Primary aldosteronism (PA), characterized by the autonomous production of aldosterone, is a common and potentially curable disease of secondary hypertension [1
]. PA leads to 5−13% of patients developing resistant hypertension [3
]. On the other hand, aldosterone increases oxidative stress and inflammation, contributing to impaired pancreatic beta-cell function and diminished skeletal muscle insulin metabolic signaling. PA patients have a high incidence of cardiovascular (CV) events in comparison with essential hypertension (EH) patients [4
]. Furthermore, the higher prevalence of metabolic syndrome was expected as a result of the increased rate of CV events observed in patients with PA compared to EH [4
The American College of Cardiology (ACC) and the American Heart Association (AHA) released new guidelines for statin therapy based on the latest cholesterol management guidelines [7
]. The ACC/AHA guidelines introduced a prediction model and lowered the threshold for treatment with statins to a 10-year atherosclerotic cardiovascular disease (ASCVD) risk of 7.5%. The ACC/AHA guidelines for the management of cholesterol increase the number of adults who would be eligible for statin therapy [8
] and have better predictive value for cardiovascular (CV) events [9
] compared with the previous Adult Treatment Panel III (ATP-III) guidelines [2
]. Based on a Cardiovascular Life Expectancy Model to estimate the advantages of risk factor modification in the prevention of CV events, forecasting advantages of using statin for the therapy of hyperlipidemia have shown that middle-aged patients have the highest level of benefits [10
]. However, the implications of this updated guideline for statin recommendations have not been addressed in a population at high risk for a CV event, mainly primary aldosteronism patients.
Middle-aged hypertensive patients with PA and EH were prospectively studied at diagnosis. This study aimed to evaluate and validate the incident ASCVD risk, defined as the development of a CV and stroke event within a 10-year period, taking into account several risk factors simultaneously, according to the ACC/AHA guidelines, in patients with PA and EH. Furthermore, we studied the relationship of plasma aldosterone concentration (PAC) and the use of statins based on the suggestion of the guidelines for the prevention of ASCVD.
Our study indicated that the estimated ASCVD risk and the recommended statin use according to the algorithm by the ACC/AHA had good discriminative power in the ratio of 10-year ASCVD in both PA and EH patients. Besides, higher levels of PAC (cut-off point: PAC = 60 ng/dL) contributed to more recommended statin therapy according to ACC/AHA guidelines.
The present research is the first documented study to validate the ACC/AHA guidelines in PA patients. Patients with PA can often be established with a higher risk of left ventricular hypertrophy, myocardial fibrosis, and diastolic dysfunction than EH patients [18
]. Accumulating evidence suggests that the role of PA is considered one of the more frequent etiologies of secondary hypertension. Increased levels of aldosterone-mediated effects are present in situations including heart failure, PA and excessive salt intake. Hyperaldosteronism accompanied with klotho deficiency gain recognition from a disproportionally increased risk of cardiovascular damage and metabolic diseases [5
]. The suppression of renin by excess aldosterone is linked with evidence of vascular injury, worsening blood pressure, and renal or cardiovascular events after target management in PA patients compared with EH patients [20
]. Abnormal glucose metabolism due to insulin resistance appears to be linked to aldosterone overproduction and appears to be the major contributor to metabolic dysfunction in PA patients [25
]. In agreement with our report, the distribution of each component of metabolic syndrome showed a higher frequency of ASCVD risk in PA patients than EH patients, whereas there was no difference between the two groups with respect to diabetes, abdominal obesity, BMI, and smoking status [26
]. This is in agreement with the fact that aldosterone excess may lead to CV damage by mechanisms independent of a hypertensive effect [27
The efficacy of statin therapy in reducing the risk of ASCVD has been well established [28
]. Baudrand and his colleagues observed that the pleiotropic effects of statins mediated aldosterone secretion in adrenal cells. Lipophilic statins had a greater effect in suppressing aldosterone production than a hydrophilic statin. Further, potassium-stimulated aldosterone could be interrupted immediately by a 33% decrease in statins; the condition suggests that statins reduce PAC from the angiotensin II receptor type 1. Consistent with the concept, mesangial cells represent that statins inhibit acute aldosterone production induced by angiotensin II in vitro, in addition to long-term statin treatment blocking the expression of aldosterone synthase in the kidney in rats [29
]. Recent evidence also demonstrates that proper statin use is related to decreased CV morbidity and mortality, particularly with high-risk patients [28
]. This fact emphasizes the importance of better biomarkers for recommended statin therapy in high-risk patients. Our finding of PAC cut-off points (PAC > 60 ng/dL) provides the opportunity for clinicians to identify those high-risk individuals who may benefit from targeted patient counseling and early statin therapy.
Clinicians should pay attention to not only the estimated ASCVD risk, but also the presence or absence of metabolic syndrome in high-risk patients. Metabolic syndrome is a complex condition caused by insulin resistance accompanying abnormal adipose function. It consists of the risk factors for coronary heart disease, as well as for diabetes [30
]. It is well known that higher prevalence of metabolic syndrome is found in PA patients, as well as the favorable effect of aldosterone excess removal on glucose metabolism alterations and left ventricular mass index [31
]. Among the components of metabolic syndrome, lower HDL-c and hypertension were prevalent in PA patients in our study. Besides, we further provided more evidence that factors of metabolic syndrome in the ACC/AHA guidelines helps to predict 10-year ASCVD events.
There were some limitations in our study. Even though this was a prospective study, we did the retrospective analysis of the estimated ASCVD risk according to the ACC/AHA guidelines. The lack of information on lipid values limited the recruited patients. Second, the registration of smoking was based on self-reports, and therefore there may be underestimated. Finally, we have concentrated on the population between 40 and 75 years of age because the new guidelines are unknown outside this age range. Furthermore, a new recommended statin use model based on PAC level needs more studies on indicator performance and cost-effectiveness analyses.
In conclusion, the recommended statin uses by the ACC/AHA guidelines had good discriminative power on both PA and EH patients. Besides, patients with elevated aldosterone levels (PAC > 60 ng/dL) are compatible with the recommended timing of statin use on ASCVD control in middle-aged high-risk patients. We conclude that in clinical practice, the estimated ASCVD risk by the ACC/AHA guidelines should be evaluated for both primary and secondary ASCVD prevention, especially in PA patients. Because proper statin therapy is essential for clinical benefit, promoting optimal drug utilization based on PAC in all hypertensive patients is a reasonable strategy. Further influence of statin therapy on correcting metabolic abnormalities in middle-aged high-risk patients warrants further study.