Background and aim
We sought to determine the association between alanine aminotransferase (ALT) in the normal range and mortality in the absence of liver dysfunction to better understand ALT’s clinical significance beyond liver injury and inflammation.
Methods
A cohort of 2,708 male and 3,461 female adults aged 20–75 years without liver dysfunction (ALT<30 in males & <19 in females, negative viral serologies, negative ultrasound-based steatosis, no excess alcohol consumption) from the National Health and Nutrition Examination Survey (NHANES)-III (1988–1994) were linked to the National Death Index through December 31, 2015. Serum ALT levels were categorized into sex-specific quartiles (Females: <9, 9–11, 11–14, ≥14 IU/L, Male: <12, 12–15, 15–20, ≥20 U/L). The primary outcome was all-cause mortality. Hazard ratios (HRs) were estimated, adjusting for covariates and accounting for the complex survey design.
Results
Relative to males in the lowest quartile (Q1), males in the highest quartile (Q4) had 44% decreased risk of all-cause mortality (aHR [95% CI]: 0.56 [0.42, 0.74]). Females in Q4 had 45% decreased risk of all-cause mortality (aHR [95% CI]: 0.55 [0.40, 0.77]). Males with BMI <25 kg/m2 in Q4 had significantly lower risk of all-cause mortality than Q1; however, this association did not exist in males with BMI ≥25 (BMI<25: 0.36 [0.20, 0.64], BMI≥25: 0.77 [0.49, 1.22]). Risk of all-cause mortality was lower in males ≥50 years than in males<50 (age≥50: 0.55 [0.39, 0.77], age<50: 0.81 [0.39, 1.69]). These age- and BMI-related differences were not seen in females.
Conclusion
ALT within the normal range was inversely associated with all-cause mortality in U.S. adults.
BACKGROUND:
Heart failure (HF) is a leading cause of hospitalization in older adults. Medicare data have been used to assess HF outcomes. However, the validity of ICD-10 diagnosis codes (used since 2015) to identify acute HF hospitalization or distinguish reduced (heart failure with reduced ejection fraction) versus preserved ejection fraction (HFpEF) is unknown in Medicare data.
METHODS:
Using Medicare data (2015–2017), we randomly sampled 200 HF hospitalizations with ICD-10 diagnosis codes for HF in the first/second claim position in a 1:1:2 ratio for systolic HF (I50.2), diastolic HF (I50.3), and other HF (I50.X). The primary gold standards included recorded HF diagnosis by a treating physician for HF hospitalization, ejection fraction (EF)≤50 for heart failure with reduced ejection fraction, and EF>50 for HFpEF. If the quantitative EF was not present, then qualitative descriptions of EF were used for heart failure with reduced ejection fraction/HFpEF gold standards. Multiple secondary gold standards were also tested. Gold standard data were extracted from medical records using standardized forms and adjudicated by cardiology fellows/staff. We calculated positive predictive values with 95% CIs.
RESULTS:
The 200-chart validation sample included 50 systolic, 50 diastolic, 47 combined dysfunction, and 53 unspecified HF patients. The positive predictive values of acute HF hospitalization was 98% [95% CI, 95–100] for first-position ICD-10 HF diagnosis and 66% [95% CI, 58–74] for first/second-position diagnosis. Quantitative EF was available for ≥80% of patients with systolic, diastolic, or combined dysfunction ICD-10 codes. The positive predictive value of systolic HF codes was 90% [95% CI, 82–98] for EFs≤50% and 72% [95% CI, 60–85] for EFs≤40%. The positive predictive value was 92% [95% CI, 85–100] for HFpEF for EFs>50%. The ICD-10 codes for combined or unspecified HF poorly predicted heart failure with reduced ejection fraction or HFpEF.
CONCLUSIONs:
ICD-10 principal diagnosis identified acute HF hospitalization with a high positive predictive value. Systolic and diastolic ICD-10 diagnoses reliably identified heart failure with reduced ejection fraction and HFpEF when EF 50% was used as the cutoff.
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