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Primary Care Corner: Initial orthostatic hypotension and adverse outcomes

3 Aug, 17 | by

by Geoffrey Modest MD

Yet another article came out indicating that initial orthostatic hypotension, measured immediately after standing, had a strong association with dizziness as well as long-term adverse outcomes measurement (see doi:10.1001/jamainternmed.2017.2937).



— cohort study of 11,429 participants in the Atherosclerosis Risk in Communities Study (1987-1989)

— mean age 54, 54% women, 26% black/74% white, blood pressure 120/73, heart rate 67, eGFR 102, BMI 27, diabetes 11%, hypertension 33% and 28% taking meds with in the past 2 weeks, 5% coronary heart disease, 2% stroke, heart failure 4%, dizzy on standing 10%, diuretics 16%, alcohol never used 24%/former 18%/current 58%, smoking never 41%/former 33%/current 26%

— orthostatic hypotension (OH) was defined as a drop in systolic blood pressure of at least 20 mmHg, or diastolic at least 10 mmHg when going from supine to standing position, after initially lying down for 20 minutes. Blood pressure was measured 5 times at 25 second intervals after standing.

— Primary outcome: association of these 5 OH measurements and history of dizziness on standing; as well as risk of fall, fracture, syncope, motor vehicle crashes, and all-cause mortality over a median of 23 years of follow-up

–Covariates included age, sex, race/research center (e.g. white people from Washington County, Maryland, Minneapolis, Minnesota and Forsyth, North Carolina; black people from Jackson, Mississippi, and Forsyth, North Carolina), heart rate, BMI, eGFR, diabetes, hypertension, alcohol use, education level, smoking status, physical activity, coronary heart disease, history of stroke, heart failure, hypertension medications in the past 2 weeks, diuretic use, antidepressant use, sedative use, hypnotic use, antipsychotic medication use, anti-cholinergic medication use, resting SBP, resting DBP, and pulse pressure

–OH measurement 1 was 28 seconds after standing, measurement 2 was after 53 seconds, 3 after 76 seconds, 4 after 100 seconds, 5 after 116 seconds (ie last measurement was at about 2 minutes after standing)



— OH measurement 1 was the only measurement associated with a higher odds of dizziness, OR 1.49 (1.18-1.89), was found in 13.5% of people, and was associated with the greatest drops in SBP (dizziness beginning around 20mmHg drop in SBP and increasing with further drops) or DBP (beginning around 5mmHg drop and increasing with further drops​)

— OH measurement 1 was associated with the highest rates of subsequent fracture (18.9 per 1000 person-years), syncope (17.0 per 1000 person-years) and death (31.4 per 1000 person-years)

— OH measurement 2 was associated with the highest rate of falls (13.2 per 1000 person-years) and motor vehicle crashes (2.5 per 1000 person-years)

— after adjustment for covariates:

— OH measurement 1 was significantly associated with the risk of fall (22% increase), fracture (16% increase), syncope (40% increase), and mortality (36% increase)

​– OH measurement 2 was associated with all long-term outcomes including 29% increase in falls, 14% increase in fracture, 36% in syncope,  43% increase in motor vehicle crashes, 42% increased mortality

— measurements obtained after 1 minute were not associated with dizziness and were inconsistently associated with any of the long-term outcomes.



–this study fits in well with prior studies finding a high prevalence of initial OH , specifically an Irish study comparing initial orthostatic hypotension within 15 seconds of standing and typical OH after 3 minutes of standing: typical OH was found in 6.9% of the population, but initial OH was found in 32.9% in those over 50yo

–this study was impressive in that it did so many BP measurements, then found that the measurements done within 30 seconds after standing were best correlated with dizziness and checking after 60 seconds did not seem to add much.  this makes it much easier in primary care practice: check the blood pressure a couple of times right after the patient stands, instead of waiting longer

–but, there are some important limitations to the study:

–they did not measure and cannot comment specifically on later BP measurements (eg after 3 minutes for the standard definition of orthostatic hypotension; this OH may be related to defects in the renin-angiotensin system response, as opposed to initial OH which may reflect more the immediate neural arterial baroreceptor control of sympathetic vasomotor response leading to increased vascular resistance and to changes in splanchnic capacitance vessels)

–they had patients lie down for 20 minutes prior to assessing OH, a likely non-reproducible condition in a busy primary care practice

–they cannot attribute causation in a study like this: is it the OH, or the underlying autonomic dysfunction leading to OH, that leads to the long-term adverse outcomes?

–but, there are also some reasonable inferences/conclusions:

–initial orthostatic hypotension is really common (as per other studies)

–often there is no reported dizziness, though the reports of dizziness do increase as the blood pressure decreases greater amounts

–there are real long-term important clinical associations of initial OH, and many of them are likely related to the OH itself (falls/fractures, syncope/presyncope, and perhaps motor vehicle accidents)

–other studies have found association in elderly with baseline cognitive impairment, even mild, and  increased cognitive impairment with lower SBP (see  )

–there are some reasonable interventions available to decrease initial OH: backing off on the intensity of blood pressure meds if the patient is on them, avoiding meds that are associated with falls, prescribing compression stockings, high potato chip diet (ie, lots of salt, when appropriate for the patient), or using drugs such as midodrine and fludrocortisone.

so, my practice and results, from seeing lots of older people and from checking initial orthostatics regularly since I became aware of initial OH about 5 years ago, confirms that initial OH is quite common, dizziness is often not reported, and when I find initial OH I do back off on meds that decrease blood pressure, and even use the other methods above including given fludrocortisone and/or midodrine. Given my busy practice, I just have the patient sit on the exam table for several minutes, often starting to see another patient or doing paperwork (and, by the way, my manual readings after the patient sits a couple of minutes can be 20-30 mmHg lower than right after getting up on the table), then I ask the patient to stand and I check the blood pressure 2-3 times over the next minute.  And, I usually find that the blood pressure decreases right away and typically increases after about 30 seconds (consistent with the above study). One additional reason that I am pretty aggressive in addressing the initial OH is that I am concerned that a significant drop in blood pressure in the office might be even more so at home, perhaps exacerbated by some dehydration in the heat, or diarrhea, etc, and that this could lead to an even higher likelihood of falls (untested hypothesis, but does fit under the general rubric of “doing no harm” ….).


Primary Care Corner with Geoffrey Modest MD: Fludrocortisone for Vasovagal Syncope

22 Sep, 16 | by EBM

By Dr. Geoffrey Modest

Vasovagal syncope is pretty common, but there are no documented effective treatments. Fludrocortisone has potential by improving venous return: its efficacy was evaluated in the Prevention of Syncope Trial 2 — POST 2 trial (see Sheldon R. JACC 2016; 68: 1).


  • 210 patients (71% female, median age 30, BMI 24, HR 70 bpm, BP 112/70) with a mean of 15 syncopal episodes over 9 years
  • Randomized to fludrocortisone at the highest tolerated doses (from 0.05-0.2 mg/d, titrated over 2 weeks, with most achieving the 0.2  mg dose) vs placebo and followed for 1 year
  • Inclusion criteria: >13 yo, >2 lifetime syncopal episodes; exclusions: diabetes, hepatic disease BP>135/85, “significant comorbidities”, or if when standing 5 minutes they had postural tachycardia of >30 bpm, or orthostatic hypotension of >20/10 mmHg.


  • 96 patients had at least 1 syncopal episode
  • Overall there was a 31% marginally non-significant reduction in syncope in those on fludrocortisone [HR 0.69 (0.46-1.03), p=0.069]: 44.0% vs 60.5%. the most benefit was in those with systolic BP<110, BMI>20, and syncope frequency >7/yr
  • But, in multivariable model, fludrocortisone conferred a significant 37% decrease [HR 0.63 (0.42-0.94), p=0.024]
  • And, when analysis was restricted to being on the fludrocorisone after dose stabilization, there was an even more significant 49% decrease [HR 0.51 (0.28-0.89), p=0.019]: approx 60% vs 30% in those achieving the 0.2 mg dose


  • There are a myriad of etiologies for syncope to consider, especially cardiac or neurologic (all excluded in the above study). And the preferred treatment for the syncope is to treat the underlying condition.
  • The above applies to those with classic “fainting” episodes: vasovagal syncope, which can happen even in patients with underlying cardiac or neuro morbidities, often triggered by stress, noxious stimuli, anxiety (including venipuncture, blood donation), prolonged standing or sitting, heat exposure, exertion, orthostasis,  (and in older people can be associated with micturition, defecation, cough), and clinically associated with the typical prodrome of light-headedness, along with vagal symptoms of nausea, pallor, diaphoresis. Symptoms typically gets better with lying down, though there can be some residual fatigue. And there can be brief episodes of myoclonic/involuntary esp. limb movements. But there should be no post-ictal state
  • Fludrocortisone seemed pretty effective when at the 0.2 mg dose, and likely more effective than midodrine (a few small studies finding effectiveness but less impressively)
  • Fludrocortisone has been used effectively in those with autonomic failure and orthostatic hypotension, presumably from its increased renal sodium absorption and plasma volume expansion.
  • In my experience, fludrocortisone is very well-tolerated in fragile patients with multiple comorbidities: I have prescribed fludrocortisone (sometimes with midodrine) very effectively in my reasonably large group of older patients with orthostatic hypotension, presumably from autonomic dysfunction (workup otherwise negative, or perhaps some diabetes, but often just from aging…). In this young group in the study above, without comorbidities and with just vasovagal syncope, there were no serious adverse events. And for those with orthostatic hypotension, of course, caffeine helps (1-3 cups of coffee/d, or 2-5 cups of tea). And, though I have not used them, NSAIDs can also help when used with fludrocortisone.
  • So, bottom line: vasovagal syncope is common (overall about 20-35% of syncope causes), a pretty high % (up to 34% in one study) have no warning symptoms prior to syncope, and can be associated with bad accidents (e.g., car crashes), so the above study may really prove to be clinically useful. One wonders if using the max dose of 0.3 mg might be even more useful, and I do have several elderly patients tolerating this dose well)

Primary Care Corner with Geoffrey Modest MD: Orthostatic hypotension

18 Dec, 14 | by EBM

By: Dr. Geoffrey Modest

Circulation had an article on the prevalence of orthostatic hypotension in Ireland (see doi:10.1161/CIRCULATIONAHA.114.009831​). This study involved 4475 community-based people over age 50 from a nationally representative cohort study (TILDA — The Irish Longitudinal Study on Ageing — that’s how they spell “aging”…), recording blood pressure and pulse response to standing. They looked at initial orthostatic hypotension, defined as a BP decrease of >40 mmHg systolic or >20 mmHg diastolic within 15 seconds of standing and associated with symptoms of cerebral hypoperfusion, and typical orthostatic hypotension, defines as a BP decrease of >20 mmHg in systolic or >10 mmHg in systolic after 3 minutes of standing.


–Cohort baseline characteristics: average age 62.8, 51.8% female, 19% smokers, 7.5% diabetes, 34.5% hypertensive, total of <11% with any cardiovascular history — so pretty healthy

–Initial orthostatic hypotension in 32.9% of those >50yo, no difference by age or gender

–Typical orthostatic hypotension in 6.9% overall, increasing from 4.2% in 50 yo to 18.5% in those >80yo

–Prevalence of failure to return to baseline blood pressure after standing 40 seconds increased with age: from 9.1% in 50 yo to 41.2% in those >80yo

So, a few points.

  1. The pathophysiology and epidemiology of initial orthostatic hypotension is somewhat different from the typical orthostatic hypotension. With initial orthostatic hypotension, there is a rapid temporal mismatch between cardiac output and vascular resistance. This typically happens in thin young people (who need to dangle their legs prior to getting out of bed, for example) and those on a-blockers (including reports with tamsulosin for BPH). The typical orthostatic hypotension results from standing, pooling of blood in the legs, decreased venous return, which usually triggers a baroreceptor reflex inducing vasoconstriction (so the the usual change is a decrease of about 5 mmHg systolic and a slight increase in diastolic, which rapidly reverses with rapid vasoconstriction). but without this vasoconstriction, there is subsequent decrease in cardiac output and hypotension. This tends to happen in older people who have diminished baroreceptor responsiveness, and in those with hypovolemia, on aggressive diuretics, tricyclic antidepressants, etc.
  2. I don’t want to overinterpret this study. The population studied was racially and ethnically pretty uniform. There was no information on whether there was a difference if they had underlying hypertension or what medications they were taking​. and there are no data on whether the typical orthostatic hypotension was symptomatic. And the limited data available do not all point to asymptomatic hypotension as a cause of falls, for example. BUT, to me, these numbers are very impressive. I do typically check orthostatics on my elderly patients and very often do find marked hypotension on standing, sometimes symptomatic and sometimes not. when the patient is symptomatic (either by history at home, eg when standing, or in the office), I do not hesitate to back off on BP meds (or if they are not on them, I sometimes need to use fludrocortisone and high salt diets to raise the blood pressure). in asymptomatic patients, the decision is harder. In general, I am pretty concerned that they may have an even more exaggerated hypotensive orthostatic response if they are a little dehydrated (hot summer day), or don’t drink their usual amounts of fluids, or even postprandially, when blood pressure tends to be lower. It is also impressive that symptomatic initial orthostatic hypotension happens in about 1/3 of the patients over 50 yo. So, seems reasonable to ask specifically about that, as well as falls…

So, my approach is that if the blood pressure really drops on standing (eg a systolic less than 120), I do back off on blood pressure meds even if the patient is asymptomatic. Given the lack of data in the elderly that a lower systolic is beneficial (perhaps because the studies did look at lower blood pressures, leading JNC8 to suggest a target of 150/90), seems like the better part of valor to back off on blood pressure meds.

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