Low Diastolic Blood Pressure Linked to Subclinical Myocardial Damage and Coronary Events: ARIC Analysis

Very low diastolic blood pressure (DBP) is associated with an increased risk of subclinical myocardial damage, particularly among individuals with diastolic pressures less than 60 mm Hg, according to the results of a new observational study.

Importantly, the study found that low DBP was also associated with an increased likelihood of coronary heart disease events and mortality, with the highest relative risk observed for individuals with the lowest diastolic pressures. Compared with individuals with a DBP of 80-89 mm Hg, those with a DBP less than 60 mm Hg had a 50% increased risk of CHD events and a 30% increased risk of mortality.

The researchers, led by John McEvoy, MBBCh (Johns Hopkins University School of Medicine, Baltimore, MD), say their results could have a “number of potential implications” in the post-Systolic Blood Pressure Intervention Trial (SPRINT) era where the threshold for diagnosing and treating hypertension could change. “Despite the undeniable clinical benefits reported in SPRINT, one of many concerns related to aggressive [systolic blood pressure] reduction with pharmacotherapy is the possibility of myocardial ischemia by lowering DBP,” they state. “This is a concern on the basis of strong physiological rationale and a wealth of prior observational data.”

To TCTMD, Deepak Bhatt, MD (Brigham and Women’s Hospital, Boston, MA), who wrote an editorial accompanying the study, said a J-shaped relationship between low blood pressure and adverse cardiovascular events has been documented in previous studies, but one of the strengths of this latest work by McEvoy and colleagues, an analysis of the Atherosclerosis Risk in Communities (ARIC) cohort study, is that it takes things “one step further” in also showing a relationship between high-sensitivity cardiac troponin T levels (hs-cTnT) levels and DBP.

Bhatt explained that coronary blood flow typically occurs in diastole, and if DBP is reduced too much, blood flow to the heart might be impaired. In his editorial, he notes that the relationship between DBP and CHD was strongest when the baseline hs-cTnT level was ≥ 14 ng/L, “suggesting that troponin elevation may not only have been a marker of myocardial damage, but also on the causal pathway for coronary events.”  

In August, Bhatt along with the CLARIFY investigators published a similar study in the Lancet, one looking at the association between cardiovascular event rates and mortality based on the achieved systolic and diastolic pressure in patients with coronary artery disease. In that analysis, presented at the European Society of Cardiology Congress 2016 and reported by TCTMD, a DBP of less than 60 mm Hg was also associated with a two-fold increased risk of cardiovascular death, MI, or stroke when compared with individuals with a DBP between 70 and 79 mm Hg.

“If individuals have a diastolic blood pressure that is too low, there might not be enough blood flow to the heart muscle itself, and this could lead to subclinical elevations in troponin,” said Bhatt. “Perhaps then, over time, it’s not just subclinical elevations in troponin but [low DBP] is causing actual damage to the heart muscle. It’s a way of putting it all together—there’s no way of proving all that. It should be pointed out that both ARIC and CLARIFY are observational analyses. These are not randomized blood-pressure trials.”

Coronary Blood Flow Occurs During Diastole

The ARIC analysis, which is being published in the Journal of the American College of Cardiology October 18, 2016, included 11,565 adults followed for a median of 21 years.

Compared with individuals with DBP between 80 and 89 mm Hg, which served as the reference group, those with a diastolic pressure less than 60 mm Hg had a two-fold greater risk of myocardial damage as measured by elevations of hs-cTnT levels (≥ 14 ng/L). For those with DBP between 60 and 69 mm Hg, the risk of subclinical myocardial damage was 70% higher. In addition, the researchers report that low DBP at baseline was independently associated with “progressive myocardial damage” based on changes in hs-cTnT levels that occurred over a 6-year period (between visits 2 and 4). Compared with the reference group, those with DBP less than 60 mm Hg had an estimated 1.5-ng/L larger annual change in hs-cTnT levels.

Regarding clinical events, individuals with a baseline DBP 60-69 mm Hg and 70-79 mm Hg had a 23% and 20% increased risk of CHD, respectively, when compared with those with a baseline DBP between 80 and 89 mm Hg. The association was strongest for fatal CHD and MI. There was no association between DBP and stroke after adjusting for systolic blood pressure and clinical confounders.

To TCTMD, Bhatt said a valid criticism of the ARIC analysis, as well as CLARIFY, is that individuals with low DBP are sicker individuals and worse outcomes would be expected. Although undetected confounding variables in observational analyses are a possibility, Bhatt said, the stroke findings suggest the findings are real. In CLARIFY, like ARIC, low DBP was associated with a higher risk of MI but not stroke.

“Therefore, if you thought that these were simply sick people, and that this has nothing to do with the low blood pressure per se, then you’d not only have a lower risk of heart attack but also a higher risk of stroke,” said Bhatt. “They’d have a higher rate of all these adverse events.” The observational studies, broadly speaking, suggest that a low DBP is harmful in terms of increasing the risk for MI. “Lower isn’t necessarily better in terms of blood pressure reduction,” he said.

The latest registry analyses, he added, suggest that physicians should exercise caution before getting “too aggressive” in reducing blood pressures in patients, particularly to very low DBP.

SPRINT Races Into the Mix

In SPRINT, which was presented and published nearly 1 year ago, researchers showed that treating to a target of less than 120 mm Hg versus the standard target of less than 140 mm Hg reduced the rate of adverse clinical outcomes in patients at high risk for cardiovascular events.

Reconciling the J-shaped curves observed in the ARIC and CLARIFY analyses with SPRINT, Bhatt noted that the blood-pressure measurements in SPRINT have been debated amongst hypertension experts, particularly since the technique differed so much from previous trials. As noted previously, SPRINT used a programmed automated oscillometric blood-pressure meter that required approximately 8 minutes of quiet rest, with measurements designed to be taken when medical personnel were outside the room. Unattended blood-pressure measurements can be significantly lower than a typical office measurement, with some arguing that SPRINT patients likely achieved an office blood pressure of 130 or 135 mm Hg.

“The results of SPRINT—although I believe them and think they’re real—the cutoffs of 120 and 140 [mm Hg] probably need to be adjusted upward,” said Bhatt. “The datasets might not be as discordant as they seem from a distance.”

Despite the ongoing debate over SPRINT, and whether or not the hypertension guidelines will be adjusted to reflect the new targets, Bhatt said many patients have the opposite problem in that their blood pressure is still far too high. Rather than focusing on whether or not there is a J-curve at 60 or 70 mm Hg, the focus should be on treating individuals with uncontrolled hypertension. For the physician looking to lower risk further in patients currently treated, Bhatt said attention to DBP should be paid to patients of advanced age and those with obstructive coronary disease, heart failure, and renal dysfunction, among other factors.    

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