orthostatic hypotension and dementia

Orthostatic hypotension in the elderly may be associated with incident dementia (see htn orthostatic and cognitive impair eurheartj2018 in dropbox, or doi.org/10.1093/eurheartj/ehy418).

Details:

--Analysis of 2316 patients in the Hypertension in the Very Elderly Trial (HYVET) cohort, a double-blind study of hypertensive patients ≥80 years, randomized to indapamide 1.5mg sustained release (long-acting thiazide-like diuretic) with optional addition of the ACE-I perindopril 2-4mg. (see htn elderly HYVET nejm 2008 in dropbox for access to HYVET)

--from 90 primary and secondary centers in 13 countries

--all patients had no clinical diagnosis of dementia, mean SBP of 160-199 mmHg and standing SBP ≥ 140 mmHg

    --mean age 83.6, 60% female, mean sitting BP 173/91 mmHg, followed mean of 2.0  years;

    --study found large reductions in stroke, death from any cause, death from cardiovascular causes, and rate of heart failure

--cognitive function assessed by the Mini-Mental State Exam (MMSE), done annually.

--Orthostatic hypotension (OH): fall of ≥15 mmHg in systolic and or ≥7 mmHg in diastolic pressure after 2 min standing from a sitting position.

--Subclinical orthostatic hypotension with symptoms (SOH): a fall  less than OH but with unsteadiness, light-headedness, or faintness in the week before blood pressure measurement

--significant reduction in cognitive function: a reduction of MMSE below a score of 24 or by more than 3 points triggered a dementia assessment, as defined by DSM-IV [mean MMSE at baseline was 25]

--those with OH tended to have a higher sitting systolic BP (174.5 vs 173.3 mmHg) and lower standing systolic and diastolic (162.0/82.8 vs 169.3/89.9z); were minimally older (83.9 vs 83.5 yrs); had lower MMSE at baseline (24.5 vs 25.4)

Results:

--Orthostatic hypotension (n=538):

    -- 36% increased risk of cognitive decline (906 events), hazard ratio (HR) 1.36 (1.14–1.59)

    -- 34% increased risk of incident dementia (241 events), HR 1.34 (0.98–1.84). When risk of cardiovascular events was included, results were significant with HR 1.39 (1.19–1.62) and HR 1.34 (1.05–1.73), respectively.

    -- during study follow-up there were 315 incident OH cases: 169 in the placebo and 146 in the actively treated group: the realtionship between OH and incident dementia still was statistically signficant

    -- also no difference in outcome if look at those with baseline MMSE >26

    ​-- these relationships between OH and cognitive decline were found particularly in those, where a 10 mmHg fall in DBP was associated with a26% increase in cognitive decline

    -- there was no relationship between OH and mortality or cardiovascular outcomes as individual outcomes

-- Subclinical orthostatic hypotension (n=105):

    -- 56%  increased risk of cognitive decline HR 1.56 (1.12–2.17)

    -- 79% increased risk of dementia HR 1.79 (1.00–3.20)

    -- SOH was associated with 2-3 times the risk of cardiovascular events, HR 2.28 (1.25-4.14), and mortality, HR 2.97 (1.76-5.01)

--Combining the results from the HYVET cohort in a meta-analysis with the existing published literature for the Rotterdam Study, the 3 City Study, the Malmo Study and the Swedish Good Aging in Skane Study found a 21% (9–35%) increased risk of dementia with OH.

Commentary:

--there have been several articles recently highlighting initial orthostatic hypotension (vs the more commonly measured one found after 2-3 minutes), noting that initial OH is much more common than the subsequent one, and is associated with lots of clinical problems over 23 years of followup, such as increased falls, fractures, syncope, motor vehicle crashes, and overall increased mortality (see http://gmodestmedblogs.blogspot.com/2017/08/initial-orthostatic-hypotension-and.html ). other studies noted in this blog have shown increased cognitive impairment in a cohort with baseline cognitive impairment, though some other studies have not found cognitive impairment

--as a complicating issue, a recent study found that aging was associated with significant decreases in blood pressure, reinforcing the importance of continuing to assess blood pressure over time and probably adjust BP meds accordingly (see http://gmodestmedblogs.blogspot.com/2018/01/decreasing-blood-pressure-in-elderly.html )

--as an aside, there are several articles finding that blood pressure variability is associated with an increase in cardiovascular events (see http://gmodestmedblogs.blogspot.com/2016/09/blood-pressure-variability-increases.html for an meta-analysis on this). are the clinical bad events with OH, or even initial OH, a reflection of increased blood pressure variability?

--older adults are at increased risk of OH due to impaired compensatory mechanisms, including decreased baroreceptor (pressure) sensitivity, increased arterial stiffness, and reduced parasympathetic tone​

--This is also particularly relevant to older adults and those with hypertension in whom cerebral auto-regulatory mechanisms may be less able to adapt

--it is a bit unclear why the relationship with cognitive decline was stronger with DBP than SBP, though inclusion criteria in HYVET were centered around SBP with standing SBP >140, and DBP was not considered, leading to perhaps wide ranges of DBPs and a false attribution

-- the inclusion of the meta-analysis helps validate the HYVET results, by including data from studies with longer follow-up and in different populations.

--it is important to remember that this study was ultimately a post-hoc analysis of the HYVET trial and cannot determine causality (was it the OH leading to cognitive decline?, or the fact that this subgroup with OH had more blood pressure variability, stiffer arteries...)

so, this article and its incorporated meta-analysis do suggest that OH may well be associated with cognitive decline, and, perhaps not so surprisingly, those with symptoms on standing even if the SBP does not decrease enough to reach definitional OH (the symptoms being the body’s way of telling us that the blood pressure is too low), have an even worse prognosis. based on this study and others, i would suggest the following:

--it makes sense to check blood pressure regularly in older patients in the sitting and standing positions. this makes sense especially given that blood pressure tends to decrease progressively with aging (and i do have several patients who had hypertension, on a few meds, who end up off all meds. even 2 cases where they subsequently needed hypotension treatment with midodrine and/or fludrocortisone)

--it makes even more sense to check people in the warmer weather, where dehydration may lead to more lowering the blood pressure below the person’s usual, esp in light of the impaired baroreceptor sensitivity

--and, given the higher incidence of initial hypertension (as noted above), it makes sense to check the blood pressure several times in the 2-3 minutes after standing, beginning pretty much within the first 15 seconds of standing

--i do titrate down on the anti-hypertensives if there is OH, SOH or initial orthostatic hypotension, even if that means settling for a higher sitting BP than i would otherwise like. and, as per prior blogs, it probably makes sense to check 24-hr ambulatory BP in these patients since many may in fact have much lower blood pressures than i get in the office measurement anyway (and these 24 hour results seem to correlate much better with actual clinical cardiovascular events. See: http://gmodestmedblogs.blogspot.com/2018/04/ambulatory-blood-pressure-monitoring.html )

--i would also cut back on antihypertensives in patients or families who note cognitive decline, especially if the SBP were low in the office, and, again, consider 24-hr ambulatory monitoring.

geoff​

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