Drugs, diet and delivery can optimize hypertension outcomes
Findings evaluate dietary sodium reduction, postpartum blood pressure, an investigational RNA interference therapeutic agent and BP control and dementia risk.
Investigators in four trials revealed findings during Saturday’s Late-Breaking Science Session, Using Drugs, Diet and Delivery to Optimize Hypertension Outcomes. Results from these trials found:
- Reducing dietary sodium lowers systolic blood pressure for patients with and without hypertension.
- Improved postpartum blood pressure control has long-term blood pressure and cardiac benefits.
- Zilebesiran, an investigational RNA interference therapeutic agent, reduced blood pressure >15 mmHg.
- Blood pressure control could be linked to decreased dementia risk.
Food for thought: More patients to likely benefit from reducing dietary sodium
Dietary sodium intake can have a significant effect on blood pressure among people with and without hypertension (HTN), including those who are already on medications to lower blood pressure, researchers said.
Estimates from older studies suggest about 50% of people with HTN and 25% of people with normal blood pressure are salt sensitive. Are those numbers still accurate? That’s among the questions asked in Effects of Dietary Sodium on Systolic Blood Pressure in Middle-Aged Individuals: A Randomized Order Cross-Over Trial (CARDIA-SSBP), a cohort of the Coronary Artery Risk Development in Young Adults (CARDIA) study that also included non-CARDIA participants from Birmingham, Alabama, and Chicago.
The randomized, crossover trial enrolled 213 people across the spectrum of blood pressure control, including people with normal blood pressure, controlled HTN, uncontrolled HTN and untreated HTN.
During the three-week trial, participants attended a baseline visit on their usual diet and were then randomized to a high sodium diet (2,200 mg sodium added to the usual diet) or a prepared, standardized low-sodium (500 mg daily total) diet for one week before crossing over to the opposite diet.
Blood pressure outcomes were recorded using 24-hour ambulatory monitoring devices on the last day of each of the three weeks. Since most of the sodium we consume is excreted in urine, participants in the trial also collected urine for 24 hours on the final day of each week to assess the amount of sodium in their diet.
“On the low-sodium diet, participants achieved a median consumption of about 1,300 mg of sodium, which is a reduction of about 2,300 mg or one teaspoon of sodium from their usual diet,” said Norrina Allen, PhD, the study’s co-principal investigator and professor of epidemiology at Northwestern University. Compared with the usual diet, the high-sodium diet did not raise systolic blood pressure (p=0.14).
Deepak K. Gupta, MD, MSCI
“The baseline amount of sodium averaged around 4,500 milligrams of daily sodium, which suggests that the usual diet for most adults is already saturated with sodium and adding to it does not substantially increase blood pressure,” said Deepak K. Gupta, MD, MSCI, the study’s co-principal investigator and director of the Vanderbilt Translational and Clinical Cardiovascular Research Center.
However, the low-sodium diet induced a decline in systolic blood pressure in 72% of study participants compared with their blood pressure on the usual diet. The median within-individual change in systolic blood pressure between the high- and low-sodium diet was 7 mmHg (p<0.001). This decline in systolic blood pressure with the low-sodium diet was independent of HTN status and anti-hypertensive medication use, consistent across subgroups, and did not result in excess adverse events.
Participants taking medications to control their blood pressure had a similar reduction in blood pressure with the low-sodium diet as participants with HTN who were not on anti-hypertensive medications, emphasizing the importance of dietary sodium reduction in addition to medications to lower blood pressure.
“The decreases in blood pressure we observed could have a major impact on an individual’s future risk of heart disease and death; prior studies have shown that every 5 mm Hg lower blood pressure significantly reduced the risk for all-cause mortality by up to 8%,” Dr. Allen said.
CARDIA-SSBP suggests the majority of middle-aged adults can get a blood pressure benefit from reducing dietary sodium, even patients taking anti-hypertensive medication — and that salt sensitivity is more prevalent than previously estimated.
“In our study, three out of four people benefited from lowering their dietary sodium intake,” Dr. Gupta said. The study was published online in JAMA Network Open following the presentation.
Blood pressure control during postpartum has long-term CV impact
Affecting roughly 10% of women, pregnancy hypertension is common and results in adverse cardiac remodeling and an increased incidence of hypertension and future cardiovascular diseases.
Still, how blood pressure is managed in the weeks after pregnancy, as a patient’s cardiovascular system recovers from the hypertensive episode, may be critically important for determining future cardiovascular health, according to the Long-Term Blood Pressure Control After Physician Optimized Postpartum Blood Pressure Self-Management: The POP-HT Randomized Clinical Trial.
The prospective, open-label, blinded endpoint trial enrolled 220 participants 18 years and older in the U.K. with pre-eclampsia or gestational hypertension who required antihypertensive medication on hospital discharge postnatally. They were randomized 1:1 to self-monitoring with a wireless blood pressure monitor and physician-optimized antihypertensive titration or usual postnatal care, which included a primary care doctor or midwife checkup five to 10 days after hospital discharge, and again six to eight weeks later.
The primary endpoint, 24-hour mean diastolic blood pressure, measured at around nine months postpartum, was 5.8 mmHg lower in those who received the intervention compared with the usual care (P<0.001). Similarly, 24-hour systolic blood pressure was 6.5 mmHg lower in the intervention group (p<0.001). 
Jamie Kitt, DPhil
“Optimizing blood pressure with self-monitoring and physician-guided titration of antihypertensive medication for the first few weeks after pregnancy resulted in a persistent reduction in blood pressure for at least nine months,” said Jamie Kitt, DPhil, British Heart Foundation Fellow at the University of Oxford in the United Kingdom.
“This long-term reduction in blood pressure was seen even though most study participants stopped blood pressure medication after a few weeks.”
Dr. Kitt said women with pregnancy hypertension are at a significantly greater risk of cardiac problems in later life; one third will develop hypertension again within 10 years of pregnancy and their risk of early heart attack and stroke doubles.
“Although we can advise women who have just had pregnancy hypertension of their future risk, many don’t receive follow-up care after hospital discharge,” said Paul Leeson, MD, professor of cardiovascular medicine at the University of Oxford and the study’s principal investigator.
“This trial suggests, however, that focusing health care on improving blood pressure control for just a few weeks after pregnancy can significantly reduce the chances of needing to return to the hospital with blood pressure problems during the immediate postpartum period. Intervention may also reset postpartum blood pressure at a lower level, which could have long-term benefits for women’s cardiovascular health.”
Following the presentation, the study’s primary results will be published in the Journal of the American Medical Association.
Zilebesiran safely reduced systolic blood pressure
Zilebesiran, an investigational RNA interference therapeutic agent that blocks hepatic angiotensinogen expression, leading to decreased production of angiotensinogen protein and suppressed synthesis of angiotensin I and angiotensin II, demonstrated a clinically significant reduction in blood pressure.
That gives it the potential to become a foundational therapy, according to Sustained Blood Pressure Reduction With the RNA Interference Therapeutic Zilebesiran: Primary Results From KARDIA-1.
The phase 2 KARDIA-1 study enrolled 394 patients with untreated hypertension or were on stable therapy. After antihypertensive washout, patients were randomized to one of five treatment arms during a 12-month double-blind period and double-blind extension period: 150 mg or 300 mg subcutaneous Zilebesiran once every six months; 300 mg subcutaneous Zilebesiran once every three months; 600 mg subcutaneous Zilebesiran once every six months; or placebo subcutaneously once every three months for the first six months.
After three months of treatment, Zilebesiran achieved a placebo-subtracted reduction >15 mmHg with both 300 mg and 600 doses (p<0.0001) in 24-hour mean systolic blood pressure measured by ambulatory blood pressure monitoring, meeting its primary endpoint, with sustained blood pressure reductions at month six for all doses.
Zilebesiran also demonstrated a favorable safety profile over six months. No drug-related adverse events were classified as serious or severe. 
George Bakris, MD
“Up to 80% of patients with hypertension remain uncontrolled, which carries a substantial risk of morbidity and mortality, resulting in lowered quality of life and substantial significant health care and societal costs,” said George Bakris, MD, director of the AHA Comprehensive Hypertension Center at the University of Chicago Medicine and the study’s principal investigator.
“These KARDIA-1 results give confidence in the potential for Zilebesiran to address the significant unmet needs of these patients who are at high risk of future cardiovascular events.”
Zilebesiran will be further evaluated in two additional phase 2 studies, KARDIA-2 and KARDIA-3, and a phase 3 cardiovascular outcomes trial.
Blood pressure reduction linked to decreased dementia risk
Lowering blood pressure can effectively reduce the risk of dementia in patients with hypertension, according to Effectiveness of Blood Pressure-Lowering Intervention on Risk of Total Dementia Among Patients With Hypertension: A Cluster-Randomized Effectiveness Trial (CRHCP).
Dementia is a leading cause of death and disability worldwide, according to the World Health Organization. It is estimated that the global number of individuals living with dementia would increase from 57.4 million in 2019 to 152.8 million in 2050. No proven interventions prevent or delay the development — until now.
The 48-month study randomized 33,995 people ≥age 40 in 326 rural villages in China with untreated blood pressure ≥140/90 mmHg or with blood pressure ≥130/80 mmHg taking antihypertensive therapy or at high risk for CVD, which included history of myocardial infarction, stroke or heart failure.
Of the villages, 163 were randomized to usual care and 163 to an intervention in which trained nonphysician community health care professionals with supervision from primary care physicians and hypertension specialists initiated and titrated antihypertensive medications according to a simple stepwise protocol to achieve a systolic and diastolic blood pressure control of <130/80 mmHg. 
Jiang He, MD, PhD, FAHA
At 48 months, mean systolic and diastolic blood pressure was 127.6/72.6 mmHg, respectively, in the intervention group and 147.7/81.0 mmHg in the usual care group. The primary outcome for this study, dementia adjudicated independently by two neurologists blinded to intervention assignments according to standard protocol, was significantly lower in the intervention group compared to the usual-care group, 1.12% versus 1.31% per year, (p=0.0035).
“This was the first study to show hypertension control can significantly reduce the risk of dementia,” said Jiang He, MD, PhD, FAHA, director of Tulane University Translational Science Institute and the study’s principal investigator. “This proven-effective intervention should be widely scaled up to reduce the global burden of dementia.”
Further research is needed among the U.S. population, Dr. He said.
