at Cedars-Sinai and colleagues report that women with Type 2 diabetes diagnosed with hypertension before age 50 may benefit from intensive blood pressure treatment.

The findings, published in Diabetes Care, show the risk of developing cardiovascular disease is reduced in women with Type 2 diabetes diagnosed with hypertension in middle age who underwent intensive blood pressure treatment. This risk was not reduced in women diagnosed with hypertension at age 50 or older, or in men.  

“We have known for some time that women with Type 2 diabetes have greater cardiovascular disease risks than men with Type 2 diabetes,” said Susan Cheng, MD, MPH, the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science in the Department of Cardiology in the Smidt Heart Institute, and co-corresponding author of the study.

“We also know blood pressure in women rises faster than in men. Given these two findings, we wanted to find out whether certain women might benefit from more intensive treatments,” added Cheng, who is also director of the Institute for Research on Healthy Aging in the Smidt Heart Institute.

Blood pressure readings measure the force of blood pushing against the walls of the arteries. The readings measure two numbers: The larger number (systolic) is the pressure when your heart beats, and the smaller number (diastolic) represents the pressure between beats.

Experts define intensive blood pressure treatment as aiming to achieve and maintain a blood pressure below 120 mmHg systolic. Standard blood pressure treatment aims to achieve and maintain a reading less than 140 mmHg systolic. Uncontrolled blood pressure can damage the arteries and cause heart attack, stroke and other cardiovascular issues.

Intensive blood pressure treatment typically involves higher doses of antihypertensive drugs but can also involve increasing the number of antihypertensive drugs a patient is taking to achieve the blood pressure target.

The investigators analyzed data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which randomized 4,733 people with Type 2 diabetes to intensive or standard antihypertensive treatment targets. A total of 3,792 participants provided their age at hypertension diagnosis.

Women with Type 2 diabetes and early-onset hypertension who received intensive compared to standard antihypertensive treatment had significantly fewer strokes, heart attacks, and other cardiovascular events over the course of 4 ½ years than women with Type 2 diabetes and hypertension diagnosed at a later age.  

“This study could help clinicians consider situations where more intensive lowering of blood pressure may be beneficial,” said Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology. “Research findings such as these remind us that we have to consider individual differences, including differences between women and men and between people who developed their conditions earlier or later in life.”

Prospective studies are needed to validate these findings, according to the authors.

“This may be the first study to suggest intensive antihypertensive treatment is a preferred approach for women with Type 2 diabetes and early-onset hypertension,” said Joseph Ebinger, MD, associate professor of Cardiology in the Department of Cardiology in the Smidt Heart Institute and one of the study’s authors. “Our results are in line with the well-known adage that treating hypertension soon after diagnosis prevents many health issues later in life.”

Alan Kwan, MD, assistant professor in the Department of Cardiology at Cedars-Sinai, also worked on the study. Other authors include Hongwei Ji, MD; Karen Reue, PhD; Jennifer C. Sullivan, PhD; and John Shyy, PhD.

This work was funded in part by part by the National Natural Science Foundation of China (82103908), the Natural Science Foundation of Shandong Province (ZR2021QH014), Shuimu Scholar Program of Tsinghua University, National Postdoctoral Innovative Talent Support Program (BX20230189), and National Institutes of Health (grants U54-AG065141, U54-HL170326, and U54-HL169191).

Read more from the Cedars-Sinai Blog: Cedars-Sinai Investigators Exploring the Connection Between the Microbiome and Diabetes

blood pressure in patients with difficult-to-treat hypertension.

Cedars-Sinai is part of a clinical trial testing the safety and efficacy of the device, which is now commercially available after the U.S. Food and Drug Administration approved it in late 2023.

“This is another tool in our arsenal for patients who have not otherwise been able to control high blood pressure with medication or lifestyle changes,” said Florian Rader, MD, MSc, medical director of the Hypertension Center of Excellence in the Smidt Heart Institute, and the principal investigator of the Cedars-Sinai trial.

For some patients, undergoing this procedure could mean having to take fewer daily medications.

“Patients with treatment-resistant high blood pressure often take upward of four medications to manage their condition,” Rader said. “These patients often can’t control their blood pressure—placing them at significantly higher risk of heart attack, stroke and kidney failure.”     

The device delivers ultrasound energy through the arteries of the kidneys to deaden surrounding nerves that are overactive in many people with hypertension. Research shows that reducing the activity of these nerves can help lower blood pressure.

To deliver the ultrasound energy where it needs to go, an interventional cardiologist threads a narrow, flexible tube called a catheter through an intravenous line from the groin into the aorta and into one of the renal arteries. At the tip of the catheter is an ultrasound transducer that is covered by a water-filled balloon to cool and help protect the lining of the renal artery. The catheter is connected to a generator that powers and controls the ultrasound catheter.

Once the catheter is in place, the cardiologist uses a remote control to send the ultrasound energy through the wall of the renal artery to the surrounding nerves. Each delivery of ultrasound energy lasts a few seconds and is typically done about two to three times in different positions in the same artery. The cardiologist then guides the catheter to the renal artery going into the other kidney and repeats the process. When complete, the cardiologist removes the catheter and intravenous line.

The entire procedure takes about an hour.

“This is a novel way to target a neurobiological process involved in hypertension for which medications are not always effective,” said Suhail Dohad, MD, an interventional cardiologist with the Smidt Heart Institute who has performed the procedure.

Experts at the Smidt Heart Institute focus on personalizing care.

“Patients who come to the Smidt Heart Institute have options, and that is the direct result of our passion for studying new treatments for cardiovascular diseases,” said Christine Albert, MD, MPH, chair of the Department of Cardiology and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology.

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Read more on the Cedars-Sinai Blog: High Blood Pressure: How to Recognize and Treat It

With this certification, the Smidt Heart Institute becomes the association’s only Comprehensive Hypertension Center in Los Angeles and one of only three in California.

Research shows that patients have better outcomes when they are treated at an accredited center by physicians specialized in the disease.

“We offer a multidisciplinary and multispecialty approach for a comprehensive evaluation and optimal management of hypertension,” said Florian Rader, MD, MSc, medical director of the Hypertension Center, co-director of the Clinic for Hypertrophic Cardiomyopathy and associate director of the Noninvasive Laboratory in the Smidt Heart Institute. “Our treatment protocols include recommendations for lifestyle modifications that can help lower blood pressure, a comprehensive assessment of in-office and out-of-office blood pressure, including 48-hour automated ambulatory blood pressure monitoring, and medications that are both tolerable and convenient to take.”

Hypertension Center physicians also are among the most experienced in specialized care for people with secondary hypertension caused by primary aldosteronism (a disorder of the adrenal glands), pheochromocytoma (an often-benign tumor of the adrenal gland) or renal artery stenosis (blockage of the kidney artery often caused by cholesterol plaque buildup).

Evaluation, testing and treatments for secondary hypertension include hormone testing and analysis, imaging of the adrenal glands and renal arteries, and surgical procedures led by specialty-trained surgeons.  

In addition to providing evidence-based treatments, the center also gives patients access to clinical trials studying new pharmacologic and device-based treatment options.

“We are continuously aiming to make further advancements in how we diagnose and treat hypertension, including the most complex cases—which was among the criteria used in evaluating our Hypertension Center’s application for accreditation,” said Natalie Bello, MD, MPH, director of Hypertension Research in the Smidt Heart Institute. “We’re always eager to explore new, more effective options for our patients.”

The American Heart Association regularly updates its accreditation criteria to reflect the latest evidence and guidelines in hypertension care. The process involves thoroughly evaluating a healthcare institution's practices and protocols. A team of experts, including physicians, researchers, and other healthcare professionals, reviews patient care, staff training, clinical research, community outreach and quality improvement initiatives.

The Smidt Heart Institute is ranked #1 in California and #3 in the nation for Cardiology and Heart Surgery by U.S. News and World Report’s “Best Hospitals 2022-23.”

Read more on the Cedars-Sinai Blog: High Blood Pressure | What Women Need to Know

Novel research from investigators in the Smidt Heart Institute at Cedars-Sinai, published today in the peer-reviewed journal Hypertension, found that aRH prevalence was lower in a real-world sample than previously reported, but still relatively frequent—affecting nearly 1 in 10 hypertensive patients.

Through their analysis, investigators also learned that patients with well-managed aRH were more likely to be treated with a commonplace medication called mineralocorticoid receptor antagonist, or MRA. These MRA treatments were used in 34% of patients with controlled aRH, but only 11% of patients with uncontrolled aRH.

“Apparent resistant hypertension is more common than many would anticipate,” said Joseph Ebinger, MD, assistant professor of Cardiology in the Smidt Heart Institute and corresponding author of the study. “We also learned that within this high-risk population, there are large differences in how providers treat high blood pressure, exemplifying a need to standardize care.”

Study findings were based on a unique design, which used clinically generated data from the electronic health records of three large, geographically diverse healthcare organizations. Of the 2,420,468 patients analyzed in the study, 55% were hypertensive. Of these hypertension patients, 8.5%, or 113,992 individuals, met criteria for aRH.

According to Ebinger, treating aRH can be just as tricky as diagnosing it.

In fact, the “apparent” in apparent resistant hypertension stems from the fact that before diagnosis, medical professionals must first rule out other potential reasons for a patient’s blood pressure to be high.

These reasons might include medication non-adherence, inappropriate medication selection, or artificially elevated blood pressure in the doctor’s office—known as “white coat hypertension.”

“Large amounts of data tell us that patients with aRH, compared to those with non-resistant forms of hypertension, are at greatest risk for adverse cardiovascular events,” said Ebinger, director of Clinical Analytics in the Smidt Heart Institute. “Identifying these patients and possible causes for their elevated blood pressure is increasingly important.”

The takeaway, Ebinger says, is awareness—for both medical professionals and patients. He says providers should be mindful that if it’s taking four or more antihypertensive medications to control a patient’s blood pressure, they should consider evaluation for alternative causes of hypertension, or refer patients to a specialist.

Similarly, patients should lean on their medical providers to help them navigate the complex disease, including having a conversation around strategies for remembering to take their medication and addressing possible treatment side effects.

Treating patients with complex cardiac issues like aRH is at the heart of Cedars-Sinai’s expertise.

The Smidt Heart Institute was recently awarded the American Heart Association’s Comprehensive Hypertension Center Certification, recognizing the institute’s commitment to following proven, research-based treatment guidelines to care for people with complex or difficult-to-treat hypertension.

“This accreditation, coupled with our clinical and research expertise in hypertensive diseases, serves as a mark of excellence,” said Christine M. Albert, MD, MPH, chair of the Department of Cardiology and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology. “These efforts signal to patients, healthcare providers, and the community that the Smidt Heart Institute is committed to delivering evidence-based, comprehensive care for hypertension.”

Funding: This work was supported in part by Cedars-Sinai Medical Center and by the National Institutes of Health grant K23-HL153888.

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Read more from the Cedars-Sinai Blog: High Blood Pressure: What Women Need to Know