Orthostatic hypotension and risk of cardiovascular disease in elderly people: the Rotterdam study. Comparative Efficacy of Yohimbine Against Pyridostigmine for the Treatment of Orthostatic Hypotension in Autonomic Failure Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. Effects of indomethacin on postural hypotension in Parkinsonism. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Lower limb and abdominal compression bandages prevent progressive orthostatic hypotension in elderly persons: a randomized single-blind controlled study. Effect of yohimbine on blood pressure in patients with depression and orthostatic hypotension induced by clomipramine Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Hypertension, orthostatic hypotension, and the risk of falls in a community-dwelling elderly population: the maintenance of balance, independent living, intellect, and zest in the elderly of Boston study. Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension. Potassium supplementation in the treatment of idiopathic postural hypotension. Orthostatic hypotension predicts incidence of heart failure: the Malmö preventive project.
OBJECTIVES To determine the prognostic role of orthostatic hypotension for cardiovascular disease ( CVD ) and all-cause mortality in elderly people . DESIGN Prospect i ve study . SETTING Community based . PARTICIPANTS Five thous and sixty-four subjects from the Rotterdam study aged 55 and older . MEASUREMENTS  Orthostatic hypotension  was measured using a Dinamap automatic blood pressure recorder . Orthostatic hypotension  is defined as a decline in systolic blood pressure of 20 mmHg or more or a decline in diastolic blood pressure of 10 mmHg or more from supine to st and ing position at any of three measurements taken 1 , 2 , and 3 minutes after st and ing . RESULTS At baseline , 901 subjects had  orthostatic hypotension  . During follow-up , 668 subjects had  coronary heart disease  ( CHD ) ( mean follow-up 6.0 + /- 3.5 years ) , and 1,835 subjects died ( mean follow-up period 7.8 + /- 3.8 years ) . Orthostatic hypotension increased the risk of CHD ( hazard ratio (HR)=1.31 , 95 % confidence interval (CI)=1.08 - 1.57 ) and all-cause mortality ( HR=1.22 , 95 % CI=1.09 - 1.36 ) , in models adjusted for age and sex . The risk was slightly lower after additional adjustment for cardiovascular risk factors . In analyses stratified for age , the HRs for all-cause mortality were 1.80 ( 95 % CI 1.25 - 2.60 ) , 1.13 ( 0.89 - 1.42 ) , and 1.27 ( 95 % CI=1.11 - 1.44 ) , in the first , second , and third tertile of age , respectively . CONCLUSION Orthostatic hypotension increases the risk of CHD and all-cause mortality in elderly people . The risk of CVD and mortality is strongest in younger and very old subjects Orthostatic hypotension affects patients with autonomic failure producing considerable disability because of presyncopal symptoms . Severely affected patients may have residual sympathetic tone that can be engaged to increase blood pressure ( BP ) with the & agr;-2 adrenergic antagonist yohimbine . This medication activates sympathetic outflow central ly and unrestrains norepinephrine release from noradrenergic neurons . Alternatively , the acetylcholinesterase inhibitor , pyridostigmine , can increase sympathetic tone by improving ganglionic cholinergic neurotransmission . Our purpose was to compare these complementary approaches and to explore whether the combination would lead to synergistic increases in BP . We compared the effects of 60 mg of pyridostigmine and 5.4 mg of yohimbine in a single-blind , r and omized , placebo-controlled , crossover fashion . In a subset of patients we tested the combination of pyridostigmine and yohimbine . Our primary outcome was the change in st and ing diastolic BP 60 minutes after drug administration from baseline . We studied a total of 31 patients with severe autonomic failure .  Yohimbine significantly improved st and ing diastolic BP as compared with placebo ( 11±3 mm Hg [ 95 % CI : 6 to 16 mm Hg ] ; P<0.001 ) . On the contrary , pyridostigmine did not increase the st and ing diastolic BP ( 0.6±3 mm Hg [ 95 % CI : −5 to 5 mm Hg ] ; P=0.823 ) . Only yohimbine showed a significant improvement in presyncopal symptoms .  Sixteen patients received the combination of pyridostigmine and yohimbine , but no evidence of synergistic pressor effect was found . Engaging residual sympathetic tone with yohimbine is a more effective approach to improve orthostatic hypotension as compared with pyridostigmine in patients with severe orthostatic hypotension OBJECTIVE To evaluate the efficacy of a 10-mg dose of midodrine 3 times per day in improving blood pressure ( BP ) and ameliorating symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension .  Midodrine hydrochloride , an alpha-agonist , could improve orthostatic BP by increasing vasomotor and venomotor tone . DESIGN / METHODS A total of 171 patients with orthostatic hypotension participated in a multicenter , r and omized , placebo-controlled study . They were r and omized to a 10-mg dose of midodrine or placebo 3 times per day in a 6-week study , comprising single-blind run-in ( at week 1 ) and washout at weeks 5 and 6 , with an intervening double-blind period ( weeks 2 to 4 ) . SETTING Twenty-five centers , with most patients evaluated in referral centers . MAIN OUTCOME MEASURES The primary end points were improvement in st and ing systolic BP , symptoms of lightheadedness , and a global symptom relief score ( by the investigator and patient separately ) . RESULTS Nine patients were not evaluable because of noncompliance or taking concomitant vasoactive medications ( 3 in the midodrine group , 6 in the placebo group ) . In the evaluable patients , midodrine result ed in improvements in st and ing systolic BP at all time points ( P<.001 at visits 2 , 3 , 4 , and 5 ) , in reported symptoms by the end of the second week of treatment ( P=.001 ) , and in the global symptom relief score rated by both the patient ( P=.03 ) and the investigator ( P<.001 ) . There was no effect by center , severity of orthostatic hypotension , use of fludrocortisone or compression garments , or diagnosis . The main adverse effects were those of pilomotor reactions , urinary retention , and supine hypertension . CONCLUSIONS Midodrine is efficacious and safe in the treatment of neurogenic orthostatic hypotension A study was conducted to evaluate the effect of indomethacin on orthostatic hypotension in Parkinsonism . Twelve elderly patients participated and the drug was given in two-ways -- as an intravenous infusion of 50 mg over 30 minutes and by mouth 50 mg thrice daily for six days . Results were assessed by measuring the degree of hypotension on st and ing , response to the cold pressor test , and forearm blood flow ( by strain-gauge plethysmography ) . Indomethacin significantly reduced the fall in blood pressure on st and ing ( P less than 0:001 ) and lessened or reversed orthostatic symptoms . Furthermore , there was an enhanced response to the cold pressor test and a reduction in forearm blood flow . These findings suggest that indomethacin has a positive effect on systemic vascular resistance Objective : To determine the best therapeutic strategy for the use of midodrine in patients with neurogenic orthostatic hypotension ( NOH ) . Background : Midodrine is a peripherally acting α-adrenergic agonist useful in the treatment of NOH . However , neither the most effective dosage of midodrine nor the required frequency of administration is established . Design / Methods : Midodrine dose-blood pressure response , pharmacokinetics , and duration of action were examined in a double-blind , placebo-controlled , four-way crossover trial . Twenty-five patients with NOH were r and omized to receive on successive days placebo or midodrine 2.5 , 10 , or 20 mg . Blood pressures of patients in the supine and st and ing positions were measured sequentially . A global assessment of the patient 's overall symptom improvement after each leg of the study was performed . Blood levels of midodrine and its active metabolite , desglymidodrine , were assayed . Results : Midodrine significantly increased st and ing systolic blood pressure , with the increase peaking at 1 hour . There was a significant linear relation between midodrine dosage and mean systolic blood pressure . The mean score for global improvement of symptoms was significantly higher for midodrine ( 10 and 20 mg ) compared with placebo . The half-life of desglymidodrine was ∼4 hours . Conclusion : A 10-mg dose of midodrine prescribed two to three times daily is effective in increasing orthostatic blood pressure and ameliorating symptoms in patients with NOH PURPOSE To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure . PATIENTS Ninety-seven patients with orthostatic hypotension were r and omized in a 4-week , double-blinded , placebo-controlled study with a 1-week placebo run-in period . Patients ranged in age from 22 to 86 years ( mean : 61 years ) . METHODS After a 1-week run-in phase , either placebo or midodrine at a dose of 2.5 mg , 5 mg , or 10 mg was administered three times a day for 4 weeks . Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase . The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the design ated dose was reached . Efficacy evaluations were based on an improvement at 1-hour postdose in st and ing systolic blood pressure and in symptoms of orthostatic hypotension ( syncope , dizziness/lightheadedness , weakness/fatigue , and low energy level ) . RESULTS Midodrine ( 10 mg ) increased st and ing systolic blood pressure by 22 mm Hg ( 28 % , p < 0.001 versus placebo ) . Midodrine improved ( p < 0.05 ) the following symptoms of orthostatic hypotension compared to placebo : dizziness/lightheadedness , weakness/fatigue , syncope , low energy level , impaired ability to st and , and feelings of depression . The overall side effects were mainly mild to moderate . One or more side effects were reported by 22 % of the placebo group compared with 27 % of the midodrine-treated group . Scalp pruritus/tingling , which was reported by 10 of 74 ( 13.5 % ) of the midodrine-treated patients , was most frequent . Other reported side effects included supine hypertension ( 8 % ) and feelings of urinary urgency ( 4 % ) . CONCLUSION We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure OBJECTIVES This study sought to assess the efficacy of compression b and age of legs and abdomen in preventing hypotension and symptoms . BACKGROUND Progressive orthostatic hypotension can occur in elderly people during st and ing . METHODS Twenty-one patients ( 70 + /- 11 years ) affected by symptomatic progressive orthostatic hypotension underwent 2 tilt-test procedures , with and without elastic b and age of the legs ( compression pressure 40 to 60 mm Hg ) and of the abdomen ( compression pressure 20 to 30 mm Hg ) in a r and omized crossover fashion . Leg b and age was administered for 10 min and was followed by an additional abdominal b and age for a further 10 min . Symptoms were evaluated by a 7-item Specific Symptom Score ( SSS ) question naire before and after 1 month of therapy with elastic compression stockings of the legs ( prescribed in all patients irrespective of the results of the tilt study ) . RESULTS In the control arm , systolic blood pressure decreased from 125 + /- 18 mm Hg immediately after tilting to 112 + /- 25 mm Hg after 10 min of sham leg b and age and to 106 + /- 25 mm Hg after 20 min despite the addition of sham abdominal b and age . The corresponding values with active therapy were 129 + /- 19 mm Hg , 127 + /- 17 mm Hg ( p = 0.003 vs. control ) , and 127 + /- 21 mm Hg ( p = 0.002 vs. control ) . In the active arm , 90 % of patients remained asymptomatic , versus 53 % in the control arm ( p = 0.02 ) . During the month before evaluation , the mean SSS score was 35.2 + /- 12.1 with dizziness , weakness , and palpitations accounting for 64 % of the total score . The SSS score decreased to 22.5 + /- 11.3 after 1 month of therapy ( p = 0.01 ) . CONCLUSIONS Lower limb compression b and age is effective in avoiding orthostatic systolic blood pressure decrease and in reducing symptoms in elderly patients affected by progressive orthostatic hypotension Orthostatic hypotension , one of tricyclic antidepressant treatment 's side effects , is also a factor in limiting adequate antidepressant dosing . We tested in a double‐blind , crossover , placebo‐controlled study the effect of low doses ( 4 mg/t.i.d . ) of yohimbine in 12 patients with depression with ciomipramine‐induced orthostatic hypotension .  Yohimbine , a selective α2‐adrenoceptor antagonist , had a favorable effect in orthostatic hypotension and induced a significant increase in blood pressure . A pharmacodynamic and pharmacokinetic interaction between yohimbine and clomipramine or demethylclomipramine was discussed BACKGROUND Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension ( OH ) but it significantly worsens supine hypertension . By enhancing ganglionic transmission , pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension . OBJECTIVE To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide , alone or in combination with a subthreshold ( 2.5 mg ) or suprathreshold ( 5 mg ) dose of midodrine hydrochloride , compared with placebo . DESIGN We report a double-blind , r and omized , 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH . A total of 58 patients with neurogenic OH were enrolled . After 1 day of baseline measurements , patients were given 4 treatments ( 3 active treatments [ 60 mg of pyridostigmine bromide ; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride ; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride ] and a placebo ) in r and om order on successive days . Blood pressure ( BP ) and heart rate were measured , both supine and st and ing , immediately before treatment and hourly for 6 hours after the treatment was given . RESULTS No significant differences were seen in the supine BP , either systolic ( P = .36 ) or diastolic ( P = .85 ) . In contrast , the primary end point of the fall in st and ing diastolic BP was significantly reduced ( P = .02 ) with treatment . Pairwise comparison showed significant reduction by pyridostigmine alone ( BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo ; P = .04 ) and pyridostigmine and 5 mg of midodrine hydrochloride ( BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo ; P = .002 ) . St and ing BP improvement significantly regressed with improvement in OH symptoms . CONCLUSIONS Pyridostigmine significantly improves st and ing BP in patients with OH without worsening supine hypertension . The greatest effect is on diastolic BP , suggesting that the improvement is due to increased total peripheral resistance OBJECTIVES To investigate the relationships between uncontrolled and controlled hypertension , orthostatic hypotension ( OH ) , and falls in participants of the Maintenance of Balance , Independent Living , Intellect , and Zest in the Elderly of Boston Study ( N=722 , mean age 78.1 ) . DESIGN Prospect i ve population -based study . SETTING Community . PARTICIPANTS Seven hundred twenty-two adults aged 70 and older living within a 5-mile radius of the study headquarters at Hebrew Rehabilitation Center in Boston .  MEASUREMENTS Blood pressure ( BP ) was measured at baseline in the supine position and after 1 and 3 minutes of st and ing .  Systolic OH ( SOH ) and diastolic OH at 1 and 3 minutes were defined as a 20-mmHg decline in systolic BP and a 10-mmHg decline in diastolic BP upon st and ing . Hypertension was defined as BP of 140/90 mmHg or greater or receiving antihypertensive medications ( controlled if BP < 140/90 mmHg and uncontrolled if ≥ 140/90 mmHg ) . Falls data were prospect ively collected using monthly calendars . Fallers were defined as those with at least two falls within 1 year of follow-up . RESULTS OH was highest in participants with uncontrolled hypertension ; SOH at 1 minute was 19 % in participants with uncontrolled hypertension , 5 % in those with controlled hypertension , and 2 % in those without hypertension ( P ≤ .001 ) ) . Participants with SOH at 1 minute and uncontrolled hypertension were at greater risk of falls ( hazard ratio=2.5 , 95 % confidence interval = 1.3 - 5.0 ) than those with uncontrolled hypertension without OH . OH by itself was not associated with falls . CONCLUSION Older adults with uncontrolled hypertension and SOH at 1 minute are at greater risk for falling within 1 year . Hypertension control , with or without OH , is not associated with greater risk of falls in older community-dwelling adults PURPOSE In this double-blind study , the authors compared the safety and efficacy of the investigational oral agent midodrine , a specific alpha 1-sympathomimetic agent , with ephedrine , a nonspecific alpha- and beta-adrenergic receptor agonist . Eight patients ( 4 men and 4 women ) with refractory orthostatic hypotension result ing from autonomic failure were studied . This study was based on the notion that neurogenic orthostatic hypotension results from attenuation of adrenergic nerve traffic and not from alpha-adrenergic receptor dysfunction . Although arteriolar vasoconstrictors seem to be appropriate therapeutic agents , their success has been limited , and the search for an ideal drug is ongoing . METHODS The authors employed a blocked , double-blind , r and omized crossover design . The single-blind placebo run-in period was 2 days . The double-blind titration period with either midodrine or ephedrine was 3 to 5 days ; the titration end point was to increase st and ing systolic blood pressure to > or = 80 mm Hg and to maintain a supine pressure below 180/100 mm Hg . The maintenance period was 3 to 5 days . A 4-day placebo washout period was interposed at the crossover point . RESULTS The ability to st and improved in patients treated with midodrine but not with ephedrine . Midodrine significantly increased both systolic ( P < 0.001 ) and diastolic ( P < 0.001 ) st and ing blood pressure over placebo ( P < 0.001 ) and ephedrine ( P < 0.05 ) . In contrast , ephedrine-induced changes in st and ing pressures did not significantly differ from placebo ( P > 0.05 ) . Midodrine treatment improved the frequency of the ability to st and as compared with ephedrine , and was associated with a significantly higher incidence of st and ing systolic pressures > 80 mm Hg than was placebo ( P < 0.001 ) . Both midodrine and ephedrine significantly increased supine systolic and diastolic blood pressures over placebo ( P < 0.001 , P < 0.01 , P < 0.01 , P < 0.01 , respectively ) , but were not significantly different from each other . Ephedrine significantly increased ( P < 0.05 ) the pulse rate as compared with placebo and midodrine , whereas midodrine produced a statistically significant ( P < 0.05 ) but clinical ly minimal decrease in pulse rate compared with placebo . Neither drug affected clinical laboratory variables . CONCLUSIONS Midodrine safely and effectively improved orthostatic hypotension caused by autonomic failure . Our data suggest that the ability to st and is improved better by midodrine than by ephedrine We studied the effects of potassium supplementation ( 60 mmol/day ) and matching placebo on the postural blood-pressure fall in ten elderly patients with symptomatic idiopathic postural hypotension in a double-blind , r and omized cross-over trial . There was a significant decrease in the orthostatic fall in systolic blood pressure ( SBP 33 + /- 5 mmHg to 16 + /- 9 mmHg , p less than 0.01 ) and in supine SBP ( 162 + /- 7 to 150 + /- 7 mmHg , p less than 0.01 ) between placebo and potassium phases . Supine diastolic and erect blood pressures were unchanged , though pulse rate showed a greater orthostatic increase ( 7 + /- 3 beats/min to 14 + /- 2 beats/min , p less than 0.05 ) following potassium therapy . No significant changes were seen in intracellular electrolytes , plasma renin activity , aldosterone levels or body weight . Seven patients reported symptomatic improvement with potassium , but none during the placebo phase . Potassium therapy was well tolerated and may be a successful and safe method of treating idiopathic postural hypotension BACKGROUND The presence of orthostatic hypotension ( OH ) predicts all-cause mortality and incident cardiovascular disease . Whether or not OH is associated with the development of  heart failure ( HF )  remains unknown . METHODS In this Swedish population -based prospect i ve study ( the Malmö Preventive Project ) , the incidence of HF in relation to baseline OH , defined as decrease in systolic ( SBP ) ≥20 mm Hg and /or diastolic blood pressure ( DBP ) ≥10 mm Hg upon st and ing , was studied in 32,669 middle-aged individuals ( 68.2 % men ; mean age , 45.6 ± 7.4 years ) over a mean follow-up period of 24 years . RESULTS At baseline , 1,991 ( 6.1 % ) participants were found to have OH . During follow-up , 1,293 persons ( 4.0 % , mean age at presentation : 67.9 ± 7.9 years ) were hospitalized for HF , 912 ( 2.8 % ) of whom without previous or concurrent myocardial infa rct ion ( MI ) ( " nonischemic HF " ) . Among those who had OH , the corresponding numbers were 6.5 % ( n = 129 ) and 4.6 % ( n = 92 ) , respectively . In multivariable Cox proportional hazard models , taking conventional HF risk factors into account , OH was associated with both all-cause and " nonischemic " HF events ( hazard ratio ( HR ) : 1.22 , 1.01 - 1.46 , and 1.31 , 1.05 - 1.63 , respectively ) . The association between OH and HF was more pronounced in younger ( aged < 45 years ) than older individuals ( 2.05 ; 1.31 - 3.22 vs. 1.12 , 0.92 - 1.38 , respectively , P < 0.001 for interaction between age and OH on incident HF ) . CONCLUSIONS The presence of OH among middle-aged adults  predicts long-term incidence of HF hospitalizations independently of conventional risk factors . Our findings add to the available data indicating that OH is a potential independent cardiovascular risk factor , especially with regard to younger individuals and nonischemic HF
BACKGROUND orthostatic hypotension ( OH ) affects up to 30 % of adults over 65 and frequently contributes to falls and syncopal episodes .
Current guidelines suggest a wide range of treatments , but systematic review s of the evidence base for such recommendations are lacking .
METHODS we performed a systematic review to assess the evidence for all non-pharmacological and pharmacological interventions for OH .