Dr. Stephen Chanock, on the use of drugs to block TGF-beta in men who lose their Y chromosome.

Cardiogenetics

Why Men Die Earlier

A study published in Science found that the loss of the Y chromosome, which occurs naturally in many men as they age, can cause heart scarring and premature death.

Scientists have known for half a century that the Y chromosome can disintegrate over time, but they weren’t sure if the downstream consequences mattered. 

New research from the University of Virginia suggests that the consequences of a degrading Y chromosome definitely matter. When researchers genetically removed the Y chromosome from the white blood cells of mice, they found that:

• The mice died earlier and with more cardiac fibrosis.
• Heart function was restored by treating the mice with a drug that blocks heart scarring. 

To tie these findings to human men, the researchers analyzed genetic data from the UK Biobank (223k men) and found that:

• Men with a mosaic loss of the Y chromosome had a 41% increased risk of dying from any cause during a 7-year follow-up, and a 31% increased risk of dying from cardiovascular disease. 
• These men were two to three times more likely to die of congestive heart failure or heart disease.
• As Y chromosome loss increased, so did the risk of dying from CVD. 

A drug that may help counter the Y loss-associated heart scarring is already on the market. FDA-approved pirfenidone is used to treat idiopathic pulmonary fibrosis, a form of lung scarring, and has undergone trials for heart failure. The study’s authors note that men with Y loss may have a “superior response to this class of therapeutic agents,” although this has not been tested directly yet. 

The Takeaway

These findings demonstrate that Y chromosome loss can directly contribute to age-related heart disease through tissue scarring, and suggest that targeting the effects of Y chromosome loss could help men live longer, healthier lives. 

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The Wire

Caption & HeartBeat’s Virtual Pathway: Ultrasound AI startup Caption Health unveiled a new partnership with virtual cardiology company HeartBeat Health, enabling early disease identification and management for patients from the comfort of their homes. This is an expansion of its Caption Care program, which began when Caption partnered with Portamedic to allow Portamedic technicians to perform AI-guided echo exams in patient homes. With the addition of HeartBeat’s remote cardiologists, it appears that Caption has established a complete virtual echo pathway. 

Home Care Preferences: Speaking of home care, a Cross Country Healthcare survey of 500 US residents between 50 and 79 years of age found that 70% would prefer to age at home rather than go to a retirement community or nursing home. Despite a growing preference for home care, only 9% said they’re actively looking into their future health needs, citing reasons such as not having any health issues (51%), purposely avoiding thinking about it (30%), or not being able to afford it (27%).

Directional Beats Orbital Atherectomy: New York-based researchers found that the directional atherectomy system (DAS) may be superior to the orbital atherectomy system (OAS) in treating patients with peripheral arterial disease (PAD). Results from 60 patients who underwent either DAS or OAS showed that DAS led to greater plaque volume reduction (5.9% vs. 1.1%), a greater increase in lumen volume (179mm3 vs. 48mm3), and a reduction in angiographic stenosis (40% vs. 70%). DAS also required significantly fewer stents after drug-coated balloon angioplasty (2 patients vs. 10 patients).

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Sleep Inducers & CV Risk: A retrospective study out of Japan found no relationship between the use of sleep-inducing medication and major adverse cardiac events. Researchers used data from 23k patients (average follow-up: 879 days) and found that patients who were prescribed sleep aids were not at higher risk of death (4% vs. 3.4%), MACE (6.3% vs. 6.5%), or HF events (6.6% vs. 5.4%). 

Exceeding Exercise Guidelines: A new Circulation paper found that exceeding current exercise recommendations, up to a point, may extend one’s life. The current guidelines advise exercising moderately for 150 to 299 mins/week and vigorously for 75-149 mins/week. New research from 116k US adults followed for 30 years showed that people who exercised two to four times the recommended minimum saw the greatest mortality benefits (2-13% lower mortality). However, those who exercised more than four times the minimum saw no further benefits. 

Patient Data Privacy: An AMA survey of 1k adult patients found that 92% think corporations shouldn’t be able to purchase their health data, although most feel comfortable sharing data with their physician and health system (75% & 64%). The vast majority of patients also want health app developers to disclose how their products handle patient data (93%) and want their providers to review app security before granting it access to their data (88%), while most also want to be able to opt-out of having their health data shared (80%).

BMI’s AFib Impact: This paper published in JACC found that differences in BMI may primarily drive the association between low cardiorespiratory fitness (CRF) and AFib. Among 18.5k participants without AFib, higher midlife BMI was associated with higher AFib risk independent of CRF levels and other baseline risk factors (hazard ratio: 1.05). There was no association between lower midlife CRF AFib risk after the researchers adjusted for BMI. The participants were mostly White and men (98% & 79%) from a high socioeconomic class, so these findings may not be generalizable. 

USPSTF Recommends Counseling: The US Preventive Service Task Force (USPSTF) is again recommending clinicians refer select adults without CVD risk factors to behavior counseling to encourage healthy lifestyle changes. USPSTF reviewed 113 randomized clinical trials (30k adults without CVD risk factors) with a minimum 6-month follow-up, and determined with “moderate certainty” that behavioral counseling interventions have a “small net benefit” on CVD risk. 

Absolute Coronary Flow Value: A Nature-published study showed that fractional flow reserve (FFR) accurately predicted actual coronary blood flow (CBF) changes. The researchers compared fractional CBF with absolute CBF (aCBF) in 203 diseased arteries (143 patients) and found a substantial correlation between the two measurements (r=0.89). The concordance was highest when FFR was above 0.80 and below 0.70 and poorest in the 0.75–0.80 range. The authors note that aCBF complements FFR and may help accurately assess CBF. 

Siemens ARTIS icono ceiling Cleared: Siemens Healthineers announced the FDA clearance of its ARTIS icono ceiling Angiography System, joining its ARTIS icono biplane and floor systems. The new ARTIS icono ceiling is intended for interventional cardiovascular and radiology procedures, and is highlighted by its “superfast” second cone beam CT acquisitions (reduces motion artifacts & contrast dose), OPTIQ image chain processing technology (increases image quality, allows lower dosage) and Case Flows workflows (reduces user interaction, setup times).

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