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Sex-Specific hs-cTn Thresholds Could Lead to More MI Diagnoses in Women

Sex-specific thresholds used with a high-sensitivity cardiac troponin I (hs-cTn) assay could double the diagnosis of myocardial infarction (MI) in women, putting the percentage of women diagnosed with MI on par with that of men, new research indicates (BMJ 2015;350:g7873I doi:101036/bmj.g7873). The study also showed “major sex differences” in the management of MI, with less than half of women with an adjudicated MI diagnosis receiving optimal treatment, compared with most men.

The study involved 1,126 consecutive patients presenting with suspected acute coronary syndrome (ACS). Patients had troponin measurements taken at baseline and 6 or 12 hours after symptom onset with both a contemporary sensitivity assay (cTn) and hs-cTn. The limit of detection for cTn is 10 ng/L, and the upper limit for a normal reference population is 28 ng/L. In contrast, the hs-cTn assay has a limit of detection of 1.2 ng/L and an upper limit for a normal reference population of 26 ng/L. cTn has a coefficient of variation <10% at 50 ng/L, whereas hs-cTn has a coefficient of variation <10% at 6 ng/L.

Actual patient care was based solely on cTn results; researchers used hs-cTn in an independent review by two cardiologists, who considered all clinical information to classify patients as having type 1 MI, type 2 MI, myocardial injury, or unstable angina. These researchers also classified or reclassified patients using hs-cTn results with both a generic threshold (26 ng/L) and sex-specific thresholds of 34 ng/L for men and 16 ng/L for women.

Women with ACS were slightly older on average than men with ACS and had similar cardiovascular risk factors but had higher mortality risk and were less likely to have already undergone coronary revascularization.

With cTn results and a 50 ng/L threshold, 11% of women and 19% of men were classified with type 1 MI. However, with hs-cTn and a generic 26 ng/L threshold, 16% of women and 23% of men were classified with type 1 MI. When researchers used sex-specific hs-cTn thresholds, 22% of women versus 21% of men were classified as having a type 1 MI. Use of hs-cTn and an age-specific threshold also resulted in a small but significant increase in the number of women diagnosed with type 2 MI or myocardial injury.

The researchers also found that women diagnosed with MI were less likely than men to be referred to a cardiologist (80% versus 95%), receive coronary angiography (47% versus 74%), undergo coronary revascularization (29% versus 64%), or be prescribed statins at discharge (60% versus 85%). These inequalities were most pronounced in women diagnosed with MI only using hs-cTn.

While prior research also has noted sex-related differences in MI diagnosis, this difference in the past has been attributed to differences in the symptoms women and men present with. However, the authors found equal proportions of women and men exhibiting chest pain and electrocardiographic changes.

New Method Described to Detect ß cell Death

Researchers reported a novel method for assessing β cell death in individuals at risk for type 1 diabetes who subsequently developed the disease (J Clin Invest 2015; doi:10.1172/JCI78142). The method, a blood test that measures unmethylated insulin DNA, can be used as a marker for β cell death, according to the authors.

The researchers developed the method as a way to measure β cell death directly in type 1 diabetes, which up until now has been assessed indirectly by measuring autoantibodies and glucose tolerance. However, autoantibodies don’t correspond exactly with β cell death and don’t provide information about the pace of disease progression, according to the authors.

This led the investigators to pioneer a method to measure the amount of β cell-derived insulin DNA in circulation. Insulin DNA is methylated in most cell types, and the only significant source of unmethylated insulin DNA is β cells, according to the authors. The new method involves droplet digital PCR.

In an observational study of 50 participants from two cohorts at risk of developing type 1 diabetes, the authors found that those who progressed to type 1 diabetes had modestly elevated average levels of unmethylated insulin DNA in comparison to healthy control subjects. These increases in unmethylated insulin DNA were associated with decreased insulin secretion, suggesting that unmethylated insulin DNA is a marker of β cell death.

Genetic Testing Before Lung Cancer Treatment Optimizes Outcomes 

An economic analysis found that waiting for genetic testing results before starting treatment for non-small cell lung cancer (NSCLC) optimizes outcomes, and that multiplexed screening for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements with test-guided chemotherapy is cost-effective in comparison to both empiric therapy and empiric switch therapy (J Thorac Oncol 2015; doi: 10.1097/JTO.0000000000000474).

The investigators used a microsimulation model to compare life expectancy and costs of multiplexed EGFR and ALK testing with: guided chemotherapy versus empiric chemotherapy with no testing; initial empiric chemotherapy switched to targeted therapy based on molecular test results; or a total course of empiric chemotherapy followed by targeted therapy as indicated.

EGFR mutations and ALK rearrangements occur in approximately 9.5% and 3.9% of all NSCLC, respectively. Guidelines recommend testing for EGFR and ALK to guide first-line chemotherapy, but uptake of this recommendation appears underutilized in clinical care, according to the authors. At the same time, recent evidence has questioned the cost-effectiveness of this screening.

The authors found that the incremental cost-effectiveness ratio for testing and waiting for results compared to empiric chemotherapy was $136,000 per quality-adjusted life year gained, a metric considered a good value from a societal perspective.

Women With Type 1 Diabetes at Higher Risk for Death Than Men With the Disease

A recent meta-analysis found that in comparison to men with type 1 diabetes, women with the disease have nearly 40% excess risk of all-cause mortality and twice the excess risk of fatal and nonfatal vascular events (Lancet 2015; dx.doi.org/10.1016/S2213-8587(14)70248-7). The findings support the need for further research to understand the basis for these differences, which could have “profound clinical implications for how women with type 1 diabetes are treated and managed throughout their life course,” according to the investigators.

The authors evaluated 26 studies which involved 214,114 individuals. The primary endpoint for the meta-analysis was all-cause mortality; secondary endpoints were mortality or incident coronary heart disease, stroke, cardiovascular disease, renal disease, cancer, and the combined outcome of accident and suicide.

The authors found the pooled women-to-men ratio of the standardized mortality ratio for all-cause mortality was 1.37 for incident stroke, 1.44 for renal disease, and 1.86 for cardiovascular disease. The “specificity of the observed sex difference for vascular-related outcomes in patients with type 1 diabetes adds to the accumulating evidence suggesting a greater adverse effect of hyperglycemia and diabetes on vascular risk in women than in men,” according to the authors.