Initial orthostatic hypotension and adverse outcomes

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). 

Details:

-- 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)

Results:

-- 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.

Commentary:

--this study fits in well with prior studies finding a high prevalence of initial OH, reviewing 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 

    --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” ….).