In comparison to using a contemporary cardiac troponin I (cTn) assay with a common diagnostic threshold for women and men, implementation of a high-sensitivity (hs-cTn) assay with sex-specific thresholds increased by 42% the number of female patients identified as having myocardial injury—nonischemic myocardial injury or type 1 or type 2 myocardial infarction (MI). This was five times higher than the increase in the number of men diagnosed. However, this better recognition did not translate into improved treatments or outcomes for female patients (J Am Coll Cardiol 2019;74:2032-43).
Using hs-cTn I 99th percentile diagnostic thresholds of 16 ng/L for women and 34 ng/L in men in a population of 47,037 patients being evaluated for suspected acute coronary syndrome increased across-the-board recognition of myocardial injury. The diagnosis of type 1 MI, type 2 MI, and nonischemic myocardial injury all rose in both women and men, and in all cases the increase was greater in women (25% versus 6%, 39% versus 9%, and 67% versus 12%, respectively).
Even with this improved diagnosis, however, women with myocardial injury were about half as likely as men to receive recommended interventions, including coronary angiography (26% versus 46%), coronary revascularization (15% versus 34%), and dual antiplatelet therapy (26% versus 43%). Use of the hs-cTn assay with sex-specific diagnostic thresholds also was not associated with substantive improvements in the primary outcomes of recurrent MI or cardiovascular death after 1 year in either women or men.
These findings underscore that more robust tests alone will not carry the day for better cardiovascular care for women, according to both the researchers and editorialists who commented on the study. “It is clear from this study that simply improving diagnostic accuracy cannot remedy deeply embedded gender disparities in attitudes, practice, and outcomes,” wrote editorialists Allan Jaffe, MD, and Sharonne Hayes, MD. “Simply put, if one does not act on the data, no diagnostic test will ever have additional worth” (J Am Coll Cardiol 2019;74:2044-6).
Artificial Pancreas System Outperforms Current Glucose Management Technology
A novel closed-loop insulin delivery and glucose monitoring system (also known as an artificial pancreas) enabled patients to meet glycemic control targets more effectively than current technology (N Engl J Med 2019; doi:10.1056/NEJMoa1907863).
Patients randomly assigned to the new system as part of a 6-month trial of 168 individuals with type 1 diabetes stayed 2.6 hours per day longer in the target glucose range of 70 to 180 mg/dL compared with participants who used a sensor-augmented pump and a continuous glucose monitor.
The 112 individuals using the closed-loop system also experienced 13 minutes less time each day in hypoglycemia. In addition, their HbA1c levels improved, to a median of 7.06±0.79 during the trial period versus 7.40±0.96 during a baseline period while they were learning to use the system and researchers were collecting data. In contrast, individuals using the sensor-augmented pump had a median HbA1c level during the baseline period of 7.40±0.76 versus 7.39±0.92 during the trial period.
Participants using the closed-loop system reported 17 adverse events compared with two among sensor-augmented pump users. Most of the events involving the closed-loop system were caused by infusion set failures, according to the investigators.
DTC Genetic Tests Likely to Yield False Negative Results for MUTYH, BRCA 1/2
In comparison to clinical-grade genetic testing, direct-to-consumer (DTC) genetic tests that analyze only a limited set of variants yield significant numbers of false-negative results, misclassifying up to 100% of results for individuals of some ethnicities, according to an abstract presented at the American Society of Human Genetics 2019 Annual Meeting (Esplin ED et al. Program number 235).
These findings highlight the value of clinical genetic testing versus the imperfections of DTC genetic tests, according to the study’s first author, Edward Esplin, MD, a clinical geneticist at Invitae, a medical genetics testing company. “The results from this type of DTC genetic screening may not be wrong but they are woefully incomplete,” he said in a prepared statement. “We hope our research underscores the need for consumers to understand the deep limitations of these health reports and seek out appropriate clinical genetic testing when trying to understand their risk of health conditions like cancer.”
Esplin and his colleagues analyzed de-identified data from two indication-based cohorts of patients referred by healthcare providers for genetic testing: 270,806 tested for MUTYH, and 119,328 for BRCA 1/2. DTC screening tests report on three BRCA 1/2 tests common in people of Ashkenazi Jewish heritage and two MUTYH variants prevalent in those of Northern European ancestry.
In the indication-based testing groups, 5,929 patients had pathogenic or likely pathogenic (P/LP) MUTYH variants, suggesting they had elevated risk for colorectal cancer. DTC testing involving just the two MUTYH variants would have missed 40% of patients who actually had homozygous or compound heterozygous MUTYH, along with 22% of MUTYH carriers. The DTC screening also would have returned false-negative results for 100% of Asian patients and 75% of African Americans.
Indication-based testing identified 4,733 individuals with P/LP BRCA 1/2 variants. Overall, 12% of this population had one of the three BRCA 1/2 variants in question, including 81% of those of Ashkenazi Jewish heritage but just 6% of other ethnicities. False negative rates for BRCA 1/2 with the DTC screening test would have ranged from 99% among African Americans to 94% in Caucasians.