Digest 56, Cardiac Risk Calculators, Hypobaric Chambers and Alcohol, and So Much More

August 23, 2024 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue, we cover cardiac risk calculators, hypobaric chambers and alcohol, and so much more.   Effortlessly absorb important medical news, with our twice monthly newsletter featuring easily digestible analysis of the latest practice-changing articles, and of course…bad puns. 

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Issue 56

08/23/2024

Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two

Appetizers

Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels. 
-Beth Garbitelli MD, Beth Garbitelli MD; Laura Glick MD; Hannah Smith Md

• Drinking at Altitude–Dangerous? In a study recently published in Thorax, researchers at The Institute of Aerospace Medicine of the German Aerospace Center utilized a sleep lab and simulated in-flight sleep with a hypobaric chamber, set to mimic high altitude conditions. Participants spent two nights in the center and consumed approximately two alcoholic beverages prior to one of the nights, but not the other.  The combined exposure to both alcohol and higher altitude conditions decreased SpO2 and increased heart rate, with longer periods of clinical hypoxia than in those nights without both exposures. Both the combined exposure and the alcohol-only exposure significantly reduced deep sleep compared to the normal-pressure, no-alcohol exposure–with the greatest reductions in the combined group. (BG) 
• Mystery Non-Meat–Is that Plant-Based Diet Really So Healthy?  Plant-based diets are associated with numerous health and sustainability benefits, but ultra-processed vegetarian items such as plant-derived meat and dairy substitutes have also been making their way into common diets. In a new study just published in The Lancet Regional Health, researchers conducted a prospective cohort study of adults in the UK Biobank with complete dietary intake questionnaires filled out 4 times over the course of a year. Consumption was stratified based on animal versus plant and level of food processing (with the ultraprocessed, plant-sourced category including items such as packaged breads, soft drinks, reconstituted meat products, and pre-prepared frozen or shelf-stable meals). Higher intake of plant-sourced non-ultraprocessed foods was associated with lower risk of cardiovascular disease and mortality, but greater intake of plant-based *ultra processed* food was associated with increased risk of cardiovascular disease and mortality.  (BG) 
• Does HFNC in Acute COPD Exacerbations Work as well as NIV? In this non-inferiority, open label, randomized trial just published in Critical Care, researchers in China compared high flow nasal cannula (HFNC) to non-invasive positive pressure ventilation (NIV) in patients admitted to the ICU with acute exacerbations of COPD.  225 patients with moderate hypercapnic respiratory failure (pH 7.25-7.35 and PaCO2 >/= 50 mmHg) were randomized to receive NIV (such as BiPAP) or HFNC, if they had no contraindications to either.  In the intention-to-treat analysis, the treatment failure rate–defined as intubation or a switch to the other treatment type–was 11% higher with HFNC than with NIV, above the study’s noninferiority margin of 9%.  The rate of endotracheal intubation in the HFNC group was ~3x higher than in the NIV group (14.2% versus 5.4%, P=0.026). (HS) 
• Rash Concerns – Another reason to avoid overprescribing antibiotics?  In this population-based, nested case control study published in JAMA, researchers examined the risks of serious cutaneous adverse drug reactions (cADRs, such as DRESS Syndrome or SJS/TEN) after antibiotic use. The control cohort included adults > age 65 receiving >1 oral antibiotic prescription from 2002 – 2022. Patient cases, nested within the control population, also sought ED care or were hospitalized for serious cADRs within 60 days of antibiotic prescription. Almost 22,000 cases were identified, with a mean latency of 14 days, a 13% hospitalization rate, and a crude rate of 2.12 cADRs / 1,000 antibiotic prescriptions. The highest rates of cADRs occurred with cephalosporins and sulfonamides (4.92 and 3.22/1000 prescriptions, respectively). See this Figure for a full comparison of the risk of cADR by antibiotic class. (HS) 
• Another win for GLP-1 agonists! A double-blind, placebo-controlled, dose-finding phase II trial just published in NEJM looked at the effect of tirzepatide (a GLP-1 receptor and GIP receptor agonist) on metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis. 190 patients with biopsy-proven MASH with stage 2 (moderate) or stage 3 (severe) fibrosis were randomly assigned to receive subcutaneous injections of tirzepatide weekly (doses were 5, 10, or 15mg) vs. placebo for 52 weeks before undergoing repeat biopsy. At 52 weeks, a significantly greater percentage of patients receiving tirzepatide (at all three doses) had achieved MASH resolution without worsening of fibrosis compared to the placebo group (10% resolution with placebo vs 44% with 5 mg, 56% with 10 mg, and 62% with 15 mg tirzepatide, p<0.001 for all 3 comparisons). The proportion who achieved improvement of at least 1 fibrosis stage was also greater with tirzepatide than placebo. (LG)

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.

Given the consequences of climate change and extreme weather on public and individual health, medical schools have begun integrating these topics into their curricula and board questions, according to a recent article published in JAMA. For example, students at Harvard Medical School studying childhood asthma examined the impact of various types of environmental pollution on lung physiology and disease development. Similar curricula have extended beyond medical school into fellowship training on climate and health education and led to a professional network, The Global Consortium on Climate and Health Education, which offers free online certificate classes and resources for healthcare professionals. Experts in the field hope to educate clinicians about research on the health effects of the changing climate. 

– Jennifer DeSalvo MD

The Main Course

Jennifer DeSalvo MD

Battle of the Equations:

ASCVD Pooled Cohort vs PREVENT equations
Cardiovascular disease is a leading cause of death nationally, and atherosclerotic cardiovascular disease (ASCVD) risk estimation can help guide preventive therapy initiation and thereby decrease ASCVD-associated morbidity and mortality. The Framingham Risk Score was the first US guideline-recommended tool to estimate risk of heart disease, with the Pooled Cohort Equations (PCEs) subsequently introduced in 2013 and used since to estimate 10-year risk of ASCVD to guide initiation of primary prevention statin therapy.  

Over the last few years, clinicians have raised concerns that the PCEs might overestimate risk and be inadequately reflective of the changing US population (with underrepresentation of Latinx and Asian adults). In response to these concerns, the 2023 Predicting Risk of Cardiovascular Disease Events (PREVENT) equation was developed using individual-level data from 25 datasets, representing over 3 million individuals from 1992 – 2017. The PREVENT equation removed race and added renal function and statin use as variables, with optional variables for hemoglobin A1C, urine albumin-to-creatinine ratio, and zipcode (to estimate social deprivation index). In initial validation studies, the PREVENT equation risk estimates appeared to have improved accuracy and precision in the modern-day general population, also demonstrating lower risk estimates overall than the PCEs. And so began an (ongoing) debate about use of the PCEs versus PREVENT to determine ASCVD risk estimation and guide statin initiation for primary prevention. 

Breaking it down: 
In June 2024, JAMA Internal Medicine published a study comparing 10-year ASCVD risk estimates and recommendations for primary prevention statin therapy using the PCEs versus PREVENT.  Looking at risk among 3,785 adults aged 40-75 years without known cardiovascular disease, investigators concluded that mean 10-year ASCVD risk was significantly lower using PREVENT (4%) compared to the PCEs (8%) across all age, sex, and racial subgroups, and therefore, that the PREVENT equation might reduce the number of patients eligible for primary prevention statin therapy.  Another study published in July 2024 in JAMA sought to identify the clinical implications of the lower risk estimates provided by PREVENT. Using a nationally representative sample of 7,765 US adults aged 30-79 years, researchers estimated that utilization of the PREVENT equation would reclassify nearly half of US adults to lower ASCVD risk estimates and decrease the number of adults receiving or recommended for primary prevention statin therapy by 14.3 million, and antihypertensive therapy by 2.6 million. Researchers estimated that these reductions in treatment eligibility could result in ~107,000 additional myocardial infarction or stroke events, and that eligibility changes would affect significantly more men than women and more Black than White adults.

What does this mean?
These studies raise questions about what decision thresholds should be used for initiation of primary prevention therapy, both with the PCEs and the newer PREVENT equation. Furthermore, changing understanding of the population to which these equations are applied – as well as an evolving understanding of the risks and benefits of statins for primary prevention, including in a low risk population– has prompted ongoing re-evaluation of treatment and risk thresholds.  Guideline revisions will almost certainly be published in the near future that integrate the PREVENT equation with a reconsideration of what appropriate risk thresholds are in the modern day, in order to optimize the net clinical benefit of statin and nonstatin therapies for ASCVD risk reduction.  Some speculate that in optimizing benefit, treatment thresholds may in fact be lowered in future guidelines, to account for the overall safety of statin therapy and PREVENT’s lower risk estimates.  But in the interim, as this JAMA editorial elegantly summarizes, clinicians should continue to estimate ASCVD risk and decide about primary prevention statin initiation and continuation using the PCEs currently recommended by the ACC/AHA, given the harms of discontinuing appropriate preventive therapy.  While there is no “perfect” risk equation, both equations can help individualize risk estimation and guide discussions around primary prevention–now, with PREVENT, based on decades of data about cardiac risk that is better generalizable to the modern-day US population. 

Read The Latest JAMA Editorial Here!

Digestifs

Before you go….
we’ve got a few nibbles!

Consolidate your learning with a Quiz! 

This week on The Curbsiders: We’ve had a summer vacation on new content for the last month (soon much more to come!), but check out the REBOOT of episode #326, a 2022 NephMadness favorite, Cardiorenal Syndrome with all-star duo, Dr. Joel Topf and Dr. Sadiya Khan.  

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The Curbsiders Digest

Issue 56

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Disclosures:
Jennifer DeSalvo,  Laura Glick, Beth Garbitelli, Hannah Smith, and Nora Taranto report no disclosures.

Kate Grant reports no disclosures. 

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