blood pressure variability increases cardiovasc disease

There has been concern about the adverse effects of blood pressure variability on cardiovascular outcomes. A prior blog (see http://gmodestmedblogs.blogspot.com/2015/07/blood-pressure-variability-and-heart.html  ) reviewed the ALLHAT trial, which found that visit-to-visit blood pressure variability was associated with increased CV events and commented on a 2010 issue of the Lancet that found that hour-to-hour BP variability in individuals was associated with more strokes, and, to a lesser degree, coronary events (see Rothwell PM. Lancet 2010;375:895). BMJ just had a systematic review and meta-analysis confirming the association (see bp variability and cvd bmj2016 in dropbox, or doi.org/10.1136/bmj.i4098). details:

-- 41 papers representing 19 observational cohort studies and 17 clinical trial cohorts. 24 papers studied long-term variability (monitoring blood pressure in clinics), 4 studies mid-term variability (home monitoring) and 15 short-term (ambulatory blood pressure monitoring).

--range of studies: 457 to 122,636 participants; follow-up ranged from 2514 to 490,544 person-years; mean age ranged from 48.5 to 77 yo

--Increased long term variability in systolic blood pressure was associated with:

    ​--all-cause mortality: 15% increase, HR 1.15 (1.09 to 1.22)

    --cardiovascular disease mortality: 18% increase, HR 1.18 (1.09 to 1.28)

    --cardiovascular disease events: 18% increase, HR 1.18 (1.07 to 1.30)

    --coronary heart disease: 10% increase, HR 1.10 (1.04 to 1.16)

    --stroke: 15% increase, HR 1.15 (1.04 to 1.27)

-- Increased mid-term variability (home BP) in daytime systolic blood pressure was associated with all-cause mortality [HR 1.15 (1.06 to 1.26)].

-- Increased short term variability (ambulatory BP) in daytime systolic blood pressure was also associated with all-cause mortality [HR 1.10 (1.04 to 1.16)]. The conclusions are a bit limited, since 2 studies dominated the meta-analysis.

commentary:

--as with meta-analyses, they combine different studies with differing methodologies, limiting their conclusions. For example, there is not necessarily any consistency across studies in terms of how the BP was measured, what size cuffs were used, whether using manual or automated devices, etc)

--they did not include studies on nocturnal dipping (that's the normal variation, with lower blood pressure at night on ambulatory monitoring; non-dippers seem to have higher mortality). They did exclude patients on dialysis, since blood pressure variability is basically intrinsic to hemodialysis patients. 

--as a perspective, the 15+% difference in cardiovascular events found still pales in comparison to overall effect of lowering the mean blood pressure. ie, the primary goal is to decrease the mean blood pressure. That being said, the difference from blood pressure variability in the above meta-analysis did control for the mean blood pressure, revealing an increased risk over the mean BP

--blood pressure variability during the day is normal, typically up to the 18/12 mmHg range. This variability is enhanced in those with arterial stiffness (and the above meta-analysis was skewed to older hypertensive patients), which may put these patients at higher CV risk.

--this all supports the conclusions that:

    --we should be doing more ambulatory or home BP monitoring: several analyses have found that ambulatory or home blood pressure monitoring is superior to office blood pressure at predicting cardiovascular events, perhaps since ambulatory or home measurements are more likely to pick up BP variability.

    --there are likely advantages to using BP meds that produce a more sustained, less variable blood pressure over 24 hours: amlodipine seems to be the best, ACE-I are intermediate (and there are arguments that the increased stroke rate in several studies of ACE-I may be related to the higher blood pressure in the early mornings), and HCTZ up to 25 mg is the worst (for example, see Webb AJS. Lancet 2010; 375: 906). b-blockers are also in the intermediate category.

--many prior blogs have assessed these last 2 conclusions, at http://gmodestmedblogs.blogspot.com/search/label/hypertension  . and in particular,

    -- http://gmodestmedblogs.blogspot.com/2016/04/chlorthalidone-is-better-than-hctz-for.html  showed that hydrochlorothiade is a poor choice, given both its very poor 24-hour effect (despite the fact that the blood pressure seems better controlled when we see the patients during the daytime in the office), and  there are several other analyses confirming this result (eg, the seminal studies on HCTZ in mild hypertension, done decades ago, involved using 50mg/d, which is higher than most of us use now. And the 50mg/d dose does decrease BP variability (see htn HCTZ Meta-anaylsis messerli am j cardiol 2011 in dropbox, or Messerli FH. JACC 2011; 57:590.)

    -- http://gmodestmedblogs.blogspot.com/2016/04/home-blood-pressure-monitoring.html which shows that home BP monitoring is superior in terms of clinical outcomes over office-based BP, and refers to the UK's 2011 NICE guidelines which documented lots of studies showing that ambulatory BP monitoring was superior to clinic BP measurement, leading NICE to strongly support using ambulatory or home BP for diagnosis of hypertension.  Though it was done in 2011, I think the NICE document is the single best review of hypertension I have seen, with a detailed analysis of the studies up til 2011 (it even reviewed 5 or so studies showing that spironolactone was great in patients with resistant hypertension, well before it was adopted in the US), but this document unfortunately is not accessible on the internet (it is in my dropbox as Htn nice recs 2011. The NICE guidelines were updated in 2015, with the summary at https://www.nice.org.uk/Guidance/QS28 ).

    -- Using a non-clinic based BP was adopted in 2015 by the USPSTF giving an "A" rating to screen BP outside of the clinical setting. for the USPSTF recommendations and my review, see http://gmodestmedblogs.blogspot.com/2015/10/uspstf-guidelines-on-blood-pressure.html