Subclinical Primary Aldosteronism Raises Risk of MACE Even With Normal BP, Suggests Study
Canada: A study published in Circulation found that subclinical primary aldosteronism significantly increases the risk of major adverse cardiovascular events (MACEs)—including heart attack, stroke, and heart failure—even among individuals with normal blood pressure. The findings, drawn from data on 2,017 Canadian adults, highlight the dangers of mild renin-independent aldosterone excess and suggest that this condition may be far more clinically relevant than previously understood.
The research, conducted by Rémi Goupil and colleagues from Hôpital de Sacré-Cœur de Montréal, analyzed participants from the population-based CARTaGENE cohort in Québec, Canada. Adults aged 40 to 69 years had their aldosterone and renin levels measured at baseline between 2009 and 2010, with follow-up data collected over a median period of 10.8 years through provincial healthcare databases.
The study examined the relationship between renin and aldosterone levels, the aldosterone-to-renin ratio (ARR), and the incidence of MACEs, including myocardial infarction, stroke, cardiovascular death, and hospitalization for heart failure.
Based on the study, the researchers reported the following findings:
- During the follow-up period, 57 participants (3%) experienced a major adverse cardiovascular event (MACE).
- Individuals with lower renin concentrations had a significantly higher risk of MACEs (adjusted hazard ratio [aHR]: 2.22).
- A higher aldosterone-to-renin ratio (ARR) was also linked to an increased risk (aHR: 2.43), independent of blood pressure levels.
- Absolute aldosterone concentration alone did not strongly predict outcomes, highlighting the importance of the renin-aldosterone balance.
- Thresholds identified for higher cardiovascular risk were a renin concentration of ≤4.0 ng/L and an ARR of ≥70 pmol/L per ng/L.
- Even among participants with an average blood pressure of 129/76 mm Hg and only 27% diagnosed with hypertension, these subclinical biochemical markers were tied to a notably increased risk of adverse cardiovascular outcomes.
According to the authors, the findings challenge traditional diagnostic approaches to primary aldosteronism, which have historically focused on overt disease in hypertensive patients. The study suggests that subclinical, renin-independent aldosterone excess likely affects a much broader portion of the population and carries meaningful cardiovascular risk.
While the research is groundbreaking, the authors caution that the study was observational and cannot establish causation. Other limitations include reliance on single-point hormone measurements, potential unmeasured confounders, and a study population composed predominantly of White participants, limiting generalizability to other racial groups. Despite these caveats, sensitivity analyses confirmed the robustness of the associations observed.
The implications of this work are significant. If further research confirms that early detection and intervention for subclinical primary aldosteronism can mitigate cardiovascular risk, it could prompt a shift in screening and management strategies, potentially incorporating renin and ARR assessments even in individuals with normal or mildly elevated blood pressure.
The study emphasizes the need to recognize subclinical PA as a hidden driver of cardiovascular disease and calls for future trials to explore whether early initiation of targeted therapies, such as mineralocorticoid receptor antagonists, can reduce MACEs in this underdiagnosed population.
Reference:
https://doi.org/10.1161/CIRCULATIONAHA.124.073507
