Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP)-the age-related clonal expansion of blood stem cells with leukemia-associated mutations-is a novel cardiovascular risk factor. Whether CHIP remains prognostic in individuals with established atherosclerotic cardiovascular disease (ASCVD) is less clear. OBJECTIVES: This study tested whether CHIP predicts adverse outcomes in individuals with established ASCVD. METHODS: Individuals aged 40 to 70 years from the UK Biobank with established ASCVD and available whole-exome sequences were analyzed. The primary outcome was a composite of ASCVD events and all-cause mortality. Associations of any CHIP (variant allele fraction ≥2%), large CHIP clones (variant allele fraction ≥10%), and the most commonly mutated driver genes (DNMT3A, TET2, ASXL1, JAK2, PPM1D/TP53 [DNA damage repair genes], and SF3B1/SRSF2/U2AF1 [spliceosome genes]) with incident outcomes were compared using unadjusted and multivariable-adjusted Cox regression. RESULTS: Of 13,129 individuals (median age: 63 years) included, 665 (5.1%) had CHIP. Over a median follow-up of 10.8 years, any CHIP and large CHIP at baseline were associated with adjusted HRs of 1.23 (95% CI: 1.10-1.38; P < 0.001) and 1.34 (95% CI: 1.17-1.53; P < 0.001), respectively, for the primary outcome. TET2 and spliceosome CHIP, especially large clones, were most strongly associated with adverse outcomes (large TET2 CHIP: HR: 1.89; 95% CI: 1.40-2.55; P <0.001; large spliceosome CHIP: HR: 3.02; 95% CI: 1.95-4.70; P < 0.001). CONCLUSIONS: CHIP is independently associated with adverse outcomes in individuals with established ASCVD, with especially high risks observed in TET2 and SF3B1/SRSF2/U2AF1 CHIP.

Trends in cholesterol testing during the COVID-19 pandemic: COVID-19 and cholesterol testing.

OBJECTIVE: To characterize trends in cholesterol testing since the start of the COVID-19 pandemic. METHODS: We extracted testing for total cholesterol performed in adults ≥40 years old within the Mass General Brigham healthcare system between March and September 2020, as well those performed between March and September 2019 (reference period). Weekly cholesterol testing rates during the 2020 vs. 2019 study periods were compared using the paired samples t-test. Secondary analyses compared testing volumes and patient characteristics during the first vs. second half of the 2020 study period. RESULTS: The study sample included 296,599 tests for total cholesterol performed in 220,215 individuals. The mean (SD) weekly cholesterol tests performed were 6,361 (682) in 2019 vs. 3,867 (2,373) in 2020 (P = 2.6 × 10-5), representing an overall decline of 39.2%. However, weekly testing rates in 2020 were not uniform. Greatest reductions coincided with the "first wave" of the pandemic (March-May 2020), with up to 92% reductions in testing observed. In the first 14 weeks of each study period (March to mid-June), weekly testing rates were 71.8% lower in 2020. Among individuals tested in 2020, those tested between March and mid-June had substantially lower total cholesterol compared with individuals tested after mid-June (174.2 vs. 181.5 mg/dL, P<2.2 × 10-16). CONCLUSIONS: In a large integrated healthcare system, cholesterol testing rates were 39% lower between March-September 2020 compared with the same time period in 2019. Mechanisms for safely facilitating cholesterol testing and management for high-risk patients will be important as COVID-19 re-surges across the U.S. until widespread vaccination and population immunity allow resumption of routine preventive care.