What Risk Factors are Associated with Progressive Hearing Loss?
BACKGROUND AND PURPOSE:
- Dillard et al. (JAMA Network Open, 2025) examined the 25-year cumulative incidence and progression of hearing loss and related risk factors
METHODS:
- Population-based cohort study
- Framingham Offspring Study
- Population
- Individuals in Framingham, MA with data from hearing examinations
- Exposures
- Age | Sex | Education | Noise exposure history | Smoking and heavy drinking
- Measured hypertension | Stroke risk (Framingham Stroke Risk Profile [FSRP]) | Low-density lipoprotein | High-density lipoprotein | Total cholesterol | Fasting blood glucose | Systolic and diastolic blood pressure | Waist circumference
- Study design
- Hearing defined by worse-ear pure-tone average (PTA) of thresholds at frequencies
- 0.5 | 1.0 | 2.0 | 4.0 kHz
- Logistic and linear regression models were used to determine exposures associated with outcomes
- Adjustment for sex and age
- Hearing defined by worse-ear pure-tone average (PTA) of thresholds at frequencies
- Primary outcome
- Hearing loss
- Defined as PTA more than 25 dB HL
- Hearing loss progression
- Annualized increase in PTA
- Hearing loss
RESULTS:
- 511 participants
- Male: 41.5%
- 25-year cumulative incidence of hearing loss: 56.2%
- Mean hearing loss progression: 51.1 (SD, 11.6) dB
- Factors associated with incident hearing loss
- Older age
- Lower education
- High noise exposure
- Among participants aged >50 years
- Hypertension | Higher FSRP
- Factors associated with hearing loss progression
- Older age
- Female sex
- Lower education
- Among participants aged >50 years
- Hypertension | Higher diastolic BP
CONCLUSION:
- The 25-year cumulative incidence of hearing loss among aging adults was 56%
- Cardiovascular factors, such as elevated stroke risk (FSRP), hypertension, and higher diastolic blood pressure, were linked to the onset or progression of hearing loss in participants >50 years at baseline
- The authors state
Results from this study corroborate hearing loss as a common public health concern that may be at least partially preventable and provide important information regarding the incidence and natural history of hearing loss
Learn More – Primary Sources:
The 25-Year Incidence and Progression of Hearing Loss in the Framingham Offspring Study
Semaglutide and Cardiovascular Outcomes: Is Weight Loss the Only Factor?
BACKGROUND AND PURPOSE:
- In the SELECT trial, semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) reduced major cardiovascular events (MACE) in patients with obesity and preexisting cardiovascular conditions in participants without diabetes
- Deanfield et al. (The Lancet, 2025) examined whether factors beyond weight loss and waist circumference contribute to reductions in MACE risk
METHODS:
- Prespecified secondary analysis of a randomized, double-blind, placebo-controlled trial
- SELECT trial
- 41 countries
- Participants
- Individuals ≥45 years
- BMI ≥27 kg/m2
- Interventions
- Once-weekly semaglutide with target dose of 2.4 mg
- Placebo
- Exposures
- Adiposity change in the first 20 weeks | 104 weeks
- Study design
- Adiposity measures included weight and waist circumference
- Primary outcome
- Risk of MACE after 20 weeks
- Composite: Cardiovascular death | Non-fatal myocardial infarction | Non-fatal stroke
- Risk of MACE after 20 weeks
RESULTS:
- 17,604 patients in SELECT
- Semaglutide reduced the incidence of MACE compared to placebo, regardless of baseline weight and waist circumference
- Within the semaglutide group, lower baseline bodyweight and waist circumference were associated with a lower incidence of MACE
- Reduction in risk per 5 kg lower bodyweight
- Hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.99) | P=0.001
- Reduction in risk per 5 cm smaller waist circumference
- HR 0.96 (95% CI, 0.93 to 0.99) | P=0.004
- Reduction in risk per 5 kg lower bodyweight
- In the placebo group, lower baseline waist circumference but not bodyweight was associated with a lower MACE risk
- Lower baseline waist circumference
- HR 0.96 (95% CI, 0.94 to 0.99) | P=0.007
- Lower baseline bodyweight
- HR 0.99 (95% CI, 0.97 to 1.01) | P=0.28
- Lower baseline waist circumference
- In the placebo group, weight loss was paradoxically associated with increased MACE risk
- In those receiving semaglutide there was no linear trend linking weight loss at week 20 to subsequent MACE risk
- Greater waist circumference reduction at week 20 was associated with lower subsequent MACE risk
- The observed benefit on MACE was mediated through waist circumference reduction, though this was minimized after adjustment for time-varying changes in waist circumference
- HR 0.86 (95% CI, 0.77 to 0.97)
CONCLUSION:
- Semaglutide lowered cardiovascular risk independent of early weight loss, although there was a linear relationship associated with decreasing waist circumference
- The authors state
This supports the reconceptualisation of GLP-1RAs as potential cardiovascular disease-modifying agents, with implications for clinical practice and health-care policy
Learn More – Primary Sources:
17 Years Later: Evaluating the Impact of the HPV Vaccine on Cancer Rates
BACKGROUND AND PURPOSE:
- While clinical trials showed the HPV vaccine is highly effective, its real-world impact especially among high-risk adolescents and young women is less well understood
- DeSieghardt et al. (JAMA Pediatrics, 2025) examined effectiveness and herd protection in this high-risk population over the first 17 years following HPV vaccine introduction
METHODS:
- Cross-sectional study
- Data from 6 surveillance studies from 2006 to 2023
- Population
- A consecutive sample of sexually experienced adolescent girls and young women aged 13 to 26 years
- Exposure
- HPV vaccination status
- Defined as receipt of ≥1 vaccine dose
- HPV vaccine type
- 2-valent vaccine (2vHPV) | 4-valent vaccine (4vHPV) | 9-valent vaccine (9vHPV)
- HPV vaccination status
- Study design
- The prevalence of vaccine-type HPV was compared in vaccinated participants from studies 2 through 6, vs unvaccinated participants in study 1
- Inverse probability of treatment weighting with propensity score was used to balance comparison groups
- Primary outcomes
- Herd protection
RESULTS:
- 2335 participants
- African American: 65.4% | Asian: 0.6% | Native American: 0.3% | White: 24.9% | Multiracial: 6.5% | Hispanic: 7.4%
- Reported a STI history: 51.2% | Reported ≥2 male sex partners: 78.9%
- Vaccination rates increased from 2006 to 2023
- 2006: 0% | 2023: 82.1%
- Among vaccinated participants, positivity for HPV types decreased between 2006 and 2023
- 2vHPV studies
- 2006: 27.7% | 2023: 0.4%
- Relative difference 98.4%
- 4vHPV studies
- 2006: 35.4% | 2023: 2.1%
- Relative difference 94.2%
- 9vHPV studies
- 2006: 48.6% | 2023: 11.8%
- Relative difference: 75.7%
- 2vHPV studies
- Positivity for different HPV types also decreased among unvaccinated participants, though gains were smaller than vaccinated participants
- 2vHPV studies
- 2006: 25.8% | 2023: 7.3%
- Relative difference: 71.6%
- 4vHPV studies
- 2006: 25.3% | 2023: 6.1%
- Relative difference: 75.8%
- 9vHPV studies
- 2006: 42.7% | 2023: 31.3%
- Relative difference: 27.2%
- 2vHPV studies
- There were significant reductions in the odds of at least 1 HPV type for 2vHPV, 4vHPV and 9vHPV studies
- 2vHPV studies
- All participants: Adjusted odds ratio (aOR) 0.03 (95% CI, 0.01 to 0.07)
- Vaccinated participants: aOR 0.01 (95% CI, <0.01 to 0.05)
- Unvaccinated participants: aOR 0.23 (95% CI, 0.08 to 0.63)
- 4vHPV studies
- All participants: aOR 0.06 (95% CI, 0.03 to 0.10)
- Vaccinated participants: aOR 0.04 (95% CI, 0.02 to 0.08)
- Unvaccinated participants: aOR 0.19 (95% CI, 0.07 to 0.52)
- 9vHPV studies
- All participants: aOR 0.22 (95% CI, 0.16 to 0.31)
- Vaccinated participants: aOR 0.14 (95% CI, 0.09 to 0.21)
- 2vHPV studies
CONCLUSION:
- 17 years after the introduction of HPV vaccination, population-level vaccine effectiveness and herd immunity remain high
- The authors state
Our findings provide new evidence of robust effectiveness and herd protection in sexually experienced adolescent girls and young women at relatively high risk of HPV and associated cancers, even if they did not receive the recommended 2- or 3-dose vaccine series
Learn More – Primary Sources:
Population-Level Effectiveness and Herd Protection 17 Years After HPV Vaccine Introduction
Do LLMs Reason as Well as Attending Physicians?
BACKGROUND AND PURPOSE:
- It is challenging to measure large language model (LLM) performance on tasks requiring reasoning
- Script Concordance Testing (SCT) is a way to measure how well decisions can be adjusted when new information becomes available
- McCoy et al. (NEJM AI, 2025) created a SCT benchmark for LLM assessment to assess reasoning capabilities of these algorithms vs medical professionals
METHODS:
- Public benchmark of 750 SCT questions
- Drawn from 10 international, diverse datasets (9 newly releases) across multiple specialties
- SCT benchmark
- Each item presents a clinical vignette
- Data is added and the model is asked how the added data changed the likelihood of a diagnosis or management option
- Model performance is scored against expert-panel responses
- Assessed
- 10 state-of-the-art LLMs
- 1070 medical students
- 193 residents
- 300 attending physicians
RESULTS:
- Overall, LLMs showed markedly lower performance on the SCT than they usually show on medical multiple-choice benchmarks
- Across prompting conditions, OpenAI’s o3 achieved the highest performance
- OpenAI’s o3: 67.8% (SD, 1.2)
- GPT-4o: 63.9% (SD, 1.3)
- OpenAI’s o1-preview: 58.2% (SD, 1.3)
- DeepSeek R1: 55.5% (SD, 1.4)
- Google’s Gemini 2.5 Pro Preview: 52.1% (SD, 1.4)
- Reasoning-optimized models matched or exceeded student performance on multiple examinations but did not reach the level of senior residents or attending physicians
- Response-pattern analysis showed systematic overconfidence
- Reasoning-tuned models overused strong, definitive answers
- This suggests that training AI to explain its thinking step-by-step might actually make it less flexible when dealing with uncertain medical situations
CONCLUSION:
- Even among LLMs explicitly tuned for reasoning, SCT found that the clinical reasoning these models could display was limited
- The authors state
Our analysis of model response patterns reveals that even state-of-the-art LLMs exhibit striking overconfidence, disproportionately favoring extreme belief shifts and failing to recognize when new information should not alter clinical hypotheses
Learn More – Primary Sources:
Assessment of Large Language Models in Clinical Reasoning: A Novel Benchmarking Study
RCT Results: Lower Dose Oral Semaglutide Weight Loss Treatment for Obesity and Overweight
BACKGROUND AND PURPOSE:
- The OASIS 1 Trial found that 50 mg oral semaglutide reduced body weight and cardiovascular risk in individuals with overweight and obesity
- A dose of 25 mg may also be appropriate for this population
- Wharton et al. (NEJM, 2025) evaluated the efficacy and safety of a lower 25 mg oral semaglutide dose for participants with overweight or obesity
METHODS:
- 71-week, double-blind, randomized, placebo-controlled trial
- OASIS 4 Trial
- 22 sites in four countries (Canada, Germany, Poland, and the US)
- Participants
- Without diabetes
- BMI ≥30 or BMI ≥27 with at least one obesity-related complication
- Interventions
- Oral semaglutide, 25 mg, once daily
- Placebo
- Study design
- All participants were counseled in lifestyle interventions
- Primary outcomes
- Percent change in body weight at week 64
- Reduction of 5% or more in body weight
- Secondary outcomes
- Reductions in body weight of ≥10% | ≥15% | ≥20%
- Change in the Impact of Weight on Quality of Life–Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score
RESULTS:
- Oral semaglutide: 205 | Placebo: 102
- There was a significantly greater mean change in body weight at week 64 in the oral semaglutide group
- Oral semaglutide: –13.6% | Placebo: –2.2%
- Estimated difference, −11.4 percentage points (95% CI, −13.9 to −9.0) | P<0.001
- Participants in the oral semaglutide group were significantly more likely than those in the placebo group to have body-weight reductions of ≥5%, ≥10%, ≥15% and ≥20% (P<0.001 for all comparisons)
- Those who received oral semaglutide also had improved IWQOL-Lite-CT Physical Function score (P<0.001)
- Gastrointestinal adverse events were more common with oral semaglutide
- Oral semaglutide: 74.0% | Placebo: 42.2%
CONCLUSION:
- For individuals with overweight or obesity and without diabetes, once daily oral semaglutide (25 mg) led to significantly greater body weight reduction vs placebo
- The authors state
In our trial, oral semaglutide at a dose of 25 mg once daily led to a clinically relevant mean reduction in body weight of 13.6%
Almost a third of the participants in the oral semaglutide group had a reduction in body weight of 20% or more
Learn More – Primary Sources:
Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity
Does Regular Brisk Walking Reduce Mortality Risk in Low-Income, Predominantly Black Populations?
BACKGROUND AND PURPOSE:
- Liu et al. (American Journal of Preventative Medicine, 2025) investigated the effects of factors like walking pace on mortality, including in low-income and Black populations
METHODS:
- Secondary analysis of a prospective cohort study
- Data from Southern Community Cohort Study (please see ‘Learn More – Primary Sources’ on details regarding this study)
- 12 southeaster US states | Recruitment mostly from community health centers
- Between 2002 and 2009
- Predominantly low-income and Black (approximately 70%)
- Participants
- Adults
- 40 to 79 years
- Exposures
- Walking pace and duration
- Demographic info
- Lifestyle factors
- Primary outcome
- Mortality
RESULTS:
- 85,000 adults
- Median follow-up: 16.7 years
- Deaths: 26,862
- There was a significant link between daily fast walking for as little as 15 minutes a day and lower all-cause mortality
- Hazard Ratio (HR) 0.81 (95% CI, 0.75 to 0.87)
- Daily slow walking of even >3 hours was only associated with a modest reduction in risk
- HR 0.96 (95% CI, 0.91 to 1.00)
- Fast walking was associated with reduced mortality, independent of leisure-time physical activity levels
- The inverse association was more pronounced for mortality due to cardiovascular diseases than cancers
- While all groups benefitted from fast walking, participants with baseline comorbidities showed larger risk reductions compared to generally healthy participants
CONCLUSION:
- Even 15 minutes of fast walking daily was associated with reduced risk of all-cause mortality in a diverse population and can be effective in reducing health disparities
Learn More – Primary Sources:
Daily Walking and Mortality in Racially and Socioeconomically Diverse U.S. Adults
Southern Community Cohort Study (SCCS)
Clinical Practice Guideline on Benzodiazepine Tapering
SUMMARY:
Benzodiazepines (BZDs) are FDA-approved medications frequently prescribed for anxiety disorders, panic disorders, social phobia, insomnia, and seizures. As patients age or as their health status and other medications change, the risk–benefit ratio of continued benzodiazepine use may shift. Physical dependence is an expected consequence of regular use, and discontinuing BZDs can be challenging. Abruptly stopping BZDs or reducing the dose too quickly can result in serious and potentially life-threatening withdrawal symptoms.
Benzodiazepine tapering is a patient-centered, gradual process for discontinuing medications associated with dependence, withdrawal risk, and significant harms e.g., increased likelihood of falls, motor vehicle accidents, cognitive impairment, delirium, overdose, death when used long-term. Tapering is indicated when risks outweigh benefits, with abrupt discontinuation strongly discouraged due to the risk of withdrawal and serious adverse events. The 2025 Joint Clinical Practice Guidelines on Benzodiazepine Tapering developed by ASAM and 9 other medical and professional societies advises individualizing the pace and duration of the taper to optimize safety and minimize withdrawal symptoms.
Key Considerations
- Clinicians should regularly reassess benzodiazepine use, ideally at least every 3 months, to weigh ongoing risks and benefits.
- Review prescription drug monitoring programs for all benzodiazepine renewals or new prescriptions.
Evaluate for physical dependence | duration and dosage | SUD | psychiatric or medical comorbidities e.g., OSA, COPD
- Do not abruptly discontinue in physically dependent patients; assess for special circumstances requiring referral (substance misuse, high doses, or unstable conditions)
- Assess for signs of benzodiazepine dependence and withdrawal risk—patients with prolonged| high-dose use| comorbidities e.g., need slower, monitored tapers.
- Identify patients with co-occurring substance use disorders, as these individuals may require coordinated care, harm reduction, and possibly higher levels of medical supervision.
- Differential includes differentiating between withdrawal symptoms, recurrence of original anxiety or insomnia symptoms, and acute psychiatric or medical conditions
- Engage patients collaboratively in their taper plan to enhance adherence and safety
Implementing Deprescribing
- First-line: gradual dose reduction by 5–10% every 2–4 weeks, not exceeding 25% in any 2-week period; personalize based on patient response
- Those on lower doses for less than 3 months may taper more rapidly, while patients with longer or higher-dose exposure may need months or years to complete a taper
- Switching to a longer-acting benzodiazepine is not routinely necessary and should only be considered if needed for dose manipulation or patient comfort
- Monitor for withdrawal symptoms during each dose reduction; pause or slow tapers as needed to maintain safety.
- For Z-drugs (zolpidem, zopiclone), use a similar approach; both short- and long-term users are at risk for withdrawal.
- Adjunctive strategies may include psychosocial interventions, cognitive-behavioral therapy, and addressing co-occurring psychiatric or substance use disorders.
- Refer for specialist support or a higher level of care when complications or safety concerns arise.
Follow Up
- Reassess withdrawal symptoms, mental and physical health, and overall progress at every tapering visit, with frequency based on clinical risk and phase of taper.
- Engage patients in assessing readiness for further dose reduction or need to pause the taper.
- Provide ongoing support, education on harm reduction, and access to adjunctive therapies for withdrawal or relapse prevention.
KEY POINTS
- Tapering benzodiazepines requires gradual, individualized reductions, with 5–10% dose decreases every 2–4 weeks favored as standard practice
- Clinicians must not abruptly discontinue benzodiazepines in physically dependent individuals and should monitor closely for withdrawal
- Patient engagement and shared decision-making are essential for successful outcomes
- Specialist referral is recommended for complex cases (substance use disorder, high-dose use, adverse withdrawal) or treatment difficulty
- The overall goal is improved safety, reduced harm, and restoration of patient quality of life
Learn More-Primary Sources
How Have BCRA Genetic Testing Rates Changed in the Past Decade?
BACKGROUND AND PURPOSE:
- BRCA testing utilization increased between the mid 2000s and mid 2010s, in line with 2005 USPSTF recommendations that called for genetic testing of those with a family history
- Testing recommendations have expanded in recent years, with new USPSTF recommendations in 2019 recommending testing for a wider population
- The recent impact of new testing guidelines, as well as new testing technologies, on BRCA testing utilization has not been studied
- Shi et al. (Genetics in Medicine, 2025) evaluated the utilization of BRCA testing using US MarketScan claims data from 2013 to 2022 for women and men aged 18 to 64 years
METHODS:
- Population-based study
- Data from US MarketScan Commercial Database
- Population
- 18 to 64 years
- Continuously enrolled in capitated or noncapitated plans for ≥1 year
- Exposures
- Year
- Sex
- Indications for testing
- Study design
- Average annual growth rates of utilization were estimated by regressing the natural logarithm of utilization rates on the calendar year
- Primary outcomes
- Annual utilization rates of BRCA testing overall and by BRCA test type
- Median expenditures per enrollee
- Percentage of 0 out-of-pocket expenditures
RESULTS:
- Annual BRCA testing utilization among women and men increased every year between 2014 and 2019
- Women
- 2014 to 2015: 10.2% per year
- 2016 to 2019: 10.0% per year
- Men
- 2014 to 2015: 44.5%
- 2016 to 2019: 44.8%
- Women
- Testing decreased in 2020
- Women: 34.4%
- Men: 44.8%
- Annual testing rates rebounded each year during 2021 to 2022, though they remained below pre-pandemic levels
- Women: 8.5%
- Men: 22.3%
- Median expenditures for comprehensive BRCA testing per enrollee decreased from 2013 to 2022: 68%
- Most of these enrollees had 0 out-of-pocket expenditures
- Most BRCA testing was performed on individuals
- With family cancer history: Breast | Ovarian | Prostate
- Among women 18 to 50 years
CONCLUSION:
- The BRCA testing rate has modestly increased annually despite more expansive guidelines and decreasing out of pocket costs
- The authors state
These findings have implications for the need to educate health providers, including primary care providers and public health programs, as well as health insurers, about current BRCA testing eligibility criteria, recent reductions in costs, and the benefits of testing to inform interventions for cancer prevention and earlier detection for their patients
Learn More – Primary Sources:
How Robust are Large Language Models in the Medical Setting?
BACKGROUND AND PURPOSE:
- AI chatbots can accurately answer medical questions that reflect those found in benchmark medical question and answer sets such as MedQA
- It is unclear if large language models (LLMs) will also perform as well when confronted with cases that require more complex reasoning where there are new patterns to address
- Bedi et al. (JAMA Network Open, 2025) evaluated both reasoning and standard LLMs to determine whether reasoning capabilities improve robustness in medical settings
METHODS:
- Cross-sectional study
- Exposures
- 6 LLMs
- DeepSeek-R1 | o3-mini | Claude-3.5 Sonnet | Gemini-2.0-Flash | GPT-4o | Llama-3.3-70B
- 6 LLMs
- Study design
- 100 questions from MedQA were sampled
- The original correct answer choice was replaced with “none of the above” (NOTA) such that the answer was no longer in the answer multiple-choice set
- All models were asked to provide chain of thought answers
- Primary outcome
- Accuracy (percent of answers correct)
RESULTS:
- The accuracy of all 6 models decreased when questions were modified with NOTA answers
- Relative accuracy among the models decreased between 8.82% (Deep-Seek-R1) and 38.24% (Llama-3.3-70B)
- The Deep-Seek-R1 and o3-mini models (“reasoning” models) were more resilient to the decrease in accuracy, but all experienced a significant drop in accuracy with NOTA answers inserted
CONCLUSION:
- The ability of LLMs to accurately answer MedQA questions decreased when the correct answer was replaced with “none of the above”
- This demonstrates gaps in accuracy that exist when pattern disruption occurs
- The authors state
When forced to reason beyond familiar answer patterns, all models demonstrate declines in accuracy, challenging claims of artificial intelligence’s readiness for autonomous clinical deployment
A system dropping from 80% to 42% accuracy when confronted with a pattern disruption would be unreliable in clinical settings, where novel presentations are common
Learn More – Primary Sources:
Fidelity of Medical Reasoning in Large Language Models
Could Postoperative Radiotherapy Be Safely Omitted in Older Women with Low-Risk Breast Cancer?
BACKGROUND AND PURPOSE:
- Palmér et al. (JNCI: Journal of the National Cancer Institute, 2025) assessed whether postoperative radiotherapy (RT) could safely be omitted in women ≥65 years old with low-risk, estrogen receptor–positive T1N0 breast cancer
METHODS:
- Prospective national multicenter cohort study
- Swedish Breast Cancer Group
- Participants
- Women ≥65 years
- Unifocal, nonlobular, grade 1 or 2, estrogen receptor–positive, T1N0 (≤2 cm and node negative) breast cancer
- Treated with breast-conserving surgery and endocrine therapy for 5 years
- Exposures
- Omission of postoperative RT
- Study design
- Patients were followed up with mammography at least annually for 10 years
- Primary outcome
- Local recurrence
- Secondary outcomes
- Contralateral breast cancer
- Recurrence-free survival
- Overall survival
RESULTS:
- 601 participants
- Median age: 71 (range, 65 to 90)
- Median tumor size: 11 (range, 3 to 20) mm
- Median follow-up: 119 (range, 103 to 121) months
- Cumulative incidence of local recurrence
- At 5 years: 1.5% (95% CI, 0.8 to 2.8)
- At 10 years: 5.5% (95% CI, 3.8 to 7.6)
- Cumulative incidence of contralateral breast cancer
- At 5 years: 1.7% (95% CI, 0.9 to 3.0)
- At 10 years: 4.5% (95% CI, 3.0 to 6.6)
- Overall survival rate at 10 years: 83.1% (95% CI, 80.8 to 85.4)
- Deaths due to breast cancer: 0.5%
CONCLUSION:
- Omitting radiation after breast-conserving surgery may be safe for women 65 or older with low-risk, ER+ breast cancer
- The authors conclude
The long-term results of this prospective cohort study add to the growing body of evidence indicating that withholding RT in a selected cohort of low-risk patients with breast cancer is safe and could be an option for patients fulfilling these criteria
Learn More – Primary Sources:
Omission of postoperative radiotherapy after breast-conserving surgery in low-risk breast cancer
Meta-Analysis: What is the Threshold for Daily Step Counts Associated with Better Health Outcomes?
BACKGROUND AND PURPOSE:
- Previous reviews of the literature have not found enough evidence to recommend a certain step count target
- Ding et al. (The Lancet Public Health, 2025) synthesized the dose-response relationship between daily steps and health outcomes including all-cause mortality, cardiovascular disease and other health outcomes
METHODS:
- Systematic review and meta-analysis
- Inclusion criteria
- Prospective studies
- Studies that examined the relationship between device-measured daily steps and health outcomes among adults
- Study design
- Risk of bias was assessed
- Hazard ratio (HR) from individual studies were synthesized with random-effects dose-response meta-analysis
- Certainty of evidence was assessed with GRADE criteria
- Primary outcomes
- Mortality
- Cardiovascular disease
- Cancer
- Type 2 diabetes
- Cognitive outcomes
- Mental health outcomes
- Physical function
- Falls
RESULTS:
- 57 studies | 35 cohorts
- Used for meta-analysis: 31 studies | 24 cohorts
- There was an inverse, non-linear dose-response association with steps and several health outcomes, with inflection points at approximately 5000 to 7000 steps/day
- All-cause mortality
- Cardiovascular disease
- Dementia
- Falls
- There was an inverse linear association between steps and the following health outcomes
- Cardiovascular disease mortality
- Cancer
- Cancer mortality
- Type 2 diabetes
- Depressive symptoms
- Compared with 2000 steps per day, 7000 steps per day was associated with lower
- All-cause mortality
- HR 0.53 (95% CI, 0.46 to 0.60) | I2=36.3
- Moderate certainty | 14 studies
- Cardiovascular disease incidence
- HR 0.75 (95% CI, 0.67 to 0.85) | I2=38.3%
- Moderate certainty | 6 studies
- Cardiovascular disease mortality
- HR 0.53 (95% CI, 0.37 to 0.77) | I2=78.2%
- Low certainty | 3 studies
- Cancer mortality
- HR 0.63 (95% CI, 0.55 to 0.72) | I2=64.5%
- Moderate certainty | 3 studies
- Type 2 diabetes
- HR 0.86 (95% CI, 0.74 to 0.99) | I2=48.5%
- Moderate certainty | 4 studies
- Dementia
- HR 0.62 (95% CI, 0.53 to 0.73) | I2=0%
- Moderate certainty | 2 studies
- Depressive symptoms
- HR 0.78 (95% CI, 0.73 to 0.83) | I2=36.2%
- Moderate certainty | 3 studies
- Falls
- HR 0.72 (95% CI, 0.65 to 0.81) | I2=47.5%
- Very low certainty | 4 studies
- All-cause mortality
CONCLUSION:
- A daily step count of 7000 steps per day is associated with significant improvements in a range of health outcomes
- 7000 daily steps may be more achievable than the often suggested 10,000 daily steps
- Limitations include lack of age-specific analyses, few studies for some outcomes, and residual confounding
- The authors state
Although risk reductions occur even at lower step counts, they continue with increasing steps per day
Approximately 7000 steps per day was associated with risk reductions for all outcomes examined and might serve as a practical quantitative public health target
Learn More – Primary Sources:
Daily steps and health outcomes in adults: a systematic review and dose-response meta-analysis
Meta-Analysis: Is a Single Dose of Fosfomycin as Effective as Other Antibiotics for the Treatment of Uncomplicated UTI?
BACKGROUND AND PURPOSE:
- Fosfomycin is a broad-spectrum antibiotic that is known to be effective against microorganisms that cause urinary tract infection (UTI) but is not commonly prescribed
- Verma et al. (Journal of Mid-Life Health, 2025) assessed the effectiveness and safety of single-dose fosfomycin vs standard antibiotics for treating UTIs in women
METHODS:
- Systematic review and meta-analysis
- Inclusion criteria
- Randomized controlled trials
- Studies that assessed the efficacy and safety of fosfomycin for uncomplicated UTI in women or ASB in pregnant women
- Study design
- Asymptomatic bacteriuria (ASB) was also studied
- Risk of bias was assessed Random and fixed effects models were used to calculate odds ratio (OR)
- Primary outcome
- Clinical resolution of uncomplicated UTI
RESULTS:
- 22 RCTs
- A single-dose of fosfomycin was comparable with other antibiotic agents in clinical resolution of uncomplicated UTI
- OR 1.11 (95% CI, 0.88 to 1.41)
- I2=0% | P=0.37 | Moderate certainty
- A single dose of fosfomycin was also comparable to other antibiotics for the microbiological resolution of
- Uncomplicated UTI
- OR 1.02 (95% CI, 0.83 to 1.25)
- I2=34% | P=0.88 | Moderate certainty
- Among pregnant women with ASB, microbiological resolution rate was similar to other antibiotics
- 5 studies | 577 participants
- OR 0.76 (95% CI, 0.45 to 1.28)
- I2=0% | P=0.30 | Moderate certainty
- Uncomplicated UTI
- Incidence of adverse events was similar for patients receiving fosfomycin or other antibiotics
- OR 0.97 (95% CI, 0.77 to 1.23)
- I2=41% | P=0.82 | Moderate certainty
CONCLUSION:
- Single-dose fosfomycin is as effective as other commonly prescribed antibiotics for uncomplicated UTI including for asymptomatic bacteriuria in pregnancy
- The authors state
In fact, prescribing a single dose of fosfomycin (3 g) as part of routine practice can promote better compliance and reduce the likelihood of antibiotic resistance
This finding highlights the importance of considering fosfomycin as a viable treatment option for uncomplicated UTIs in females
Learn More – Primary Sources:
Meta-Analysis: How Common Is Celiac Disease in First-Degree Relatives?
BACKGROUND AND PURPOSE:
- Karimzadhagh et al. (The American Journal of Gastroenterology, 2025) estimated celiac disease prevalence among first-degree relatives
METHODS:
- Systematic review and meta-analysis
- Inclusion criteria
- Observational studies
- Studies that reported rates of celiac disease, as determined using the anti-tissue transglutaminase antibody test, among first-degree relatives of someone with the disease
- Study design
- Random effects models were used
- Heterogeneity was assessed
RESULTS:
- 34 studies | 10,016 first degree relatives of individuals with celiac disease
- Pooled estimates of celiac disease prevalence among first-degree relatives
- Seroprevalence: 11% (95% CI, 9 to 13)
- Biopsy-confirmed: 7% (95% CI, 6 to 9)
- Daughters and sisters had the highest prevalence rates vs sons and brothers
- Daughters: 23% | Sons: 6%
- Sisters: 14% | Brothers: 9%
- Regions with the highest prevalence
- Seroprevalence
- Hungary: 24% | Cuba: 19%
- Biopsy-confirmed
- Serbia: 16% | USA: 15%
- Seroprevalence
- Most common GI symptoms
- Abdominal pain: 42%
- Bloating: 39%
- Flatulence: 38%
- Most common non-Gl symptom
- Pallor: 54%
- Asymptomatic first-degree relatives with confirmed celiac disease: 34%
CONCLUSION:
- The prevalence of celiac disease among first-degree relatives of someone with celiac disease was around 7%
- The rate of disease was highest among daughters and sisters
- Over one third of confirmed cases were asymptomatic
- The authors state
Routine screening for first-degree relatives, the primary high-risk group, could support early detection and effective management of CeD
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Aluminum Exposure Through Early Childhood Vaccination Is Not Associated with an Increased Risk of Autoimmune, Allergic or Neurodevelopmental Disorders
BACKGROUND AND PURPOSE:
- Aluminum based adjuvants are common in childhood vaccines (e.g. Tdap), and are used to increase the immune response to the vaccine
- Findings from animal studies have caused theoretical concern
- There is no evidence from human studies
- Andersson et al. (Annals of Internal Medicine, 2025) assessed the association between cumulative aluminum exposure from early childhood vaccination and risk for autoimmune, atopic or allergic, and neurodevelopmental disorders
METHODS:
- Population-based cohort study
- Danish national Medical Birth Registry
- Population
- Children born between 1997 and 2017
- Exposures
- Cumulative aluminum amount received (per 1-mg increase) through vaccination during the first 2 years of life
- Primary outcomes
- Incident events of 50 chronic disorders, including
- Autoimmune: Dermatologic | Endocrinologic | Hematologic | Gastrointestinal | Rheumatic
- Atopic or allergic: Asthma | Atopic dermatitis | Rhinoconjunctivitis | Allergy
- Neurodevelopmental: Autism spectrum disorder | Attention deficit–hyperactivity disorder
- Incident events of 50 chronic disorders, including
RESULTS:
- 1,224,176 children born in Denmark
- Cumulative aluminum exposure from vaccination during the first 2 years of life was not associated with increased rates of any of the 50 disorders assessed
- For any autoimmune disorder
- Adjusted hazard ratio (aHR) per 1 mg increase in aluminum exposure 0.98 (95% CI, 0.94 to 1.02)
- For any atopic or allergic disorder
- aHR per 1 mg increase in aluminum exposure 0.99 (95% CI, 0.98 to 1.01)
- For any neurodevelopmental disorder
- aHR per 1 mg increase in aluminum exposure 0.93 (95% CI, 0.90 to 0.97)
- For any autoimmune disorder
- For most of the outcomes analyzed individually, the upper bounds of the 95% CIs precluded relative increases greater than 10% or 30%
- None of the assessed outcomes had a 95% CI with a lower bound greater than 1.00
CONCLUSION:
- The results of this large population-based study of cumulative aluminum exposure due to early childhood vaccination are most compatible with no increase in risk with exposure
- However, the authors note that a small relative risk increase cannot be statistically excluded, especially for rarer outcomes
- The authors state
Our study, based on a nationwide cohort of about 1.2 million children with analyses across a 24-year period, offers a large-scale, population-based evaluation of the safety of aluminum-adsorbed vaccines in childhood vaccination programs
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Aluminum-Adsorbed Vaccines and Chronic Diseases in Childhood: A Nationwide Cohort Study
Perioperative Management of GLP-1 Receptor Agonists (GLP-1RAs)
SUMMARY
GLP-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes, obesity, and heart failure. Their ability to delay gastric emptying raises perioperative risks, notably aspiration during anesthesia, even after standard fasting. Post-operative complications can mimic the nausea, abdominal pain, vomiting and constipation side effects from GLP-1RAs, making complications difficult to assess. Multi-society guidance recommends a risk-based, multidisciplinary approach to perioperative management.
Key Considerations
- GLP-1RAs slow gastric emptying, increasing aspiration risk during sedation or anesthesia.
- Symptoms e.g., nausea | vomiting | abdominal pain| constipation may overlap with perioperative complications
- Evidence-based perioperative guidelines are limited; clinical practice recommendations are consensus-driven
Risk Assessment:
These variables can increase the risk of delayed gastric emptying, aspiration. Assess risk factors well before surgery to allow for preoperative planning.
- Escalation phase: Higher risk of delayed gastric emptying than maintenance phase
- High dose: Greater GI side effects and risk
- Weekly dosing: More GI side effects than daily formulations
- Active GI symptoms: Nausea, vomiting, abdominal pain, dyspepsia, constipation
- Comorbid conditions e.g., Gastroparesis | bowel dysmotility | Parkinson’s disease
Perioperative Management
Shared Decision-Making
- Involve patient, proceduralist, anesthesiologist, and prescribing provider
- Weigh metabolic benefits of GLP-1RA vs. aspiration risk
- Avoid bias: Do not withhold solely for obesity indication
Holding GLP-1RA Therapy
- No elevated risk: Continue GLP-1RA
- Elevated risk: Consider withholding GLP-1RA
- Daily formulations: Hold on day of surgery
- Weekly formulations: Hold 1 week prior
- Bridging therapy: May be resource-intensive and not always feasible
- All patients: Assess for delayed gastric emptying symptoms on day of procedure
Aspiration Risk Reduction
- Preoperative diet modification: Consider 24-hour liquid diet for at-risk patients
- Gastric ultrasound: Use if concern for retained gastric contents (institution-dependent)
- Anesthesia planning: Consider rapid sequence induction for intubation if aspiration risk is high
- Shared decision-making: Discuss risks/benefits of proceeding vs. canceling procedure if retained gastric contents are present
Special Populations
- Obesity/overweight: Do not withhold GLP-1RA solely for these indications
- Other gastroparesis patients: Apply similar perioperative precautions.
Conclusion
- Perioperative GLP-1RA management should be individualized, emphasizing shared decision-making and risk assessment
- Recommendations may change as new therapies and evidence emerge
- Current guidance is based on expert consensus, not high-level evidence
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Secondary Stroke Prevention
SUMMARY:
Each year, roughly one million Americans experience a stroke or transient ischemic attack (TIA). Nearly 25% of strokes each year are recurrent, occurring in patients who have already experienced a prior stroke. Patients who have suffered one stroke are more at risk of suffering another, and so preventing secondary strokes is a cornerstone of post-stroke care. Repeated strokes can lead to increased risk of dementia, disability, and increased mortality. The American Heart Association/American Stroke Association have put together a guideline with recommendations for the prevention of secondary stroke.
Diagnostic Evaluation
- For patients who present with stroke or TIA, diagnostic evaluation should include
- EKG, to screen for arrhythmia or cardiomyopathy
- CT +/- MRI brain
- Bloodwork: CBC | PT/INR | Glucose | A1c | Lipid panel | Creatinine
- In cases of symptomatic anterior circulation cerebral infarct, carotid arteries should be evaluated for revascularization targets
- CTA | MRA | Carotid US
- In patients with cryptogenic stroke work up also includes
- Cardiac echocardiography
- Cardiac CT/MRI in some cases (e.g., Embolic stroke unknown source)
- Long-term rhythm monitoring (e.g., Implantable loop recorder | Holter monitor) IF patient has no contraindication to anticoagulation
- In the appropriate clinical context, consider obtaining further testing (e.g., Hypercoagulable testing | Lumbar puncture | Infectious studies | Drug use screen | Systemic inflammatory markers)
- CTA | MRA
- In patients with stroke or TIA and negative initial brain imaging, follow up CT or MRI may be obtained to confirm diagnosis
- For patients with ischemic stroke, diagnostic work up should be done soon after stroke is diagnosed, ideally completed with 48 hours of stroke symptoms
Stroke Subtypes
Hemorrhagic Stroke
- Intracerebral hemorrhage
- Subarachnoid hemorrhage
Ischemic Stroke
- Lacunar stroke
- Most, but not all, lacunar strokes are due to small vessel disease
- Cardioembolic
- Left atrial thrombus | Left ventricular thrombus
- Atrial fibrillation | Atrial flutter
- Cardiomyopathy
- Valvular disease (e.g., Bioprosthetic/mechanical heart valve | Rheumatic valve disease)
- Endocarditis
- Atrial Myxoma
- Cryptogenic
- Embolic stroke unknown source (ESUS): Diagnosed when no source of stroke is found despite extensive work up (e.g., Arterial imaging | Echocardiography | Extended rhythm monitoring | Lipid panel | A1c)
- Non-ESUS: A stroke of unclear origin that does not appear to have been embolic
- Large Artery
- Carotid artery disease
- Extracranial vertebral artery stenosis
- Arterial dissection
Modifiable Risk Factors
- Management of vascular risk factors is critically important for reduction of secondary stroke risk
- The vast majority (up to 90%) of strokes can be prevented by focusing on risk factor modification
- Addressing multiple risk factors has additive benefits for stroke risk reduction
- Vascular risk factors include
- Diabetes: Goal A1c ≤ 7% for most patients | GLP-1 and SGLT2-inhibitors preferred agents depending on co-morbid conditions (See “Related Topics” below for more information)
- Hypertension: Thiazides and ARB/ACE-I specifically recommended for blood pressure control and reducing stroke risk | Goal BP <130/80
- Hyperlipidemia: High intensity statin (e.g., Atorvastatin 80mg daily) | Add therapy as needed for high-risk patients or those with persistent LDL ≥70 mg/dL (e.g., Ezetimibe | PCSK-9 inhibitor)
- Hypertriglyceridemia: Icosapent Ethyl 2g twice daily for select patients
- Tobacco use: Smoking cessation | Avoidance of environmental tobacco smoke
- Lifestyle changes, with the assistance of a multidisciplinary team, should also be implemented to decrease modifiable risks including
- Healthy diet: Low salt (e.g., Reduction of salt intake to 1.5g/day) | Mediterranean diet
- Physical activity: Moderate intensity aerobic activity for ≥10 minutes four times a week | Vigorous intensity aerobic activity for ≥20 minutes two times a week | Break up sedentary time with short standing or light exercise intervals every 30 minutes
- Reduce or eliminate alcohol consumption
- Avoid illicit drug use (e.g., Stimulants | IV drug use)
- Treatment and screening for obstructive sleep apnea
Anti-Thrombotic and Invasive Therapy
- Antithrombotic therapy, including antiplatelet or anticoagulant agents, is recommended for nearly all patients following ischemic stroke
- Contraindications to anticoagulation include: High risk of bleeding | Large infarctions | Continued hemorrhagic conversion | Uncontrolled elevated blood pressure
- In patients with non-cardioembolic ischemic TIA or stroke, antiplatelet therapy is preferred over oral anticoagulation to minimize risk of bleeding
- ASA (50 to 325mg daily) should be started in all ischemic non-cardioembolic stroke and TIA patients
- Clopidogrel (Plavix) should be added for dual antiplatelet therapy (DAPT) in cases of high-risk TIA or minor stroke (NIHSS ≤3) (defined as an ABCD2 score of ≥4) and continued for 21 to 90 days
- Ticagrelor (Brilinta) can be considered in place of Clopidogrel (Plavix) for a 30-day course in patients with: Minor to moderate stroke (NIHSS ≤5) | High risk TIA (ABCD2 score ≥6) | Symptomatic intra/extra-cranial stenosis ≥30% in an artery which may have caused the event
Cardioembolic stroke
- In patients with TIA or stroke AND nonvalvular atrial fibrillation or atrial flutter, oral anticoagulation (e.g., Apixaban (Eliquis) | Rivaroxaban (Xarelto) | Warfarin (Coumadin) is recommended to reduce risk of recurrent stroke
- This recommendation is regardless of if the atrial fibrillation is permanent, persistent, or paroxysmal
- In the absence of a moderate – severe mitral stenosis or a mechanical heart valve, a direct oral anticoagulation e.g., Apixaban (Eliquis) | Rivaroxaban (Xarelto) | Dabigatran (Pradaxa) | Edoxaban (Lixiana) is recommended over Warfarin (Coumadin)
- Anticoagulation post stroke should begin within 2 to 14 days of the initial event, though patients with TIA and atrial fibrillation/flutter may start anticoagulation immediately
- Patients at high risk of hemorrhagic conversion may delay starting anticoagulation for at least 14 days post stroke
- Apixiban and Warfarin are preferred for ESRD patients
- Direct oral anticoagulants (DOACs) are recommended over warfarin for cancer patients with Atrial fib/flutter and TIA or stroke
- Warfarin is preferred for patients with valvular atrial fibrillation/flutter
- Patients with endocarditis and TIA or stroke should undergo surgery for removal of vegetations if they have: Recurrent emboli AND persistent vegetations despite antibiotic therapy | Mobile vegetations >10mm | Other indications for valve surgery
- In stroke patients with LV thrombus, anticoagulation with therapeutic warfarin is recommended for at least 3 months
- Warfarin for 3 months is additionally recommended if the patient has left atrial thrombus in the setting of cardiomyopathy
- Determining which cardioembolic stroke patients with a patent foramen ovale (PFO) would benefit from PFO closure is a complicated process that should involve neurologists and cardiologists
Large artery stroke
- In patients with stroke or TIA caused by 50 to 90% stenosis of a major intracranial artery, ASA 325mg/d is recommended to reduce risk of recurrent stroke and vascular death
- For patients with recent stroke (within the last 30 days) and severe stenosis (70 to 99%) providers can add Clopidogrel (Plavix) 75mg/d to ASA 325mg/d for 90 days to further reduce risk
- In patients within 24 hours of a minor stroke OR high-risk TIA with concomitant ipsilateral stenosis (>30%) of a major intracranial artery, the addition of Ticagrelor (Brilinta) 90mg twice daily to ASA 325mg/d for 30 days can be considered
- In patients with 50 to 99% stenosis of a major intracranial artery, the addition of Cilostazol 200mg/d in addition to ASA or Clopidogrel can be considered
- Angioplasty and stenting of stenosis of major intracranial arteries is generally not recommended
- In patients with TIA or non-disabling stroke within the past 6 months, and ipsilateral severe (70 to 90%) stenosis of the carotid artery, carotid endarterectomy (CEA) is recommended for patients with low (<6%) surgical risk
- This is in addition to risk factor modification and antiplatelet therapy
- CEA is also recommended in patients with more moderate stenosis (50 to 69%)
- Surgery should be performed within 2 weeks of the index event
- Carotid artery stent (CAS) may be considered for patients at higher surgical risk
Cryptogenic
- In patients with ESUS, initiating anticoagulation is not recommended
- Patients with cryptogenic stroke are otherwise treated with antiplatelet therapy as outlined above for non-cardioembolic ischemic stroke or TIA
Special populations
- Sickle cell anemia
- Patients with sickle cell anemia and prior ischemic stroke or TIA should receive chronic blood transfusions to reduce Hgb S to <30% of total hemoglobin
- Caution is advised when considering antithrombotics for secondary stroke prevention in patients with SCD because the stroke mechanism is less certain and patients with SCD are also at higher risk for hemorrhagic stroke. If there is evidence for other stroke mechanisms in a patient with SCD (ie, atherosclerosis), then reasonable to administer antithrombotics
- If unable to access blood transfusions, Hydroxyurea may be used to lower stroke risk
- Autoimmune vasculitis
- In patients with autoimmune vasculitis (e.g., Giant cell arteritis | Primary CNS angiitis) and stroke, high dose steroids should be started immediately to reduce future risk of stroke
- Infectious vasculitis
- Patients with ischemic stroke or TIA with infectious vasculitis (e.g., Varicella cerebral vasculitis | Neurosyphilis | Bacterial meningitis) should have treatment focused on treating the underlying infection
- APLS, Moya Moya
Health Equity
- As we continue to study about healthcare disparities, many guidelines have been updated to include a focus on health equity when considering treatment and management of a patient’s medical problems
- For patients following stroke and TIA, evaluating and addressing social determinants of health is recommended
- This includes: Literacy level | Language proficiency | Medication affordability | Access to housing | Food insecurity | Transportation barriers
KEY POINTS:
- Patients who have suffered a stroke or TIA are at increased risk of repeat stroke and vascular death
- The vast majority of secondary strokes can be prevented by focusing management on vascular risk factors and lifestyle modifications
- The main contributors to secondary stroke risk are abdominal obesity, hypertension, diet, tobacco use, and physical inactivity
- Antithrombotic, either antiplatelet or anticoagulation, therapy is recommended for nearly all post-stroke patients absent any contraindications
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Cardiovascular-Kidney-Metabolic (CKM) Syndrome Overview
Cardiovascular-Kidney-Metabolic (CKM) Syndrome
Cardiovascular-Kidney-Metabolic (CKM) syndrome is a systemic disorder characterized by the interconnected pathophysiology of obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). It encompasses individuals at risk for CVD as well as those with existing CVD. Due to the heavy burden of poor cardiovascular-kidney-metabolic health in the population, the American Heart Association created a presidential advisory discussing current knowledge and future needs.
CKM Syndrome Definition and Staging
“Cardiovascular-kidney-metabolic (CKM) syndrome is defined as a health disorder attributable to connections among obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD), including heart failure, atrial fibrillation, coronary heart disease, stroke, and peripheral artery disease. CKM syndrome includes those at risk for CVD and those with existing CVD”
A staging system for CKM syndrome has been proposed to guide prevention and treatment:
- Stage 0: No CKM risk factors
- Stage 1: Excess or dysfunctional adiposity (e.g., obesity)
- Stage 2: Presence of metabolic risk factors like Hypertension | Diabetes | Hypertriglyceridemia| Metabolic syndrome| moderate-to-high risk CKD
- Stage 3: Subclinical CVD or risk equivalents (high predicted CVD risk or very high-risk CKD)
- Stage 4: Clinical CVD in CKM syndrome
Risk-enhancing factors influence progression through these stages, emphasizing the importance of early identification and intervention
Screening and Risk Prediction
- Screening for CKM risk factors should occur across the lifespan, with frequency and intensity tailored to the CKM stage
- New risk prediction tools i.e., AHA PREVENT Calculator (See ‘Learn More’ below) incorporate assessments starting at age 30, evaluating risks for both atherosclerotic CVD and heart failure, facilitating earlier and more precise risk stratification
Clinical Management and Therapeutic Strategies
- Lifestyle Modification: Addressing excess or dysfunctional adiposity through weight loss and behavioral changes is fundamental to preventing progression and enabling regression of CKM stages
- Pharmacotherapy: Use of cardioprotective antihyperglycemic agents is prioritized based on patient profile:
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors are favored for patients with CKD, heart failure, or high heart failure risk.
- Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are recommended for those with uncontrolled hyperglycemia (HbA1c ≥9 %) | high insulin requirements | severe obesity (BMI ≥35 kg/m²).
- Combined use of SGLT2 inhibitors and GLP-1RAs may be considered for patients with multiple CKM risk factors and high CVD risk.
Kidney Function Monitoring
- Measurement of urine albumin-creatinine ratio and eGFR or cystatin-C is essential in patients with CKD | Diabetes | Hypertension | Metabolic syndrome to characterize risk and guide kidney-protective therapies e.g., ACE-Inh | ARBs | SGLT2 inhibitors | finerenone
Social Determinants of Health (SDOH)
- Given the disproportionate burden of CKM syndrome among populations with adverse SDOH, systematic screening for these factors is recommended.
- Community partnerships to promote cardiovascular health equity
KEY POINTS:
- CKM syndrome represents a critical public health challenge marked by the interplay of metabolic, kidney, and cardiovascular disorders.
- Early identification through staging and risk assessment, combined with targeted lifestyle and pharmacologic interventions, offers the potential to improve outcomes and reduce cardiovascular morbidity and mortality.
- Addressing social determinants and adopting integrated care approaches are essential to advancing CKM health on a population level
- Advisory highlights the need for integrated and interdisciplinary care models | enhanced education on CKM health and investment in research | improved access to obesity lifestyle and pharmacotherapy treatments
Learn More-Primary Sources
Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association
