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High blood pressure is a risk factor for stroke, heart failure, and other cardiovascular diseases. Lowering blood pressure by only 10 mmHg can significantly reduce the risk of these events. However, resistant hypertension poses even higher risks of cardiovascular complications, including stroke and heart failure, compared to other forms of hypertension. Further increasing risk, patients with resistant hypertension often have other comorbidities like obesity, diabetes, and kidney disease.

, Swapnil Hiremath, MD, MPH, discusses his 

National Kidney Foundation (NKF) 2024 Spring Clinical Meeting

 presentation regarding the epidemiology, diagnosis, and pathophysiology of resistant hypertension. Hiremath is a staff nephrologist at the Ottawa Hospital, an associate professor in the Faculty of Medicine at the University of Ottawa, and an associate scientist in the Clinical Epidemiology Program at the Ottawa Hospital Research Institute.

 How does resistant hypertension differ from other types of hypertension?

 As blood pressure goes up, the risk of subsequent stroke and heart failure almost linearly goes up. It also increases the risk of heart disease, like coronary artery disease, and is associated with a high risk of kidney disease.

If we look at the large meta-analyses, it clearly shows that reducing blood pressure by roughly 10 mmHg will reduce the risk of heart failure and stroke by about 30%, reduce the risk of coronary artery disease by anywhere from 15 to 20%, reduce all-cause mortality by about 10%, and reduce kidney failure by about 5%. If you look at resistant hypertension, though, these patients have an even higher risk—2 to 3 times higher.

Another factor to consider is if it this has to do with resistant hypertension or if has something to do with the patient themselves. For example, in as I alluded to earlier, people who have resistant hypertension tend to be older, and are more likely to be obese, have diabetes, and have kidney disease. Therefore, some providers argue that it's not the resistant hypertension, per se, but it's all these other things combined.

Additionally, we look at the pill burden in a patient with resistant hypertension. They’re sometimes taking medications for blood pressure, diabetes, kidney medications, and heart medications. And this makes it challenging from a quality-of-life perspective as well.

What evidence-based approaches or guidelines are commonly used in the management of resistant hypertension?

There are many aspects at play here. But even in the diagnosis, we examine adherence. If they patient is not taking the medication, then their blood pressure will not be controlled.

The issue is that hypertension is asymptomatic. If my back is hurting, I feel it. If I have a headache, I feel it. If I have angina, I feel it. So, if I am prescribed I a painkiller, I'm more likely to take it because it is giving me relief. Conversely, if you give a patient a blood pressure pill, they will take it and they don't feel any difference, they are more likely to stop taking it.

Either they don't feel any different or they have side effects. For example, amlodipine can cause swelling of the legs, an angiotensin-converting enzyme (ACE) inhibitor can cause cough, and beta blockers can increase fatigue. Therefore, they take the pills because they don't feel good.

We have performed a recent systematic review where we evaluated the rates of non-adherence in the resistant hypertension. Results showed the rates of non-adherence in resistant hypertension is anywhere from 15 to 45%.

One way to determine adherence is to ask the patient if they are taking their pills. Alternatively, you can check if they are filling prescriptions, but that’s kind of an indirect assessment. But providers can also do a direct assessment by checking the patient's blood or urine to see if they have the blood pressure pill in their system. That's the more precise way. With direct methods, the non-adherence rates are closer to 45%. I would argue that this is a more accurate way of measuring non-adherence.

How do you fix adherence? You sit down and talk to the patient and ask—in a non-judgmental way—why aren’t you taking your pills? Are they having any side effects? Is it a question of finances and coverage? It requires bedside manner and time—it's nothing fancy. I talk about this because this is the area where we have done some studies, with direct observed therapy and with our systematic review.

Once you do that, you have to figure out if they have a secondary cause of hypertension. Sometimes, as people age, they have high blood pressure due to genetic or familial reasons. One of the most common reasons is something called primary aldosteronism. Another one is when there is renal artery stenosis, which is the narrowing of the kidney arteries. There are also some drugs that can cause hypertension. Once we understand the reason, we can treat accordingly.

If it's primary aldosteronism, we use a drug called eplerenone and we dose it higher to get the blood pressure under control. In terms of what evidence we have, there is a trial that took patients who were treated with 3 drugs and they added either an alpha blocker (doxazosin), a beta blocker (bisoprolol), or an aldosterone antagonist (spironolactone). Results showed that spironolactone was most effective of the 3 verse Is placebo at reducing blood pressure.

A new player in this system is something called aprocitentan, which was approved in the US in March of 2024.

The other intervention is called renal denervation, which involves placing a catheter in the kidney arteries. There are 2 devices now available to lower hypertension.

Lastly, lifestyle changes are also useful. This includes reducing salt, increasing exercise, and weight loss.

Articles

Swapnil Hiremath, MD, MPH, discusses resistant hypertension, including using an evidence-based approach to management and addressing non-adherence. 

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Addressing Non-Adherence in Resistant Hypertension, with Swapnil Hiremath, MD, MPH

Focusing in on Novel Oral Systemic Therapies for Moderate Plaque Psoriasis: Medcast Video

Videos

Lauren Miller, MPAS, PA-C, leads an expert discussion surrounding exciting developments in the treatment landscape of plaque psoriasis.

Medcast Videos

Tim Smith joined the MJH Life Sciences team as an assistant editor for HCPLive in August 2022. He graduated from UC Berkeley with a degree in political science, working in multimedia journalism as a staff writer prior to joining MJH. In his spare time, he enjoys reading, watching TV, listening to podcasts, and rock climbing. You can contact him at 

 risk loci were identified in recent findings, with this genome-wide analysis providing genetic evidence for a close association between psoriasis and socio-economic status, mood symptoms, obesity, and education level.

This analysis, led by Anni Heikkilä of the University of Oulu’s research unit of population health in Finland, was carried out by the investigators to identify additional risk loci for developing psoriasis. Heikkilä et al. noted that heritability of psoriasis has been estimated to be around 70% and known risk loci have been previously reported interleukin (IL)-23/IL-27-signaling pathway-related genes as well as others.

“To do this, we analyzed genome-wide data of over 900000 people from Finland (FinnGen), Estonia (The Estonian Biobank), and United Kingdom (UK Biobank),” Heikkilä and colleagues wrote. “We further utilized the newly generated genome-wide results to evaluate genetic correlations and causal inferences between psoriasis and other traits.”

The investigators noted the human leukocyte antigen (HLA) region and especially HLA-C, are known risk loci for psoriasis. Another association with psoriasis is that of kappa-light-chain-enhancers of activated B-cells (NF-κB)- as well as genes related to interleukin (IL)-23/IL-27-signaling pathways.

The research team also cited the known epidemiological risk factors which impact psoriasis risk, highlighting smoking, stress, and obesity, as well as some others. Many different comorbidities have also been known to be linked with psoriasis, including other inflammatory conditions, cardiovascular diseases, and psychiatric issues.

The team set out to enhance the overall understanding of genetic risk factors, carrying out a genome-wide association study (GWAS) on the genome-wide information of more than 900000 individuals included in the UK Biobank, FinnGen, and the Estonian Biobank. Specifically, the initial GWAS used FinnGenn and was later followed by a replication study and meta-analysis using the data from both the Estonian Biobank and UK Biobank.

The investigators' combined analyses involved a total of 925,649 subjects, with 22,659 psoriasis cases and 902,990 controls specifically. This made the study’s sample size the most extensive, in terms of psoriasis research, to date.

The research teams’ subsequent analyses were done to more closely assess the genetic correlations and potential causal relationships between psoriasis and various traits, looking at 99 phenotypes and these traits and their associations.

Six previously-unidentified loci associated with risk of developing psoriasis were reported on by the investigators. One key aspect of pathogenesis of psoriasis is the excessive proliferation of keratinocytes, the primary cells in the epidermis.

A likely candidate gene which the research team identified was the FGFR4 gene at 5q35.3, noted in a FinnGen-specific locus, and this is due to its role as a fibroblast growth factor receptor which is also known to promote keratinocyte proliferation. This contributes substantially to the characteristic hyperproliferation in skin affected by psoriasis.

Another notable feature of psoriatic skin is increased angiogenesis, or the formation of new blood vessels. This is also linked to the proliferation of keratinocytes among those with psoriasis. The remaining candidate genes reported by the investigators were noted as appearing to be involved with patients’ immune systems, with various roles potentially involved in the disease process.

Genetic correlations were found by the research team between 319 different phenotypes and psoriasis, some of which included traits related to body measurements, physical activity, other forms of disease, smoking, mood, pain, medication use, education level, and blood metabolites.

A few of the major traits highlighted, such as smoking, higher disease prevalence, high body mass index (BMI), lower attainment of education, and having children at a younger age, were described by the team as linked with lower socioeconomic status. Therefore, lower socioeconomic status was linked to exacerbations of psoriasis symptoms.

“With Mendelian randomization we found evidence of causal relationships between obesity and psoriasis, psoriasis and mood symptoms, and complex causal relationships between psoriasis and low education level,” they wrote. “Our findings deepen understanding of psoriasis and may be useful in treatment development.”

Heikkilä A, Sliz E, Kettunen J, et al. GENETIC STUDY OF PSORIASIS HIGHLIGHTS ITS CLOSE LINK WITH SOCIO-ECONOMIC STATUS AND AFFECTIVE SYMPTOMS. J Invest Dermatol. 2024 May 17:S0022-202X(24)00358-0. doi: 10.1016/j.jid.2024.03.043. Epub ahead of print. PMID: 38763176.

Lønnberg AS, Skov L, Thomsen SF, et al. Heritability of psoriasis in a large twin sample. British Journal of Dermatology. 2013; 169 (Available from:): 412-416. https://onlinelibrary.wiley.com/doi/10.1111/bjd.12375.

Nair RP, Duffin KC, Goldgar D, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways. Nat Genet. 2009; 41 (Available from): 199-204 http://www.nature.com/articles/ng.311.

These data on genetic correlations allow for new genetic evidence connecting psoriasis and patients’ socioeconomic status.

Plaque Psoriasis

The HCPLive plaque psoriasis page is a resource for medical news and expert insights on psoriasis. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for psoriatic disease, and more.

Genetic Study Identifies Several Key Risk Factors Linked to Developing Psoriasis

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New data from the phase 3 STARS trial evaluating the safety and efficacy of once-weekly subcutaneous apraglutide in patients with short bowel syndrome with intestinal failure (SBS-IF) were presented in a late-breaking session at 

Results showed significantly more patients treated with the long-acting synthetic GLP-2 analog gained additional days off from parenteral support per week and were clinical responders or clinical high responders, building upon previous positive topline data announced earlier in 2024.

“In terms of quality of life, it’s very complicated,” Francisca Joly, MD, PhD, professor of nutrition and gastroenterologist at Beaujon Hospital, explained to HCPLive as she described the burden of parenteral support in patients with SBS-IF. “The patient feels that they’ve lost freedom due to the impact of parenteral support.”

Joly explains the burden of parenteral support and the significance of new STARS data showcasing apraglutide’s potential in SBS-IF.

Francisca Joly, MD, PhD: Apraglutide in Short Bowel Syndrome with Intestinal Failure

A multicenter, double-blind, randomized, placebo-controlled trial, STARS was conducted in 18 countries with enrollment from 68 study sites and is the largest global SBS-IF clinical trial to date, including a total of 164 patients who were randomly assigned in a 2:1 ratio to receive once weekly apraglutide or placebo. The primary endpoint was relative change from baseline in actual weekly parenteral support volume at week 24, along with multiple secondary endpoints assessing the reduction in days on parenteral support and volume of parenteral support from baseline as well as enteral autonomy.

Data presented at DDW showed significantly more apraglutide patients gained additional days off from parenteral support per week at week 24 versus placebo (≥2 days, 24.5% vs 11.3%; P = .021 and ≥3 days, 11.8% vs 1.9%; P = .006), and significantly more patients treated with apraglutide were clinical responders and clinical high responders, defined as ≥20% and ≥40% parenteral support volume reduction, respectively, at both weeks 20 and 24 versus placebo. Investigators pointed out this was consistent across both the overall (Clinical responders, 42.7% vs 20.8%; P = .003; Clinical high responders, 22.7% vs 9.4%; P = .018) and the stoma populations (Clinical responders, 40.7% vs 15.4%; P = .02; Clinical high responders, 20.4% vs 0%; P = .009).

Additionally, enteral autonomy was achieved by 7 apraglutide-treated patients by week 24, including 3 in the stoma subpopulation and 4 in the colon-in-continuity subpopulation (6.4% apraglutide vs 0% placebo; P = .006), something Joly described as a “dream” for these patients. By week 48, an additional 3 colon-in-continuity patients achieved enteral autonomy (12.5% apraglutide vs 7.4% placebo; P = .387).

Joly has relevant disclosures with Takeda, AbbVie, Jaansen, and 

Brooks, A. STARS: Apraglutide Reduces Parenteral Support in Patients with Stoma, Colon-In-Continuity. HCPLive. May 21, 2024. Accessed May 21, 2024. 

https://www.hcplive.com/view/stars-apraglutide-reduces-parenteral-support-in-patients-with-stoma-colon-in-continuity

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, IBS and IBD, Crohn's disease, and more.

Sivers-Teixeira explains that while the care team should quickly expand once dementia has presented in screening, the primary care role stays consistent.

Primary Care Roles in Alzheimer Diagnosis, with Theresa Sivers-Teixeira, MSPA, PA-C

 and dementia climb among the aging US population, the health care system is burdened by a limit on prospects for disease-altering therapy and means to do little more than delay the onset of progressive cognitive decline.

Even worse—as previously discussed with 

—is that the pipeline from primary and family care to specialists for a new dementia patient is long and arduous. It’s key that frontline clinicians know their role well in facilitating care at the first stages of dementia.

American Academy of Physician Associates (AAPA) 2024 Conference & Expo

 in Houston, TX, this week, Theresa Sivers-Teixeira, MSPA, PA-C, instructor of clinical medicine at Keck School of Medicine of University of Southern California, discussed the optimal role of primary care and physician associates specifically in managing new cases of dementia. As she explained, it’s not necessarily that the care team’s role changes with a potential diagnosis; PAs in particular have been trained holistically, and those skills come into immediate use.

“To me, when there's memory impairment, it's another chronic disease,” Sivers-Teixeira said. “It's a progressive chronic disease, and usually people who have cognitive impairment that evolves into Alzheimer's disease, at least 95% of them have at least 1 chronic disease, and then they gain more as the disease progresses. And that's not for the specialist so much.”

While specialists including neurologists, neurology-psychiatrists and other disease-specific caregivers focus on cognition-related health and prescribing strategies, primary caregivers should stay focused on supporting the needs of patients. But in their dynamic with specialists, Sivers-Teixeira said, the objective is to detect signs and symptoms and report them to specialists.

“We need to screen and we need to detect,” she explained. “And then we need to do the workup—we need to rule out the reversible causes. That's the very first thing that we need to do.”

They key to an effective referral is to fully ensure a complete workup on patients presenting with cognitive issues: other conditions, family history, attention to potential exacerbations or misdiagnoses, etc. As Sivers-Teixeira noted, patients with dementia risk face substantial wait time for not only treatment, but even just consultation, from a neurologist once a referral has been made.

“You've told this families on pins and needles that, oh my gosh, this could be a progressive dementing illness. They can't pick up the phone and call the specialists,” Sivers-Teixeira said. “We're the ones that are there on the front line. And then we communicate and do a good job, so that by the time they get to the specialist, they don't have to do all that stuff.”

Kunzmann K. How to Adequately Screen for and Treat Cognitive Decline in Primary Care. 

. Published May 20, 2024. https://www.hcplive.com/view/how-to-adequately-screen-treat-cognitive-decline-primary-care

Mattke S, Hanson M. Expected wait times for access to a disease-modifying Alzheimer's treatment in the United States. 

. 2022;18(5):1071-1074. doi:10.1002/alz.12470

Alzheimer Disease

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 and joined the MJH Life Sciences team in April 2021. He graduated from The College of New Jersey with a degree in Journalism and Professional Writing. He enjoys listening to records, going to concerts, and playing with his cat Squish. You can reach him at 

Both doses of guselkumab exhibited statistical superiority on all prespecified pooled endoscopic endpoints versus ustekinumab in Crohn's disease.

Inflammatory Bowel Disease

On the HCPLive inflammatory bowel disease page, resources on the topics of medical news and expert insight into IBD can be found. Content includes articles, interviews, videos, podcasts, and breaking news on IBD and more.

GALAXI 2 & 3: Guselkumab Superior to Ustekinumab for Crohn's Disease 

New STARS data were presented in a late-breaking abstract at DDW and build upon positive topline results for clinical responder rates and reductions in parenteral support.

STARS: Apraglutide Reduces Parenteral Support in Patients with Stoma, Colon-In-Continuity

This analysis may require further research to determine whether other treatment-resistant depression or severe depression definitions are specifically associated with inflammatory joint disease.

Rheumatoid Arthritis

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Bidirectional Link Identified Between Depression, Inflammatory Joint Disease

Feuerstadt breaks down findings from an ad hoc analysis of PUNCH CD3 and what the results suggest about the use of live-jslm (Rebyota) in patients taking concomitant medications.

Paul Feuerstadt, MD: Safety, Efficacy of Live-jslm in Patients Taking Concomitant Medications

During follow-up, rates of incident PAD were higher among patients with depressive symptoms compared with those without depression.

Depressive Symptoms Linked to Higher Risk of Peripheral Arterial Disease

Black men face significantly worse health outcomes in the US. Henry explains why the clinician needs to focus on building more authentic trust in their interactions.

Internal Medicine

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Aaron Henry, PA-C, MSHS: Regaining Black Male Patient Trust in the Doctor's Office

An assessment to improve colorectal screenings by shipping Cologuard kits to non-compliant patients proved beneficial for a Mayo Clinic research team.

Multitarget DNA Stool Testing Kits Could Reduce Colorectal Cancer Screening Non-Compliance

Patrick Campbell is the managing editor of HCPLive. Formerly the editorial lead of Endocrinology Network, Practical Cardiology, and Rheumatology Network, Patrick has spent years spearheading coverage surrounding cardiometabolic health and rheumatic disease for MJH Life Sciences. He now helps to lead coverage in each of these respective areas for HCPLive. Before joining MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA, and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

Patients with systemic autoimmune/inflammatory rheumatic diseases were nearly 3 times more likely to receive opioid prescriptions from 2006 to 2019.

Opioid Prescriptions Nearly 3 Times More Likely in Patients with Rheumatic, Autoimmune Diseases

These late-breaking data on drug candidate ENV-101 were presented at ATS 2024 and resulted from a new study on the drug’s effect on individuals with IPF.

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Toby Maher, MD, PhD: Improving Lung Function with ENV-101 Treatment of Idiopathic Pulmonary Fibrosis 

James R. Kilgore, DMSc, PhD, PA-C, discusses a new primary care screening tool for cognitive decline, plus lifestyle interventions that may complement drugs.

Neurology

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Latest News

Addressing Non-Adherence in Resistant Hypertension, with Swapnil Hiremath, MD, MPH

Focusing in on Novel Oral Systemic Therapies for Moderate Plaque Psoriasis: Medcast Video

Genetic Study Identifies Several Key Risk Factors Linked to Developing Psoriasis

Francisca Joly, MD, PhD: Apraglutide in Short Bowel Syndrome with Intestinal Failure

Primary Care Roles in Alzheimer Diagnosis, with Theresa Sivers-Teixeira, MSPA, PA-C