of acute hypertension after ICH does not increase the rate of neurological deterioration even when treatment is initiated within hours of symptom onset. Lowering BP aggressively did not affect hematoma and edema expansion but this possibility deserves further study.

Sleepers Versus Nonsleepers

There is growing evidence that an elevated nocturnal blood pressure is associated with an adverse cardiovascular outcome. In the Dublin Outcome Study, for each 10-mm Hg increase in mean nighttime systolic blood pressure, the mortality risk increased by 21%.1 At present, ambulatory blood pressure measurement is the only technique that permits close examination of the circadian profile and identification of patterns that may be associated with risk. Much happens to the cardiovascular system at nighttime, especially in relation to blood pressure. The patterns of nocturnal blood pressure–nocturnal hypertension, nocturnal hypotension, dipping and nondipping, reverse dipping, and autonomic failure–have been largely ignored in clinical practice. Many studies evaluating morbidity and dipping status have supported the concept that a diminished nocturnal blood pressure fall is associated with a worse prognosis.2 However, despite compelling evidence that changes in nighttime blood pressure may hold many secrets that, if unlocked, might benefit the clinical management of hypertension, there has been reluctance to focus on nocturnal blood pressure both clinically and in hypertension research.3 The nocturnal period of the 24-hour blood pressure profile, which is surprisingly complex, can be divided into a number of windows in which discrete phenomena may occur. These windows are the retiring (or perhaps more aptly named vesperal) window, the nighttime (or basal) window during which sleep is most likely, and the preawakening (or matinal) window, which precedes rising. In the normal individual there is a decline in blood pressure in the vesperal window from daytime levels of blood pressure to reach a plateau during the basal window (the “dipping” pattern), with a modest rise in the matinal window to regain daytime levels of blood pressure.4 In hypertensive patients (or …

Risers and Extreme‐Dippers of Nocturnal Blood Pressure in Hypertension: Antihypertensive Strategy for Nocturnal Blood Pressure

There is increasing evidence that disruption of diurnal blood pressure (BP) variation is a risk factor for hypertensive target organ damage and cardiovascular events. Especially, the risers (extreme non‐dippers), who exhibit a nocturnal BP increase compared with daytime BP, have the worst cardiovascular prognosis, both for stroke and cardiac events. On the other hand, extreme‐dippers (with marked nocturnal BP falls) are at risk for non‐fatal ischemic stroke and silent myocardial ischemia, particularly extreme‐dippers complicated with atherosclerotic arterial stenosis and excessive BP reduction due to antihypertensive medication. Extreme‐dipping status of nocturnal BP is closely associated with excessive morning BP surge and orthostatic hypertension. Hypertensive patients who have these conditions and exhibit marked BP variations are likely to have silent cerebral infarct and to be at high‐risk with regard to future stroke. Individualized antihypertensive medication targeting disrupted diurnal BP variation might thus be beneficial for such high‐risk hypertensive patients.

Risks and benefits of early treatment of acute myocardial infarction with an angiotensin-converting enzyme inhibitor in patients with a history of arterial hypertension: Analysis of the GISSI-3 database

Background Many trials have proved the benefits of early systematic treatment with angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction (AMI). Pathophysiological studies, however, suggest potential harm in excessive reduction of blood pressure (BP) in hypertensive patients with ischemic heart disease. Methods We analyzed data from the GISSI-3 (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico) trial to assess the effects of early treatment with angiotensin-converting enzyme inhibitors during AMI in patients with a history of hypertension compared with normotensive patients. The trial randomly assigned 19,394 patients to 6 weeks of lisinopril treatment or control, starting treatment within 24 hours of AMI onset. Results In the 10,661 normotensive patients, lisinopril significantly reduced lethal events, but in the 7362 hypertensive patients, a higher rate of lethal events was reported the first day of treatment, and the benefits only appeared subsequently. These results may be attributable to the subgroup of 1165 hypertensive patients with low baseline systolic BP (lower quintile, BP <120 mm Hg), in whom critical hypotension was more prone to develop after lisinopril treatment. In fact, these patients showed a higher mortality rate as the result of an excess of cardiogenic shock during the first day of lisinopril treatment (odds ratio 3.07, 95% CI 1.39-6.77) and a persistent, unfavorable death trend after 6 weeks. Conclusions These data suggest that caution should be exercised when using lisinopril in the acute phase of a myocardial infarction in patients with a history of hypertension but low systolic BP at presentation. (Am Heart J 2002;144:1018-25.)

Verapamil revisited: a transition in novel drug delivery systems and outcomes.

Verapamil, the oldest calcium-channel blocker, is now being rediscovered and reevaluated in the light of new novel drug delivery systems and new evidence-based trials. Verapamil, a phenylalkylamine, is useful in the treatment of hypertension, stable angina, and narrow QRS supraventricular arrhythmias. This calcium antagonist is effective in both young and old, and both black and white hypertensive patients, and is free of metabolic side effects. Verapamil has a well-documented history as an effective antianginal agent when directly compared with a beta-blocker, and is more effective in reducing myocardial ischemia compared with amlodipine monotherapy. Because of the short half-life of verapamil, drug delivery systems are used to prolong the duration of action. Novel drug delivery systems using encapsulated beads or a modified osmotic pump have been designed to be taken at nighttime to provide maximal blood pressure reduction in the early morning hours and effective 24-hour blood pressure control, and to avoid excessive blood pressure reduction during sleep. The Verapamil in Hypertension and Atherosclerosis Study has documented equivalent effectiveness of verapamil compared with chlorthalidone, but showed superior plaque regression and reduced events in subjects with the greatest plaques with verapamil treatment. The Angina Prognosis Study in Stockholm, comparing verapamil and metoprolol for stable angina, found no difference in total cardiovascular mortality or combined cardiovascular events. Other large ongoing randomized, multicenter trials, including Controlled-Onset Verapamil Investigation of Cardiovascular Endpoints and the International Verapamil-Trandolapril Study, will expand our knowledge of the role of verapamil in the treatment of hypertension.

Effect of nicardipine on cerebral blood flow in hypertensive patients with internal carotid artery occlusion: A PET study

The objective of this study was to elucidate the effect of intravenous administration of nicardipine on the cerebral blood flow of hypertensive patients with internal carotid artery occlusion (ICAO). Six patients with ICAO and 10 normal individuals were examined by positron emission tomography. The cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen, oxygen extraction fraction (OEF) and CBF/CBV ratio were evaluated for each vascular territory and each hemisphere, and the interhemispheric asymmetry index of each parameter was also calculated. Nicardipine was administered intravenously to each patient, and the changes in CBF (DeltaCBF%) and in blood pressure (DeltaBP) were examined. After the administration of nicardipine, the CBF was significantly increased in the patient hemisphere and was unchanged in the occluded hemisphere. Stepwise regression analysis disclosed that the DeltaBP and asymmetry index of OEF were significantly correlated with the DeltaCBF% in the occluded hemisphere. These results suggest that CBF is unchanged or increased in ICAO patients after nicardipine administration, but that excessive reduction of blood pressure may lead to CBF decrease in the patients with marked hemodynamic imbalance between the occluded and patent hemispheres. These results suggest that it is advisable not to reduce blood pressure excessively in these patients in the treatment of perioperative or acute hypertension with calcium antagonist.

Practical relevance of the 24-hour trough: peak ratio of antihypertensive drugs.

INTRODUCTION OF THE TROUGH:PEAK RATIO: The mean antihypertensive effect of a drug, measured just before the next dose in a multiple-dose regimen, is generally used as a criterion for approval by regulatory agencies. However, for many short-acting drugs very high doses may be required to maintain some antihypertensive activity at the end of the dosing interval. This may lead to an excessive reduction in blood pressure at the time of peak drug effect. In order to avoid unnecessarily large doses, regulatory agencies have introduced a new standard, the trough:peak ratio, which may be 50-60% but should should ideally be higher. BENEFITS OF HIGH TROUGH:PEAK RATIO: A high trough:peak ratio indicates a long duration of action. This may provide a better risk:benefit ratio compared to shorter acting antihypertensive agents by giving optimal therapeutic coverage for 24 h or even longer. Greater benefit may be gained from better control of overnight blood pressure, especially in the early morning hours when both a steep rise in blood pressure and a higher rate of cardiovascular events have been observed. Large swings in blood pressure may occur when the peak is too high in relation to the trough, increasing blood pressure variability, which may in turn increase target organ damage. A high trough:peak ratio may protect the patient against drug-induced blood pressure fluctuations. It may also produce fewer adverse effects as the blood pressure may fall further and the onset of action may be more gradual. This, together with an effective single daily dose, may increase patient compliance. Furthermore, an antihypertensive effect that lasts more than 24 h protects the patient against a rapid loss of blood pressure control when a dose is omitted or delayed. TROUGH:PEAK RATIO OF AVAILABLE ANTIHYPERTENSIVE DRUGS: We performed a literature survey to evaluate the practical relevance of the trough:peak ratio and to determine how it might help in the choice of antihypertensive agents. The results suggested that not all single daily doses of angiotensin converting enzyme inhibitors or calcium antagonists had a trough:peak ratio of > 50%. We conclude that specially designed, prospective clinical trials should be conducted to address this issue.

Brain Infarction Developed in Hypertensive and Normotensive Patients During Hospitalization—Hemodynamic Factors

To determine the effects of changes in blood pressure (BP) on the development of ischemic stroke, 17 patients who developed acute brain infarction during hospitalization were analyzed in relation to the vascular risk factors such as hypertension, previous stroke, diabetes mellitus, and hyperlipidemia. Their BPs were retrospectively referred to the onset of stroke. The average values of mean arterial blood pressure (MABP) on admission were 137 mmHg in hypertensive patients (HT; n = 9) and 101 mmHg in normotensives (NT; n = 8). HT patients received antihypertensive treatment after admission and MABP decreased by 22 mmHg (14%) prior to the ictus (three to sixty-five days after admission). MABP in NT patients remained constant before the attack (-1.4 mmHg, four to one hundred ten days after admission). Similarly, MABP decreased by 17 mmHg (four to ninety-three days) before the ictus in patients with previous stroke (n = 9), whereas it changed only a little in patients without history of stroke (n = 8). BP in each group elevated immediately after the stroke and gradually decreased to 90% of the resting level after two weeks. An excessive reduction of BP may induce brain infarction in HT or chronic stroke patients or cause it to recur.

ACE Inhibitors Drug Interactions of Clinical Significance

ACE inhibitors are used widely in the treatment of hypertension and congestive heart failure, but there is only limited information on adverse interactions between ACE inhibitors and other cardiovascular or noncardiovascular drugs. The present article provides an overview of this issue, with emphasis on those interactions having the greatest clinical implications. In patients who have been sodium and/or volume depleted by thiazide or loop diuretics, the additional use of ACE inhibitors can lead to an excessive reduction in blood pressure and symptomatic hypotension. An increase in serum potassium levels may occur after coadministration of potassium-sparing diuretics and ACE inhibitors, resulting in hyperkalaemia especially in patients with renal insufficiency. The incidence of acute renal failure may be associated with ACE inhibitor therapy when these drugs are combined with nonsteroidal anti-inflammatory agents and given to patients whose renal function becomes increasingly dependent on angiotensin II and prostaglandins. There is some evidence, albeit scant, linking ACE inhibitors with the induction of lithium toxicity in patients maintained on lithium, and with the occurrence of severe hypersensitivity reactions in patients undergoing haemodialysis, venom immunisation or concomitant allopurinol therapy.

Diagnostic value of electrocardiography and echocardiography for white coat hypertension in the elderly

Although white coat hypertension is common in clinical practice, 1–3 its pathogenesis and clinical prognosis remain unknown. In elderly patients with office hypertension, white coat hypertension should be differentiated from true hypertension, since the excessive reduction in blood pressure (BP) caused by antihypertensive medication may induce an ischemic event in a vital organ. The present study assesses the sensitivity and specificity of electrocardiography in detection of white coat hypertension and quantitatively measures left ventricular hypertrophy in such patients using echocardiography. Results are compared with those in normotensive control subjects and in patients with true persistent hypertension.

Ｊｕｍｂｌｉｎｇ現象を呈した片側突発生難聴例

A 45-year-old woman with hypertension developed tinnitus and a feeling of obstruction in her right ear after taking a new antihypertension drug. The next morning she complained of vertigo and hearing loss in her right ear. After ten days, the vertigo disappeared but Jumbling phenomenon was occurred. The patient could not walk without holding on to a handrail. Otoneurologic testing revealed unilateral hearing loss and bilateral vestibular disorder. We explained the importance of rehabilitation to the patient and gave instructions for exercising. After a few weeks she could walk alone.Although her equilibrium disorder was reduced, in otoneurologic test showed little improvement. Plasticity of the central nervous system seemed to have compensated for her disorder.A few cases of bilateral sudden hearing loss and bilateral vestibular neuronitis have been reported. They were thought to have been caused by virus infection, vascular disorder of the inner ear, syphilis, diabetes, cancer metastasis to the temporal bone, etc.We felt that the etiology in our patient was a vascular disorder of the inner ear due to an excessive reduction in blood pressure. This case emphasizes the importance of rehabilitation in nonacute vestibular disorders.

Effects of carvedilol on atrial natriuretic peptide, catecholamines, and hemodynamics in hypertension at rest and during exercise.

Possible counterregulatory neurohumoral and hemodynamic responses to carvedilol (a new vasodilating nonselective beta-receptor blocker) were studied in 19 men with essential hypertension (age range, 34-59 years; mean age, 44 years). Intra-arterial pressure, cardiac output (Cardio-green), heart rate, and the vasoactive peptides norepinephrine, epinephrine, and atrial natriuretic peptide (ANP) were measured at rest supine and sitting and during 100-W bicycle exercise before and 2 h after administration of 25 mg carvedilol. The same protocol was followed after 9 months of chronic carvedilol treatment (mean dose, 52 mg/day). Carvedilol induced both acute and chronic reductions (at rest supine, 11%) in mean arterial pressure, due in part to reduction in cardiac output (5%) and in part to reduction in total peripheral resistance (5%). At rest supine, carvedilol induced a reduction in ANP (27%) that could be viewed as a counterregulatory response to decrease in cardiac output, preventing excessive blood pressure reduction. ANP decreased (18%) when the patient sat up from the supine position and increased (67%) during exercise, but no further change was seen after acute or chronic carvedilol treatment. With the patient in the sitting position, norepinephrine was 110% higher than at rest supine; during 100-W exercise, norepinephrine increased 368%. A further increase (38-86% in the three situations, respectively) was seen after the first dose of carvedilol. Epinephrine showed similar but less marked changes. Neither extracellular fluid volume nor plasma volume (isotope dilution techniques) changed significantly during the study, but the acute blood pressure response to carvedilol was directly related to changes in extracellular fluid volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure during sleep: Antihypertensive medication

To investigate whether excessive reduction of blood pressure (BP) by antihypertensive medications correlates with myocardial infarction, especially during steep in elderly patients, we used telemetry and cuvette dye-dilution methods to assess the direct BP and the hemodynamics of 68 inpatients with essential hypertension during wakefulness and steep. There were 25 patients ≥60 years old (OH-group) and 43 were ≤59 years old (YH-group). Of the OH-group, 36% showed high BP during the day, with marked decreases (minimum BP <110/70 mm Hg) during steep. Average cardiac index (CI) of the OH-group was low during wakefulness and extremely low during show-wave sleep. Changes of mean BP in the OH-group correlated with changes in total peripheral vascular resistance index (TPRI) during steep, but this correlation was not observed in the YH-group. The antihypertensive effects on nocturnal BP of the various medications was: central adrenergic inhibitors ≤ β blockers with intrinsic sympathomimetic activity ≤ α (αβ) blockers ≤ angiotensin-converting enzyme inhibitors ≤ calcium antagonists. Because BP and CI were found to be very low and TPRI seems to play an important role in BP regulation in sleeping elderly patients, excessive antihypertensive medication may be harmful to this subgroup. However, because the effects on nocturnal BP differ among various antihypertensive treatments, further research is required on the relation between antihypertensive medication and the hemodynamics of sleeping elderly hypertensive patients.

Practical considerations in treating the elderly hypertensive patient

More than half of all older Americans die of cardiovascular diseases. Hypertension is a major risk factor for cardiovascular diseases, and its prevalence increases with age. Older patients are both at higher risk for end-organ complications and less likely than younger ones to survive such complications as myocardial infarction and stroke. Clinical studies have shown that reduction of elevated blood pressure is beneficial in many older persons. Optimal selection of antihypertensive therapy requires consideration of the special characteristics of the elderly, who differ from their younger counterparts in physiology, response to therapy and frequency of concomitant illnesses and medications. Calcium antagonists are particularly effective in these patients; other agents are useful in selected situations. Drugs that are likely to cause central nervous system side effects or orthostatic hypotension generally should be avoided in this patient population. Therapy should begin with a low dose and be titrated upward slowly, thus avoiding excessive reduction of blood pressure and the development of orthostatic hypotension. Treatment should be altered as necessary to minimize side effects that may impair quality of life or lead to poor compliance.

Individualized antianginal therapy guided by systemic arterial pressure

All antianginal drugs except nitrates are also first-line antihypertensive drugs. Their antianginal efficacy has not been evaluated in relation to pretreatment blood pressure. They may aggravate ischemia due to excessive reduction in blood pressure. Until the results of direct comparative studies are available, it is advisable to start treatment of angina pectoris in normotensive and hypotensive patients with other drugs that do not primarily decrease blood pressure. Nitrates are a reasonable choice.