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Dr Manan Pareek Discusses SPRINT Trial Findings


It's interesting that we saw such a clear U-shaped mortality curve for serum bicarbonate levels in a patient population where we usually don't think about measuring bicarbonate, said Manan Pareek, MD, PhD, FAHA, FESC, an internal medicine hospital resident at the Yale University School of Medicine.

It's interesting that we saw such a clear U-shaped mortality curve for serum bicarbonate levels in a patient population where we usually don't think about measuring bicarbonate, said Manan Pareek, MD, PhD, FAHA, FESC, an internal medicine hospital resident at the Yale University School of Medicine.


The American Journal of Managed Care® (AJMC®): Baseline and on-treatment serum bicarbonate levels both displayed a U-shaped association with the risk of death. However, the association was not affected by intensive vs. standard blood pressure lowering. What do you think accounted for these findings?

Dr. Pareek: When we did this study, first of all, we wanted to test both baseline and on-treatment electrolyte concentrations because they might change with the treatment that we started in patients. The baseline concentrations were drawn before patients were uptitrated on any study regimens. So we assumed that those concentrations were bound to change a lot over the course of the study. That's why we did both of them. Our first finding, that bicarbonate was associated with mortality, that was a simple study of association. And we saw a U-shaped association, meaning that if you had low serum bicarbonate or if you had high serum carbonate, you had a high mortality compared with those individuals who had a normal serum bicarbonate. That's something that's been established from CKD patients, chronic kidney disease patients, particularly for the low bicarbonate. Patients who have metabolic acidosis are known to have a higher mortality. They have a lot of other detrimental effects on their body, their kidney disease actually progresses faster. We also know that treating with bicarbonate in these individuals may slow the progression of their CKD.

It's not something that's been studied that well in patients with hypertension. So this was a different type of cohort. And second of all, the fact that high bicarbonate also showed an association with mortality is something that's also less well established. Clinicians tend to focus on the low bicarbonate concentrations. And then the last thing that you mentioned, the fact that a treatment, whether patients were randomized to intensive or standard treatment actually didn't affect this relationship, or rather, bicarbonate didn't modify the effect of their treatment regimen. One way to interpret that would be that it's really not a matter of how intensive you're treating the blood pressure. It might have more to do with which drugs you're actually using. To be honest, from this study, it's hard for us to know whether these electrolyte changes are solely a consequence of the therapies that patients are on, or whether it's a marker of morbidity in and of itself. But I think that the fact that there's no treatment interaction points more towards something inherent in the patients rather than something that we're doing to them.

AJMC®: How can providers interpret these findings and use them to better guide patient care?

Dr. Pareek: That's a really good question. And actually, we had a sister abstract to the bicarbonate abstract that we're also presenting at this year's European Society of Cardiology (ESC) Congress on potassium concentrations. Interestingly, after full adjustment, we actually found no association between potassium concentrations and mortality in the SPRINT cohort. Our thought was that it's probably because clinicians are pretty vigilant about correcting potassium concentrations in patients with hypertension. Because anyone who initiates antihypertensive treatment in a patient knows that potassium concentrations might be affected. That's one thing. The other thing is that patients in trials are usually followed-up very strictly. So our thought was that clinicians were following them closely and they were just correcting their potassium concentrations. But there just isn't the same type of focus on bicarbonate unless you're a nephrologist, because, as I alluded to before, CKD patients are really the the patient group where the mortality effect of low bicarbonate has been established. Our thought is that maybe we should take a closer look at these bicarbonate concentrations in patients with hypertension, regardless of whether their on standard or intensive care treatment, but rather know that this is actually a marker of mortality, and perhaps think of correcting low concentrations or even high concentrations by adding sodium bicarbonate by switching around their treatment regimen. At least that's our pragmatic thought that one could do that.

AJMC®:What are the next steps in understanding the association of low bicarbonate levels with higher mortality among patients who are hospitalized or have CKD?

Dr. Pareek: That really follows the same things that we spoke about, that at this point, it's a little unclear first, whether this is a treatment effect, that thereby carbon concentrations are up or down, or whether it's something going on inherently into the patient. I think the most important next step would be to perform a study or look at observational data, perhaps even from the SPRINT cohort and see whether patients who initially had an abnormal bicarbonate concentration that then got resolved, whether that was beneficial in terms of mortality. For future trial purposes, simply treating either high or low bicarbonate versus conventional treatment and following patients and just assessing whether this has any effect on mortality.

AJMC®: Do you have any final thoughts you'd like to share?

Dr. Pareek: I think it's interesting that we were seeing such a clear U-shaped mortality curve for bicarbonate in a patient population where we usually don't think about measuring bicarbonate.

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