Digest 63: Springing Forward To Coronary Calcium For CAD Risk Assessment?

March 21, 2025 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue, we discuss coronary calcium For CAD risk assessment, plus butter versus plant oils, treating both partners for BV, and Vitamin D in MS. It’s a packed March! 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 63

03/21/2025

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, Laura Glick MD, Alyssa Mancini MD, Hannah Smith MD

• Doubling Down on BV. Bacterial Vaginosis (BV) is a challenging common concern in primary care patients, often with frequent recurrences and frustrating symptoms. An open-label RCT published in NEJM offers a new paradigm to co-treat male partners of female patients with BV.  Standard of care first line treatment for female patients was compared to standard of care plus male partner treatment with oral metronidazole (twice daily x 7 days) and topical clindamycin to apply to the penis and foreskin (twice daily x 7 days). Couples were instructed to avoid sexual contact during the treatment period, and only women in a monogamous relationship with a male partner were eligible. Due to the reduction in BV recurrence with partner treatment at 12 weeks (35% recurrence rate in partner treated dyads versus 63% recurrence in female-only treatment, with an absolute reduction of -2.6 recurrences per person year), the study was stopped early! It is notable that the control group did not receive sham penile cream, due to concerns it might alter skin flora. (BG)
• Plant Oils: Better Than Butter?  In a recent prospective cohort study published in JAMA Intern Med, researchers analyzed dietary choices from >220,000 adults in the Nurses’ Health Study I/II and the Health Professionals Follow-up study using validated semiquantitative food frequency questionnaires administered every 4 years. Over 33 years, higher intake of butter was associated with an increased risk of total and cancer-related mortality, while a higher intake of plant-based oils was associated with a decreased risk of total, cancer-related, and cardiovascular disease mortality. Specifically, the highest amount of butter intake was associated with a 15% increase in total mortality. Higher intake of plant-based oils (especially olive, canola and soybean oils) was associated with a 16% decrease in total mortality compared to those with the lowest oil intake. Substituting 10g of butter with 10g of plant-based oils was associated with a 17% decrease in total mortality and a 17% decrease in risk of cancer-related mortality risk. (LG)
• ​​Can high-dose vitamin D D-Lay Multiple Sclerosis (MS)? JAMA recently published the results of the D-Lay MS trial, a parallel, double-blind RCT including 303 adults aged 18 to 55 years (median age 34 years, 70% women) who had untreated, recently diagnosed (< 90 days) clinically isolated syndrome (CIS) – a first episode of neurological symptoms suggestive of MS – and a serum vitamin D level < 100 nmol/L (40 ng/mL). Participants were randomized 1:1 to receive oral cholecalciferol 100,000 IU or placebo every 2 weeks for 24 months. Disease activity (a relapse and/or new or contrast-enhancing lesions on MRI over 24 months), was observed in 60.3% of vitamin D group participants and 74.1% of the placebo group (HR 0.66, 95% CI 0.50-0.87, p=0.004).  Median time to disease activity was longer in the vitamin D group compared with the placebo group (432 vs. 224 days, log-rank p=0.003). Secondary MRI outcomes (MRI activity, new lesions, contrast-enhancing lesions) all favored vitamin D, with no significant differences in the 10 secondary clinical outcomes (including relapse, though rates were low in both groups). There were no severe adverse events related to cholecalciferol. (AM)
• A Coffee A Day Keeps Kids’ Asthma Away. In this prospective cohort study recently published in Pediatric Allergy Immunology, researchers followed 5585 mother-child pairs from birth to 10 years of age to assess the relationship between maternal caffeine consumption and development of asthma in childhood.  Reports of caffeine consumption during pregnancy were obtained from admitted mothers within 72 hours of delivery.  Children were assessed for physician diagnoses of asthma and with spirometry/bronchodilation at 10 years of age. The study used nonlinear least squares models to estimate the knot point–i.e. the value of caffeine intake/day in which the association between caffeine and asthma reached a minimum value.  After adjusting for numerous confounders (including maternal smoking status, age, consumption of caffeine before pregnancy, maternal asthma, and sex of the child), the risk of asthma decreased with caffeine intake up to the knot point of 92.7mg of caffeine per day (adjusted OR 0.6, CI 0.41-0.88).  (HS)
• One blood thinner to rule them all? In this retrospective cohort study just published in JAMA Intern Med, researchers used Medicare claims to assess the comparative bleeding risk of warfarin, apixaban, or rivaroxaban being started in almost 5000 patients (age >50) with HIV and atrial fibrillation/flutter.  A majority (around 70%) were on antiretroviral therapy at the time of anticoagulant initiation. Researchers ultimately found a higher rate of major bleeding for patients started on warfarin compared to apixaban (Hazard Ratio 2.6), which increased substantially (to an HR of 6.7) in those receiving antiretroviral therapy.  There was also an increased risk of major bleeding for patients started on rivaroxaban compared to apixaban (HR 2.15), which similarly increased in patients also receiving antiretroviral therapy. The rates of major bleeding for rivaroxaban and warfarin were similar, and there were no differences in the rate of ischemic stroke or mortality across anticoagulants. (HS)

Palate Cleanser

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

As an Internal Medicine-Pediatrics resident working in the pediatric emergency department (ED) during the fall season, I vividly remember the teary-eyed elementary-aged children terrified of strep throat swabs and anxious teens with sports injuries. Thankfully, child life played an integral role in helping these young patients and their caregivers navigate their diagnostic evaluation and treatment, by distracting patients with toys, games, music, and breathing/meditation techniques. But what if there was an even better way to ease their anxiety? Enter therapy dogs! A recent clinical trial published in JAMA Network Open examined the impact of therapy dogs with child life among 80 children aged 5-17 years in a single academic pediatric ED randomized to either 10 minutes of exposure to a therapy dog with child life versus standard child life therapy. Interaction with therapy dogs led to a significantly greater reduction in child-reported and parent-reported child anxiety and a trend towards reduction in the use of chemical sedation compared to the control group. This study highlights the paws-itive role that therapy dogs can play in improving the patient experience!

– Jennifer DeSalvo MD

The Main Course

Jennifer DeSalvo MD

Coronary CT – A Crowning Achievement in CVD Risk Prevention?
Coronary artery calcium (CAC) scoring has emerged as a valuable tool to identify subclinical atherosclerosis and refine cardiovascular risk assessment in combination with traditional coronary artery disease (CAD) risk scores. CAC scores derived from computed tomography (CT) have been particularly helpful in individuals with intermediate risk and uncertainty about the benefits of statin initiation for primary prevention. However, no randomized clinical trials have evaluated whether primary prevention with lipid-lowering medications using CAC scores for guidance is associated with improved outcomes. The CAUGHT-CAD (Coronary Artery Calcium Score: Use to Guide Management of Hereditary Coronary Artery Disease) trial assessed whether combining discussions of CAC score with a prevention strategy could limit plaque progression in intermediate-risk patients with a family history of premature CAD.

Breaking it Down:
CAUGHT-CAD, just published in JAMA, was a randomized, open-label trial conducted at 7 hospitals in Australia. This study enrolled 365 asymptomatic, statin-naïve individuals aged 40-70 (mean age 58, 58% male) at intermediate risk of CAD (a.k.a. 0.4-3% annual risk using the Australian risk calculator) who had a family history of premature CAD (in a first-degree relative at under 60 or second degree relative <50).  Participants with coronary artery calcium (CAC) scores between 0-400 on baseline coronary CT angiography (CCTA) were randomized to CAC-score blinded usual care (standard education about CAD prevention and guideline-directed management), or CAC score-informed care (involving nurse-based discussion about CAD risk using CT images and CAC score, as well as initiation of statin therapy).  All participants had a follow-up CCTA at 3 years to determine longitudinal change in total plaque volume, which was the primary outcome of the study.

Plaque progression was greater in usual care than in the CAC score-informed group for total plaque volume (mean 24.9 mm³ with usual care vs 15.4 with CAC score-informed approach, between group difference of 9.5, p=0.009), noncalcified plaque volume, and fibrofatty and necrotic core plaque volume. These plaque volume changes persisted after adjustment for other risk factors including baseline plaque volume, blood pressure, and lipid profile. The CAC-score informed approach appeared to have the greatest benefit in those with CAC scores > 100.  There was a significantly sustained reduction in LDL-c (mean -2 with usual care vs -51 mg/dL with CAC-score informed strategy , p<0.001) levels at 3 years, and most individuals in the CAC arm remained on a statin at 3 years (152/179), compared to only 9 individuals in usual care who started a statin during this time. Those in the CAC arm had smaller increases in PCE risk equation scores over time (mean change of 2.1% over 3 years with usual care vs 0.5% with the CAC-score approach, p<0.001).

What does this mean?
Individuals at intermediate CAD risk with a significant family history had a significant reduction in plaque progression, decrease in cholesterol levels, and high levels of statin adherence with a CAC score-informed strategy compared to usual care–with greater benefit in those with higher CAC scores (>100).  By conventional criteria (ASCVD risk calculators), most of these individuals would not have met guidelines for statin therapy initiation.  The study has limitations, of course. Use of this technology is highly dependent on image quality, the primary outcome was a surrogate endpoint of plaque volume, not a clinical endpoint (though this endpoint has been associated with clinical outcomes, including in the REPRIEVE trial), and ultimately investigators found a reduction in the progression of plaques, not actual plaque regression.  It also remains unclear how much CAC score-informed education benefited patients specifically beyond the initiation of a statin medication (which occurred for all patients in the CAC arm)–though the high rates of statin adherence over time suggest it may well have.  

This study adds to the ongoing conversation (alongside evolving society guidelines) about how best to use CAC scoring–now, with more data to support its use in facilitating discussions around primary prevention when a patient’s overall risk is not captured using conventional risk calculators.  Several editorials put this article into context, with the ultimate aim of identifying the right population in which to use CAC scoring – to personalize conversations about risk and primary prevention, while also not using it “too early to effectively rule out risk, too late to influence decisions, and too often to yield clinically relevant information.”  

Read The Study Here!

Digestifs

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This week on The Curbsiders: In Episode #475, Dr. Avital O’Glasser highlights the perioperative pearls to know from the 2024 ACC/AHA guideline updates. From when to hold ACE inhibitors to the truth behind “NPO after midnight” to how to manage OSA around surgery, this episode is chock full of useful tips.   

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The Curbsiders Digest

Issue 63

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

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

Kate Grant reports no disclosures.  

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