Regarding: Adherence to guideline-recommended care of late-onset hypertension in females versus males: A population-based cohort study

Dear Editor,

Bugeja et al. offered significant insights into the management of late-onset hypertension [1]; however, several methodological and interpretive issues warrant further scrutiny.

The study's statistical analysis, while robust, may overlook subtle but clinically significant interactions between sex and other covariates. For instance, the adjusted hazard ratios (aHR) for the prescription of antihypertensive medications (aHR 0.98 for females vs. males) suggest a minor statistical difference that the authors deem non-clinically significant. However, given the large sample size, even small differences can translate into meaningful impacts at the population level. A more nuanced statistical approach, such as the use of interaction terms and stratified analyses, might uncover important sex-specific differences in treatment efficacy and adherence. Austin et al. emphasized the importance of understanding interactions in epidemiological research, which can provide a more detailed understanding of how sex may influence treatment outcomes [2].

Furthermore, the study's reliance on retrospective data from administrative databases introduces potential biases. Although the authors adjusted for numerous covariates, the inherent limitations of such data sources, such as coding inaccuracies and unmeasured confounders, cannot be fully mitigated. The use of the ICD-10 coding system for hypertension diagnosis and subsequent treatment prescriptions may not accurately reflect the clinical nuances of patient management. Quan et al. noted that administrative data, while useful, often lack the granularity needed for precise clinical studies, potentially leading to misclassification biases that can skew results [3]. Future research should consider these limitations and possibly integrate clinical data to enhance the accuracy of findings.

The interpretation of the results also warrants reconsideration. The authors conclude that there are no clinically meaningful sex-based differences in the initial management of late-onset hypertension. However, this interpretation might be premature. The study finds that females are less likely to be prescribed certain antihypertensive medications, such as Angiotensin-converting enzyme (ACE) inhibitors, compared to males (aHR 0.995). This subtle difference, while statistically modest, could reflect underlying disparities in clinical decision-making processes, possibly influenced by provider biases or patient preferences. Evidence has shown that such disparities can have long-term implications for health outcomes, suggesting the cumulative impact of small biases in clinical care over time [4]. This highlights the need for a more detailed examination of prescribing practices and their long-term effects on patient outcomes.

Lastly, although the discussion section is comprehensive, it occasionally overgeneralizes findings. The assertion that “females benefit more from antihypertensive medication” lacks sufficient empirical backing within the context of the presented data. The referenced studies predominantly focus on broader cardiovascular outcomes rather than the specific cohort and context of late-onset hypertension examined here. Future research should aim to isolate the effects of antihypertensive therapies in older females more rigorously, potentially through randomized controlled trials or more detailed observational studies. Benetos et al. suggested that older populations with significant incidence of hypertension require tailored management strategies to address their unique needs [5].

Shanshan Huang, Yanli Chen, and Dan Shan: Manuscript writing and study design. Renquan Wang: Manuscript revision and study design.

The authors declare no conflicts of interest.

None.