Sex, racial differences and healthy aging in normative reference ranges on diastolic function in Ethnic Asians: 2016 ASE guideline revisited

Abstract

Background: Diastolic dysfunction (DD) has shown to be a hallmark pathological intermediate in the development of heart failure with preserved ejection fraction (HFpEF). We aim to establish age- and sex-stratified normal reference values of diastolic indices and to explore racial-differences.

Methods: We explored age- and sex-related structural/functional alterations from 6023 healthy ethnic Asians (47.1 ± 10.9 years, 61.3% men) according to 2016 American Society of Echocardiography (ASE) diastolic dysfunction (DD) criteria. Racial comparisons were made using data from London Life Sciences Prospective Population (LOLIPOP) study.

Results: Age- and sex-based normative ranges (including mean, median, 10% and 90% lower and upper reference values) were extracted from our large healthy population. In fully adjusted models, advanced age was independently associated with cardiac structural remodeling and worsened diastolic parameters including larger indexed LA volume (LAVi), lower e', higher E/e', and higher TR velocity; all p < 0.001), which were more prominent in women (P interaction: <0.05). Broadly, markedly lower e', higher E/e' and smaller LAVi were observed in ethnic Asians compared to Whites. DD defined by 2016 ASE criteria, despite at low prevalence (0.42%) in current healthy population, increased drastically with advanced age and performed perfectly in excluding abnormal NT-proBNP (≥125 pg/mL) (Specificity: 99.8%, NPV: 97.6%).

Conclusion: This is to date the largest cohort exploring the normative reference values using guideline-centered diastolic parameters from healthy Asians, with aging played as central role in diastolic dysfunction. Our observed sex and ethnic differences in defining healthy diastolic cut-offs likely impact future clinical definition for DD in Asians.

Keywords: American Society of echocardiography (ASE); Diastolic dysfunction (DD); Ethnic asians; Heart failure (HF); N-terminal pro-brain natriuretic peptide (NT-proBNP).