What's New and Useful in Hypertension From ACC.19

I have a special place in my heart for systemic arterial hypertension management. My brother had a pheochromocytoma that nearly killed him. I spent 5 days sweating on an IV magnesium drip filling one Foley bag after another when postpartum hypertension drove my blood pressure to 230/130 mm Hg.

I miss discussions on lifestyle management that modern office schedules have grown to resent. When I asked my patients with "resistant" hypertension if they ever "touch a salt shaker," I loved watching anxiety change to hope. Attending several great talks on hypertension at ACC.19 had me yearning for those office days. Here are a few salient points:

INFINITY

The INFINITY trial^[1] offered many lessons within the lesson:

Intense control of systolic blood pressure to 130 mm Hg via ambulatory monitoring did something good for the brain. It decreased white matter hyperintensity accrual by 40%. Intensive control also reduced cardiovascular events. The jury is still out on whether this helps cognition, as only marginal benefit was noted and it did nothing for mobility.

Lesson 1: Patients will actually wear an ambulatory blood pressure monitoring device.

Lesson 2: Presenter William White, MD, told me that even when cohorts are supervised, educated, and adherent, they can't accurately check their own random pressures at home.

But one additional lesson from the INFINITY trial was lost in the bright light cast by the trial design.

Cardiologists largely ignore the incidental finding of abnormal white matter intensity on brain CT and MRI, much like noncardiologists often ignore coronary calcium on CT scans. Both findings are accepted as common effects of aging instead of being seen as red flags.

We should make a pact: Cardiologists will step up our surveillance on hypertension control when we see white matter abnormalities. Noncardiologists will quantitate coronary calcium and refer for risk stratification when appropriate. There. I think we can all shake on that.

Lesson 3: Acknowledging white matter hyperintensity "as a thing" was the unspoken take-home from the INFINITY trial.

The CREOLE Trial

Sub-Saharan Africa is writhe with poorly controlled hypertension and affords a unique opportunity to study cohorts often underrepresented in major trials.

CREOLE^[2] compared three treatment groups:

Amlodipine + hydrochlorothiazide (HCTZ)
Amlodipine + perindopril
Perindopril + HCTZ

Lesson: The two amlodipine combinations demonstrated superior hypertension control.

The side effect profile was predictable:

Perindopril produced a dry cough in 5.4% of patients.
Amlodipine was associated with pedal edema in 3.9% of treated patients.
Hypokalemia developed in 5.3% of those treated with the amlodipine + HCTZ combination.

Depending on patient history and tolerance, this information provided good insight into potential treatment choices for the African population. The next step will be to look at hard outcomes.

Hypertension Treatment in the Era of Precision Medicine

Donna Arnett, PhD, from the University of Kentucky kicked off this session with a talk about the genomics of hypertension and how desperately we need dedicated gene panels to guide therapy. A question from the audience prompted her to mention how kidney biopsies, though impractical, would offer a wealth of information. Instead, we are relegated to "blood samples that supply 0.9% of the information" gleaned from tissue sampling.

In the presentation on hypertension in the older adult, we heard how important the assessment of frailty and medication reconciliation is from Eileen Handberg, PhD, APRN, from the University of Florida. She emphasized the importance of these assessments for every patient at every visit and gave examples of how the lack thereof affected specific cases.

She also said, for further emphasis, "I live in a state that is all about the functional elderly. We have 80- to 90-year-olds who start a program…. I used to not get it. I'd ask, 'Why?', but you want to slide into the pearly gates. You don't want to hobble in on a wheelchair or a walker," she explained. She added that the risk of a fall is tied to the loss of upper body strength: "We have the lifestyle conversation constantly."

Vesna Garovic, MD, PhD, from the Mayo Clinic spoke about management of complicated hypertension in pregnancy. She reminded us that methyldopa is still the obstetric favorite, and to date there is no evidence of long-term side effects on the developing fetus. "There is a balance between pregnancy termination to prevent maternal complications related to systemic disease and hypertension vs the continuation of pregnancy," she said. "We aim for a goal of 150/90 to 100 mm Hg, decreasing the diastolic for kidney disease and proteinuria," she added.

She reviewed the Control of Hypertension in Pregnancy Study data,^[3] which demonstrated that tight control of hypertension in pregnancy does not pose a risk to the fetus or the newborn while showing moderate benefits in preventing progression to severe hypertension for the mother. I came away thinking how important it is to refer these patients to clinicians who are practiced in this complicated area.

Resistant Hypertension: Resistant No More?

All of these talks were excellent, but the one on resistant hypertension by David Calhoun, MD, from the University of Alabama was extremely applicable for difficult-to-manage patients. Here are a few takeaways quotes from his talk:

Lesson 1: Renin-angiotensin-aldosterone system blockers, dihydropyridine, and the long-acting thiazide-like diuretics chlorthalidone and indapamide are the standard triple-drug regimen for resistant hypertension.

Lesson 2: He was impressed by the Pathway 2 study.^[4] "I doubt it could ever be done again in true hypertension resistance," he said. In that trial, the biggest blood pressure reductions were seen in patients treated with spironolactone, resulting in a drop of 12 mm Hg at doses of 25 to 50 mg daily. Calhoun noted that they also looked at the titration benefit of α- and β-blockers, with not much response. With titration of spironolactone from 25 mg to 50 mg, there was another 4-mm Hg reduction in systolic pressure. "There is benefit in going as high as 50 mg daily," he concluded.

Lesson 3: The patients with the largest response to spironolactone are those with suppressed renin. Calhoun told us that plasma renin activity (PRA) is the first real biochemical marker that predicts the blood pressure response and that plasma aldosterone is a weak predictor of drug response. While the strongest predictor was the aldosterone-to-renin ratio, "it was largely driven by PRA," he concluded.

Lesson 4: We should be monitoring the PRA with treatment. If the PRA remains suppressed, it's a good biomarker to guide treatment and titration.

Lesson 5: If spironolactone is not tolerated, then amiloride can be substituted.

"Four years ago I would have said there is no role for precision therapy, but that's changed," remarked Calhoun.

It's odd to enjoy so much talk about high blood pressure in the great city of New Orleans. Though I never "touched a salt shaker" in NOLA, you can bet that someone in those fabulous kitchens salted my food before my plate reached the table. My knowledge of that practice may fall under the heading of "benign neglect." I Just hope I didn't increase my white matter hyperintensity or suppress my plasma renin. But if my systolic pressure slides up a few points, I have a much better idea of what to do and who to call, thanks to the excellent lessons provided at ACC.19.

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