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Cardiovascular Disease

Obesity Paradox Bias

The “obesity paradox” dominated last week’s cardiology news cycle after the British Medical Journal reported that obese patients with atrial fibrillation fared better than patients in a normal weight range. 

The authors used a registry of more than 52k patients recently diagnosed with AFib and at least one stroke risk factor and followed them for over two years. The primary endpoints were death, stroke, bleeding, and heart failure.

The authors found a U-shaped relationship between BMI and hard endpoints; both low and high BMI were positively associated with events. For example:

• Mortality was lowest for people in the “obese” range (BMI between 30-35 kg/m²) compared even with “normal-weight” or “overweight” BMI. 
• Mortality risk was highest for those who were “under-weight” and “severely obese.”
• For every 5 unit increase above 30 BMI, mortality risk increased by 16%.
• For every 5 unit decrease below 30 BMI, mortality risk increased by 32% (so 2x greater).

Reality Check

The findings suggest it is worse to be normal weight than to have a BMI in the obese range. Does this track? John Mandrola, MD (host of This Week in Cardiology) warns of collider bias—a subtype of selection bias—within the study.

To illustrate his point, he offers an example:

Say you are interested in researching the association between IQ and athletic ability. You decide to study students at an elite school, but to get into an elite school, you must be either extraordinarily smart or athletic. Following that logic, you will likely discover that athletes at elite schools have, on average, lower IQs than non-athletes. Consequently, you will find a (false) negative association between IQ and athleticism.

Mandrola argues that the recent BMJ study is also vulnerable to this bias. AFib patients with lower BMI must have had some AFib-causing condition other than obesity (e.g., cancer, pulmonary embolism, alcohol use disorder, etc.), and it’s likely that the AFib-causing comorbidity led to the worse outcomes observed in the lower weight group.

The Takeaway

When the authors of this study investigated the relationship between body mass index and AFib patient outcomes, they found an inverse relationship between BMI and all-cause mortality for patients with BMI under 30. Others pointed out that this study may suffer from collider bias, switching an unbiased harmful effect of obesity on mortality into a biased protective effect.

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The Wire

• A Closer Look at PVADs: Percutaneous left ventricular device (PVAD) use has skyrocketed over the last decade, becoming the most popular mechanical circulatory support device by 2018. But a new study found that PVAD implementation was not tied to lower mortality – although it was associated with higher cost. Researchers analyzed data from 80k PCI patients and identified large variation in PVAD utilization across markets (range: 0-85%). Although PVADs were not associated with lower mortality and were less likely to be used among the sickest patients, they had two times higher average hospital costs ($54k vs. $25k). 

• A New Clue into COVID’s Heart Impact: A new study suggests prior COVID infection may lead to reduced myocardial flow reserve (MFR) in patients with CV risk factors. When researchers compared PET scans of 101 patients previously diagnosed with COVID to 292 control patients (median duration from diagnosis to imaging: 191 days), the authors found a 20% decrease in the ability of coronary arteries to dilate. They also found that patients with prior infection were twice as likely to have reduced MFR (58% vs. 28%), which the authors state “is a marker for poor prognosis.”

• Supply Shortage Strain: Even Medtronic was not immune to supply shortages this quarter. In its recent Q1 earnings report, Medtronic noted revenues just over $7.37B – an 8% drop from what it took home this time last year – citing supply chain shortages as a primary culprit. Medtronic’s cardiac rhythm management portfolio saw revenues decrease by 6%, partially offset by modest growth in cardiac pacing therapies like leadless pacemakers. Despite the setbacks, the medtech giant still forecasts 4-5% revenue growth for the fiscal year. 

• Moderate Aortic Stenosis Mortality Nuances: A study in JACC indicates that many patients with moderate aortic stenosis may have a mortality risk that towers above the “moderate” epithet. Currently, physicians use echo-based assessments of peak velocity, mean pressure gradient, and aortic valve area to diagnose moderate AS, and ideally, all of these measurements will fall within a range that coincides to one grade. But when researchers investigated nearly 2,000 patients with moderate AS, 40% had “discordant grading.” These discordant grading patients showed significantly higher mortality rates than those with concordant moderate AS (P < 0.001).  

• CathVision’s $7.2M Round: Electrophysiology technology developer CathVision announced the close of a $7.2M financing round last week. CathVision’s EP recording system ECGenius uses proprietary hardware to capture clean EP signals with minimal baseline noise to provide electrophysiologists with automated analysis during cardiac ablation procedures. The fresh funding will help the startup commercialize the device, as well as develop modules that provide electrophysiologists with automated analysis during cardiac ablation procedures. 

• New CHEST Guidelines: The American College of Chest Physicians released 44 updated recommendations for perioperative management of antithrombotic therapy. The guideline recommendations incorporated new evidence regarding patients taking vitamin K antagonists such as warfarin, heparin bridging, antiplatelet drugs, and direct oral anticoagulants. 

• Gene Variant Protects Against CHD: People with a mutation in their MFGE8 gene, which encodes a protein that contributes to arterial stiffness, may have protection against coronary atherosclerosis. Using data from the Finish biobank (n = 260k), researchers found that the risk of developing heart disease is about one fifth lower in those who carry the MFGE8 variant compared to the general population. They speculate that the variant carriers’ below-average artery stiffness is likely responsible for the protective effect, and hint that inhibiting production of the protein encoded by MFGE8 may help prevent coronary heart disease.

• 88,000 Cardiac Devices Recalled: The FDA announced that Medtronic is recalling nearly 90k implantable cardiac devices due to risk of serious injury or death. The Class I recall includes Medtronic’s Cobalt XT, Cobalt and Crome implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy defibrillators (CRT-Ds). They were distributed to customers from February 2020 to the present day.

• Atrial Cardiopathy & Dementia Risk: A new study in JAHA suggests older adults with atrial cardiopathy may have at least 35% higher risk for dementia. Researchers conducted a prospective analysis of 5k participants over 5-8 years and found that atrial cardiopathy was significantly associated with dementia (hazard ratio: 1.35). While the study is observational and cannot make a causal link, the authors suggest that abnormalities in left atrial structure or function may be an independent risk factor for dementia. 

• EchoNous & Samsung Tablets Connect: A new alliance between Samsung and cardiac-focused ultrasound startup EchoNous allows clinicians to use the Kosmos handheld ultrasound system with Samsung’s Galaxy Tab Active Pro tablets, rather than being bound to EchoNous’ Kosmos Bridge display. The Kosmos system can integrate ECG, stethoscope, and ultrasound signals to diagnose, educate, and train at the point of care. The new compatibility will lower the Kosmos platform’s overall cost, which is already “tens of thousands of dollars less” than cart-based competitors. 

• First Precision Medicine RPM: MediCardia Health is partnering with Human Longevity to deploy what it calls “the nation’s first remote platform for precision medicine,” which allows the progression of cardiovascular disease to be tracked remotely so that treatments can be optimized around improving longevity. MediCardia’s HeartChart platform combines remotely gathered vital signs with clinical data from the EHR to synthesize complete patient profiles that can proactively identify those at risk of cardiac events.

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