2 Minute Medicine Rewind September 7, 2026
Maternal Body Mass Index, Gestational Weight Gain, and Cardiovascular Disease in Offspring
1. Higher maternal body mass index (BMI) was associated with an increased risk of cardiovascular disease in offspring, with stronger relationships seen with increasing BMI.
Evidence Rating Level: 2 (Good)
CVD, the leading cause of mortality worldwide, has had increasing prevalence in younger populations. Therefore, it is essential to understand the risk factors for early CVD. It is known that maternal obesity and excessive gestational weight gain (GWG) during pregnancy are associated with suboptimal intrauterine environments and adverse birth outcomes. However, few studies have studied the relationship between excessive GWG and long-term CVD risk in the offspring. This nationwide cohort study uses the Swedish Medical Birth Register, which contains antenatal, obstetric, and neonatal care for 98%-99% of births in Sweden. Excluding 51 526 offspring diagnosed with congenital heart disease, this study included 2 496 335 offspring from 1982-2014. 1 212 687 (48.6%) were female and 1 283 648 (51.4%) were male. CVD was defined as a composite measure of vascular disease (ischemic heart disease and cerebrovascular disease), heart failure, hypertensive disease, cardiomyopathy, and atrial fibrillation. At the end of follow-up, the mean (SD) age was 23.3 (9.8) years. 22 510 offspring (0.9%) were diagnosed with CVD; 17 605 (0.7%) died, and 55 068 (2.2%) emigrated before CVD. Compared with offspring of mothers with normal BMI, the HRs for major CVD were 1.29 (95% CI, 1.24-1.33) for maternal overweight, 1.66 (95% CI, 1.57-1.75) for maternal obesity class 1, 2.16 (95% CI, 1.96-2.39) for maternal obesity class 2, and 2.74 (95% CI, 2.29-3.28) for maternal obesity class 3. Furthermore, offspring of mothers with obesity were at significantly greater risk of heart failure, hypertensive disease, cardiomyopathy, and atrial fibrillation, with risk increasing with BMI. Further research should characterize the pathophysiological mechanism of how obesogenic environments increase the risk of CVD.
1. Long-term exposure to particulate matter with diameter ≤2.5 μm (PM2.5) was significantly associated with elevated cardiovascular (CVD) risk, with Cl−, BC, or SO42− having particularly hazardous profiles.
Evidence Rating Level: 2 (Good)
PM2.5 exposure is a known independent risk factor for CVD. However, it is not only PM2.5 mass concentration that worsens health outcomes. Certain chemical components of PM2.5 have been found to have varying levels of oxidative stress and cytotoxicity. This study sought to investigate the associations between CVD and long-term exposure to PM2.5 components, considering both absolute and relative concentrations. The authors utilized data from the China Kadoorie Biobank (CKB) cohort, which recruited 512 724 participants aged 30 to 79 years from 2004-2008. After excluding patients with heart disease, stroke, or cancer at baseline, 487 037 patients (mean [SD] age, 51.5 [10.5] years; 59.1% female) were included in the final analysis. The daily mean concentrations of PM2.5 and its 6 key chemical components (organic matter (OM), black carbon (BC), Cl−, NO3−, SO42−, and NH4+) were obtained from the ChinaHighAirPollutants (CHAP) data sets. Individuals who moved out of their baseline cities were considered lost to follow-up, with a proportion of <1%. The average composition of PM2.5 was 38.8% OM, 19.8% SO42−, 17.6% NO3−, 12.0% NH4+, 7.9% BC, and 3.9% Cl−. Those exposed to median or higher levels of PM2.5 were more likely to live in rural areas. After stratifying by PM2.5 levels, the HRs for total CVD per IQR increase were 1.15 (95% CI: 1.13-1.17) for BC, 1.17 (95% CI: 1.15-1.18) for OM, 1.28 (95% CI: 1.25-1.32) for Cl−, 1.29 (95% CI: 1.24-1.33) for NO3−, and 1.23 (95% CI: 1.20-1.25) for SO42−. Increasing quartiles were also significantly associated with higher rates of ischemic heart disease and ischemic stroke, but only BC, Cl−, NO3−, and SO42− were significantly associated with higher rates of hemorrhagic stroke. Increasing the relative proportions of Cl−, BC, and SO42− was associated with higher CVD risk, while increasing the relative proportions of NO3− and OM were associated with a reduced risk for ischemic heart disease and stroke.
Oral Anticoagulants in Patients With Atrial Fibrillation and Advanced CKD Not Requiring Dialysis
1. In patients with atrial fibrillation and advanced chronic kidney disease (CKD) not receiving dialysis, apixaban was associated with significantly lower rates of bleeding and ischemic stroke compared to warfarin.
Evidence Rating Level: 2 (Good)
CKD is associated with an increased burden of cardiovascular complications, with studies showing a 12%-18% of AF in patients with CKD. Direct oral anticoagulants (DOACs) and warfarin are commonly used to prevent cardioembolic events in these patients. However, many of the initial pivotal trials excluded patients with CKD stage 4 or 5. Thus, it remains unclear how effective DOACs and warfarin are in this subgroup. This cohort study used patient data from 2 large United States health insurance claims databases and included patients with a diagnosis of CKD stage 4 or 5, a diagnosis of AF, CHA2DS2-VASc score of 2 or greater for men or 3 or greater for women, and have never required dialysis. 42,052 patients were identified, with 14 712 being new users of apixaban (mean [SD] age, 78.33 [7.26] years; 54.1% female), 6335 being new users of warfarin (mean [SD] age, 78.12 [7.05] years; 49.7% female), and 21 005 patients with no OAC use (mean [SD] age, 78.05 [7.49] years; 51.4% female). Compared with nonuse, apixaban was associated with a significantly higher rate of major bleeding (63.8 vs 47.5 per 1000 person-years (PY); HR, 1.32 [95% CI, 1.11 to 1.58]; RD, 17.16 [95% CI, 2.45 to 31.87] per 1000 PYs) and a significantly lower rate of ischemic stroke (9.4 vs 22.3 per 1000 PYs; HR, 0.46 [95% CI, 0.32 to 0.66]; RD, −12.67 [95% CI, −20.65 to −4.69] per 1000 PYs). Compared to nonuse, warfarin was associated with a significantly higher rate of major bleeding (116.2 vs 47.5 per 1000 PYs; HR, 2.44 [95% CI, 2.06 to 2.88]; RD, 70.20 [95% CI, 51.94 to 88.47] per 1000 PYs) and a nonsignificant decrease in rate of ischemic stroke (20.3 vs 22.3 per 1000 PYs; HR, 0.87 [95% CI, 0.61 to 1.22]; RD, −2.31 [−11.44 to 6.81] per 1000 PYs). Compared to warfarin, apixaban was associated with both a lower rate of major bleeding (HR, 0.55 [95% CI, 0.46 to 0.65]; RD, −53.30 [95% CI, −72.47 to −34.12] per 1000 PYs) and a lower rate of ischemic stroke (HR, 0.50 [95% CI, 0.33 to 0.78]; RD, −10.48 [95% CI, −18.37 to −2.59] per 1000 PYs). Both apixaban 5 mg twice daily and apixaban 2.5 mg twice daily were associated with lower rates of bleeding (standard dose: HR, 0.58 [95% CI, 0.45 to 0.75]; reduced dose: HR, 0.61 [95% CI, 0.50 to 0.75]) and ischemic stroke (standard dose: HR, 0.54 [95% CI, 0.30 to 0.98]; reduced dose: HR, 0.51 [95% CI, 0.31 to 0.84]) compared to warfarin.
1. Cataract surgery in patients with diabetes is associated with a significantly increased incidence of diabetic retinopathy (DR).
Evidence Rating Level: 2 (Good)
DR is a significant cause of blindness among adults and is highly prevalent among patients with diabetes worldwide. Alongside DR, cataracts are another ophthalmologic pathology frequently seen in this patient population. However, the association between cataract surgery and the risk of developing DR and progression of existing DR remain controversial. This retrospective cohort study therefore sought to investigate the association between cataract surgery and the development and progression of DR. 31,206 patients from Taiwan with a history of diabetes and cataracts between 2010 and 2021 were included in the study. Patients who underwent cataract surgery were further matched in two stages, with a 1:2 matching based on age and sex and 1:1 propensity score matching. Among patients who underwent cataract surgery, the progression rate of DR was approximately 2% and 3% at 6 months and 1 year, respectively, compared to approximately 0.5% and 1% at 6 months and 1 year in the comparison group (p < 0.05). Patients who underwent cataract surgery also had a significantly increased incidence of DR within 1 year compared to the comparison group, (adjusted odds ratio, 3.40 [95% CI, 2.65-4.36] and 3.03 [95% CI, 2.26-4.06] for the 1:2 age- and sex matched and 1:1 propensity score-matched groups, p < 0.001). Overall, this study found that among patients with diabetes who underwent cataract surgery, the risk of DR incidence and progression was increased compared to those who did not undergo cataract surgery.
1. The use of molecularly guided therapy (MGT) was associated with significantly improved progression-free survival (PFS) compared with standard platinum-based chemotherapy in patients with unfavourable cancer of unknown primary (CUP).
Evidence Rating Level: 1 (Excellent)
Comprehensive genetic profiling (CGP) is a novel approach that allows for detection of distinct genomic alterations, allowing for personalized MGT. CUP represents a heterogeneous group of malignancies which have had little progress in improving outcomes, and within which there is a high level of genomic alterations. The CUPISCO trial was a phase II randomized trial to investigate MGT compared with standard platinum-based chemotherapy in patients with a new diagnosis of unfavourable, nonsquamous CUP. The primary analysis was previously completed with a clinical cutoff in 2023, and analysis with extended follow-up was completed to verify these results. 438 patients between July 2018 and December 2022 from 159 centres in 34 countries with a new diagnosis of non-squamous CUP with no previous systemic therapy exposure reached disease control after induction and were randomized to MGT or standard platinum-based chemotherapy. Median follow-up time was 37.0 months (range, 0.0-67.8 months). The updated median PFS was 6.1 months (95% CI, 4.7-6.5) in the MGT arm compared with 4.4 months (95% CI, 4.2-6.4) in the control arm. Among patients who had actionable molecular profiles, the median PFS was 8.2 months (95% CI, 5.0-9.3) in the MGT arm and 5.5 months (95% CI, 4.0-6.9) in the control arm. Overall, analysis of the extended follow-up of the CUPISCO trial aligned with the primary analysis, demonstrating that the use of CGP and subsequent MGT in patients with new non-squamous CUP was associated with significantly improved PFS compared with standard platinum-based chemotherapy.
Image: PD
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