Impact of Macroprolactinemia on Cardiometabolic Effects of Atorvastatin in Women With Hypercholesterolemia

https://doi.org/10.1016/j.amjcard.2019.07.017Get rights and content

Premenopausal women with macroprolactinemia are characterized by increased cardiometabolic risk. No previous study has investigated the impact of any lipid-lowering agent on circulating levels of cardiometabolic risk factors in patients with elevated macroprolactin content. We studied 2 groups of women matched for age, body mass index, plasma lipids, and blood pressure: 12 women with macroprolactinemia and 14 women with prolactin levels within the reference range. Because of coexistent isolated hypercholesterolemia, all subjects were then treated with atorvastatin (20 mg daily). Glucose homeostasis markers, plasma lipids, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before entering the study and 6 months later. The treatment arms differed in baseline values of hsCRP and 25-hydroxyvitamin D, as well as in insulin sensitivity. Atorvastatin decreased total and low-density lipoprotein cholesterol levels stronger in women without than in women with macroprolactinemia. In normoprolactinemic women, atorvastatin decreased circulating levels of uric acid, hsCRP, fibrinogen, homocysteine, and increased concentrations of 25-hydroxyvitamin D, whereas in women with macroprolactinemia the drug decreased levels of hsCRP and homocysteine, as well as impaired insulin sensitivity. Both study groups differed in post-treatment insulin sensitivity and post-treatment values of prolactin before polyethylene glycol precipitation, macroprolactin, total cholesterol, low-density lipoprotein cholesterol, glycated hemoglobin, uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. In conclusion, the obtained results suggest that macroprolactinemia may attenuate cardiometabolic effects of atorvastatin.

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Methods

The study population was selected among adult women (aged 35 to 65 years) with elevated cholesterol levels, defined as total cholesterol concentrations more than 200 mg/dl and low-density lipoprotein (LDL) cholesterol concentrations above 130 mg/dl, complying with the lifestyle modification for more than 3 months before entering the study. The first group included 12 women meeting the following criteria of macroprolactinemia: (1) total prolactin levels more 40 ng/ml found on 2 different

Results

At baseline, there were no significant differences between the participants with and without macroprolactinemia in age, body mass index, smoking habits, fasting and 2-hour postload plasma glucose, glycated hemoglobin, plasma lipids, uric acid, fibrinogen and homocysteine (Table 1). Expectedly, both study groups differed in prolactin concentrations before polyethylene glycol precipitation and in macroprolactin content but not in prolactin concentrations after polyethylene glycol precipitation.

Discussion

Compared with control subjects, women with macroprolactinemia were characterized by increased circulating levels of hsCRP, higher values of HOMA1-IR and decreased levels of 25-hydroxyvitamin D. Similar differences were reported previously between women with elevated content of big-big prolactin not selected for plasma lipids and healthy young women with normal lipid levels.9 The participants of the present study were older (50 ± 8 years) than women participating in the previous one (34 ± 7

Disclosures

The authors declare that they have no conflict of interest.

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    • Funding:This work was not supported by any external sources of funding.

    Ethical Approval:All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments.

    Institutional Approval: The study was approved by the Bioethical Committee of the Medical University of Silesia.

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