Diagnostic Value of Aldosterone to Renin Ratio Calculated by Plasma Renin Activity or Plasma Renin Concentration in Primary Aldosteronism: A Meta-Analysis
Primary aldosteronism (PA) is one of the most common endocrine causes of secondary hypertension, with a prevalence of 5% to 10% in the hypertensive population. PA is characterized by excessive production of aldosterone, leading to hypertension, cardiovascular complications, and cerebrovascular events. Early and accurate diagnosis of PA is crucial for effective treatment and prevention of associated complications. The aldosterone to renin ratio (ARR) is a widely used screening tool for PA, calculated using either plasma renin activity (PRA) or plasma renin concentration (PRC). However, the diagnostic efficacy of ARR calculated by these two methods remains inconclusive. This meta-analysis systematically reviews relevant literature to compare the diagnostic performance of ARR calculated by PRC (PAC/PRC) and PRA (PAC/PRA) and provides guidance for clinical diagnosis.
Background and Importance of Primary Aldosteronism
PA is a significant cause of secondary hypertension, often underdiagnosed despite its high prevalence. Patients with PA have a higher risk of cardiovascular and cerebrovascular complications compared to those with essential hypertension (EH). The Endocrine Society Guideline recommends screening for PA in high-risk patients using the ARR. Traditionally, ARR is calculated using plasma aldosterone concentration (PAC) and PRA. However, recent studies suggest that using PRC to calculate ARR may provide more reliable results by avoiding the influence of angiotensinogen concentration, incubation conditions, and pH value on measurement outcomes. Despite these advancements, the diagnostic efficacy of ARR calculated by PRC or PRA remains unclear, necessitating a comprehensive meta-analysis.
Methods and Study Design
This meta-analysis systematically reviewed studies from PubMed, Embase, and Cochrane Library from their inception to March 2021. The inclusion criteria were studies reporting true positive (TP), false positive (FP), true negative (TN), and false negative (FN) values for the diagnosis of PA. Studies with duplicate publications, incomplete information, animal experiments, reviews, and systematic reviews were excluded. Data extraction and quality assessment were independently performed by two researchers, with discrepancies resolved through discussion or consultation with a third party. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool was used to evaluate the methodological quality of the included studies. Statistical analysis was conducted using STATA 15.1, with sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and symmetric area under the curve (SAUC) calculated to assess diagnostic performance.
Results of the Meta-Analysis
A total of 14 studies involving 2638 patients were included in the meta-analysis, with nine studies reporting ARR (PAC/PRC) and five studies reporting ARR (PAC/PRA). The pooled results showed that ARR (PAC/PRC) had a sensitivity of 0.82 (95% confidence interval [CI]: 0.78–0.86), specificity of 0.94 (95% CI: 0.92–0.95), positive LR of 12.77 (95% CI: 7.04–23.73), negative LR of 0.11 (95% CI: 0.07–0.17), and SAUC of 0.982. The DOR for ARR (PAC/PRC) was 180.21. In comparison, ARR (PAC/PRA) had a sensitivity of 0.91 (95% CI: 0.86–0.95), specificity of 0.91 (95% CI: 0.90–0.93), positive LR of 7.30 (95% CI: 2.99–17.99), negative LR of 0.10 (95% CI: 0.04–0.26), and SAUC of 0.976. The DOR for ARR (PAC/PRA) was 155.52.
Subgroup Analysis and Threshold Effects
Subgroup analysis was conducted to explore the influence of different thresholds on diagnostic efficacy. The studies reporting ARR (PAC/PRC) were divided into two groups based on the cut-off value: <35 and ≥35. The results showed that the DOR for the cut-off ≥35 group was significantly higher than the cut-off <35 group (DOR = 340.15, 95% CI: 38.32–3019.66 vs. DOR = 116.40, 95% CI: 23.28–581.92). This suggests that within a certain range, higher thresholds improve diagnostic performance.
Publication Bias and Sensitivity Analysis
Publication bias was assessed using Deek’s funnel plot. For studies reporting ARR (PAC/PRC), the P value was 0.06, indicating no significant publication bias. However, for studies reporting ARR (PAC/PRA), the P value was 0.01, suggesting potential publication bias. Sensitivity analysis was performed by eliminating each study one by one and recalculating the pooled results. The findings indicated that no single study had an excessive impact on the overall results, confirming the stability and reliability of the meta-analysis.
Discussion and Clinical Implications
The meta-analysis demonstrates that both ARR (PAC/PRC) and ARR (PAC/PRA) are effective screening tools for PA. However, ARR (PAC/PRC) exhibits higher diagnostic accuracy and value compared to ARR (PAC/PRA). This is consistent with previous studies highlighting the advantages of PRC over PRA, including better reproducibility, shorter turnaround time, and easier standardization. Despite these advantages, PRA shows higher sensitivity, making it a suitable choice for clinicians prioritizing sensitivity in PA diagnosis.
The analysis also revealed significant heterogeneity among the included studies, primarily due to variations in cut-off values and the selection of control groups. The cut-off values for ARR (PAC/PRA) ranged from 26.35 to 68.28, while those for ARR (PAC/PRC) ranged from 13.10 to 59.66. Subgroup analysis confirmed that higher thresholds improve diagnostic performance, providing valuable insights for clinical practice.
Limitations and Future Directions
This study has several limitations. First, the high heterogeneity among studies may affect the generalizability of the results. Second, potential publication bias in studies reporting ARR (PAC/PRA) could influence the findings. Third, the small number of included studies limits the robustness of the analysis. Future research should focus on larger, well-designed studies to validate these findings and explore additional factors influencing diagnostic performance.
Conclusion
The meta-analysis confirms that ARR (PAC/PRC) and ARR (PAC/PRA) are effective screening tools for PA, with ARR (PAC/PRC) demonstrating higher diagnostic accuracy. Within a certain range, higher thresholds improve diagnostic performance. These findings provide valuable guidance for clinicians in the early and accurate diagnosis of PA, ultimately improving patient outcomes.
doi.org/10.1097/CM9.0000000000001906
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