orthostatic hypotension and increased heart failure and mortality

There was an interesting subgroup analysis of the ACCORD blood pressure wing (Action to Control Cardiovascular Risk in Diabetes) which found that those with orthostatic hypotension (OH) had a significantly higher risk of mortality and heart failure events (see hypotension orthostatic ACCORD hypertension2016 in dropbox, or Fleg JL, Hypertension. 2016;68:888 ). Details:

-- the ACCORD trial had 10,251 high-risk patients with type 2 diabetes, hemoglobin A1c >7.5%, and were between 40 and 79 years old with cardiovascular disease or 55 to 79 years with anatomic evidence of subclinical atherosclerosis, albuminurea, LVH, or >= 2 additional cardiovascular risk factors. 4733 were randomly assigned to intensive vs standard blood pressure control in a non-blinded trial, with target systolic blood pressure (SBP) of <120 vs <140 mm Hg, and with no requirements as to what medications to give (clinicians' decisions)

-- 4266 participants were involved in this analysis, with blood pressure measured at baseline, and at the 12 month, and 48 month follow-up visits. The blood pressure was measured using an automated oscillometric device after the patient had been seated at least five minutes, with the blood pressure determined three times at one minute intervals. The patients then stood up and had their blood pressure measured every minute for three minutes. The patients were asked if they experienced dizziness or felt light-headed.

-- Orthostatic hypotension (OH) was defined as a decline in SBP > 20 mmHg or decline in DBP > 10 mmHg

-- the average difference in blood pressure achieved between the intensive vs standard groups was 14.2/6.1 mmHg, with the mean number of medications being 3.4 for the intensive group and 2.1 for the standard group.

-- Serious adverse events related to the intervention, including hypotension and syncope, were found in 3.3% of the intensive group compared to 1.3% of the standard group, with p<0.001

 

Results:

-- OH occurred at least once in 852 people (20.0%). In the adjusted model, this occurred most commonly in women, current smokers, those with higher baseline SBP, higher A1c, and those on beta blockers, alpha blockers or insulin. Of note, neither age nor assignment to intensive vs. standard BP treatment goals was associated with OH

-- Approximate 5% of all patients, independent of group, felt dizzy on standing. The incidence was slightly more in the intensive group but only at the 48 month examination.

-- There was no significant difference in OH prevalence, incidence, or resolution between those in the intensive vs. control groups.

-- People with OH were about twice as likely to report symptoms of dizziness on standing than those without OH, but this was only in about 17-20% of the patients who were symptomatic.

-- Those with OH had an 85% higher risk for heart failure deaths or hospitalizations (p= 0.01) and 62% higher risk for total mortality (p= 0.02).

 

Commentary:

-- In my experience, beta blockers are the medication most commonly associated with OH and large decreases in blood pressure on standing, even in those with high sitting pressures.

-- It is not so surprising that those with higher A1c's and on insulin have more OH, since they may well have more autonomic neuropathy, and there may also be some direct insulin-induced vasodilation, perhaps through endothelium-dependent mechanisms.

-- or that smokers have more OH (probably more atherosclerotic disease of their large arteries, leading to higher SBP but lower DBP because of their nondistensibility)

-- or in those who had initially higher SBP (again perhaps related to more atherosclerotic large vessel disease, leading to more isolated systolic hypertension)

-- It is, however, unexpected and striking that they found no correlation of OH with age. All of the studies I have seen have shown a significant increase with age. Perhaps part of the reason is that in this study they had an 80-year-old cut off.

-- and, there was no association with whether the patient was in the more aggressive blood pressure lowering group or not (which also supports checking orthostatics in patients with higher blood pressures)

-- so, in this study, it was unclear whether OH was simply a marker of people at higher risk of morbidity/mortality (eg more advanced diabetes, with more autonomic neuropathy, etc as above), or whether it was the cause. but given the not-so-unlikely possibility of the latter being part of the issue, I think it makes sense to assess OH regularly in patients (and i do so in all elderly hypertensive patients, even if they do not have diabetes, and have found, i think, pretty impressive 30+ mmHg drops in blood pressure even in those with systolics in the 150-160 range, and not so uncommonly...) and customize therapy to avoid excessive falls in blood pressure, whether they are symptomatic or not (the reason being: even if asymptomatic, perhaps there are times when they eat/drink less at home or outside in the heat and they become symptomatic, fall, etc; and perhaps the low flow associated with OH really is not so good for the brain, heart, kidneys, etc in the longterm.)

-- for example, there are some studies showing cognitive decline with low blood pressure: see http://gmodestmedblogs.blogspot.com/2015/04/too-low-blood-pressure-and-cognitive.html ). ​

-- another important point from the study was that dizziness is not commonly reported with clear-cut OH by blood pressure measurement (i.e. we should not rely on reported dizziness as a reliable marker of OH), and that OH is not a consistent finding each time it is measured. 

-- All of this supports my prior suggestions that we measure orthostatic blood pressures in older patients on a regular basis, even if the SBP is in the 150 range, and adjust meds accordingly (?ACCORDingly). 

(See http://gmodestmedblogs.blogspot.com/2016/05/orthostatic-hypotension-revisited.html for more studies on orthostatic hypotension, including the finding that initial hypotension on standing is in fact much more common than standard orthostatic hypotension after a couple minutes)