The relationship between age and ALT as an inversed linearly trend or formed as an inverted U-wave along quantiles of age-groups is usually reported as representative for the entire study population but is recognized in the present study as confined to either sex group, respectively men and women. Furthermore, ALT is associated with metabolic components and clinical CVD risk factors, but BMI was the only one independently associated with ALT in both sexes in a multivariate analysis.
A linear and inversed relationship between age and ALT in both sexes is reported in cross-sectional and longitudinal studies [17, 22]. Although the present study participants were younger in comparison, it confirmed a linear age-ALT trend that persisted after adjusting for covariates, but in men only. An Australian community study in 1673 elderly men (≥ 70 years) designed as a survival analyses, showed an inversed relationship between age and ALT like the findings in the male group here . That study found low ALT to be associated with reduced survival partly due to high age, but the mechanisms is otherwise largely unknown . However, obesity without accompanied CVD has been related to increased survival (the obesity paradox) . Like here, age and BMI were negatively correlated in men contrasting the positive relationship in women. Accordingly, the third U.S. National Health and Nutrition Examination Survey (n = 5724) found positive associations between age and male sex in relation to ALT which abolished in a multivariate analysis. Also, BMI remained significantly associated with ALT . Age, sex and BMI also influenced transaminase levels in children and adolescents. In girls, ALT declined from infancy until 4 years of age, then increased to peak at 16 years. The same U-form was found for boys although a little delayed . Boys had higher ALT levels than girls, and BMI correlated stronger with ALT in boys .
Despite different age-ALT curves between men and women in the present study, the relationships between ALT and CVD risk factors including glucose were approximately the same. In women, an inversed U-form with significant and opposite directed age-ALT correlations on both sides of the 60-year cut-off is demonstrated. A similar pattern with ALT-maximum at 65-year of age was found equal for both sexes in a recent cross-sectional study in 10,000 non-diabetic subjects . By showing a similar trend for age vs. fasting glucose levels, glucose was suggested to entail a joint effect on the ALT levels across ages . The same phenomenon is demonstrated in a study that included subjects living in aged home and participants recruited from three general practices (n = 335). ALT values was distributed along an inversed U-shaped curve with a peak level between 40–55 years . In parallel, ALT increased until the third decade in men and the fifth decade in women in a large Italian study where ALT additionally associated positively with BMI, glucose and lipids .
The sex-difference in ALT vs. age in the present study is not shown in previous studies, and the data otherwise do not point to any certain mechanism. A study in an obese cohort from the same area, showed an association between ALT and the muscular component of body composition in both sexes, but ALT was associated with fat mass in men only . Furthermore, ALT was positively correlated with glucose, glycated haemoglobin and cholesterol in obese women . ALT is higher in men than women but whether this is due to different body composition, sex hormones or diverging effect of confounders is unknown [27, 28]. Thus, ALT predicted prevalent coronary heart disease in men in an European-American study . Although the Tromsø study provides robust data, the evidence of the present cross-sectional study confines to associations between data, which itself might contribute to differences in comparisons with others.
Perspectives and significance
These data confirms an independent and equal association between ALT and BMI in both sexes . The sex-specific variations in ALT levels seem to be unrelated to CVD-related risk factors and is largely unexplained. Data from studies on ALT should be analysed sex-stratified.