Prolactin Levels, Endothelial Dysfunction, and the Risk of Cardiovascular Events and Mortality in Patients with CKD

Abstract

SummaryBackground and objectives Both prolactin clearance and production are altered in CKD. In nonrenal populations, emerging evidence suggests that prolactin participates in the atherosclerotic process. Given the elevated cardiovascular risk of CKD, this study examined links between prolactinemia, vascular derangements, and outcomes.Design, setting, participants, & measurements This observational study was conducted in two cohorts: one with 457 nondialyzed CKD patients (mean age 52612 years; 229 men) with measurements of flow-mediated dilation (FMD) and carotid intima-media thickness and one with 173 hemodialysis patients (65612 years; 111 men) with measurements of pulse wave velocity (PWV). Patients were followed for cardiovascular events (n=146, nondialyzed cohort) or death (n=79, hemodialysis cohort).Results Prolactin levels increased along with reduced kidney function. Prolactin significantly and independently contributed to explain the variance of both FMD (in nondialyzed patients) and PWV (in hemodialysis patients), but not intima-media thickness. In Cox analyses, the risk of cardiovascular events in nondialyzed patients increased by 27% (hazard ratio [HR], 1.27; 95% confidence interval [95% CI], 1.17-1.38) for each 10 ng/ml increment of prolactin. Similarly, the risk for all-cause and cardiovascular mortality in hemodialysis patients increased by 12% (HR, 1.12; 95% CI, 1.06-1.17) and 15% (HR, 1.15; 95% CI, 1.08-1.21), respectively. This was true after multivariate adjustment for confounders and after adjustment within the purported causal pathway (FMD or PWV).Conclusions Prolactin levels directly associated with endothelial dysfunction/stiffness and with increased risk of cardiovascular events and mortality in two independent cohorts of CKD patients.

Lactation protects against myocardial ischemia-reperfusion injury in rats

“…Few studies have investigated the potential role of prolactin in the increased risk of cardiovascular events, e.g. essential hypertension, the heart failure that accompanies Peripartum cardiomyopathy, and arrhythmias (7,22). On the other hand, the positive influence of prolactin on the cardiovascular system was shown.…”

Hormones and Arterial Stiffness in Patients with Chronic Kidney Disease

“…Testosterone may also affect the vascular bed by regulating structural elements of the arterial wall, including collagen, elastin and fibrillin-1 56) . In the Baltimore Longitudinal Study of Aging, a low serum testosterone level was found to be a risk factor for AS, suggesting a cause and effect relation-in the CKD 5D patients 37) . The authors suggested that prolactin retention in CKD patients may be a contributing factor to vascular derangement and worse cardiovascular outcomes.…”

“…The major risk factors for an increased level of prolactin are reduced renal clearance and increased production of the hormone 36) . Hyperprolactinemia is associated with infertility, gynecomastia, galactorrhea, loss of libido and mortality in CKD patients 37) .…”

Metabolic syndrome associated with hyperprolactinemia: A new indication for dopamine agonist treatment?

“…In patients with chronic kidney disease, PRL level is directly associated with endothelial dysfunction and within increased risk of cardiovascular events and mortality [12]. Furthermore, even with PRL levels in the normal range, a positive association has been found between higher PRL tertiles and all-cause and cardiovascular mortality in both sexes and cancer deaths in men [6].…”

“…However, the PRL multiple metabolic effects, leading to metabolic syndrome, are well-documented in animal and human cell lines studies [2][3][4]. Furthermore, several clinical studies with a few patients-have shown us the metabolic benefit of hyperprolactinemia treatment [1,[7][8][9][10][11][12].…”