他汀或可抑製高血壓和糖尿病患者醛固酮的分泌

作者:小田 譯 來源:醫學論壇網 日期:15-10-21

        他汀類藥物確實可減少心血管死亡率,並且似乎這種益處是獨立於降脂治療特性的。多國學者近期評估了他汀類藥物是否可調節醛固酮的分泌,後者可導致心血管疾病。結果表明,高血壓糖尿病患者應用他汀與醛固酮分泌減少有關,這一影響似乎在使用親脂性他汀和較大劑量應用者中最為明顯。相關論文近期發表於《循環》(Circulation)雜誌。

        研究者們對兩項幹預試驗中的受試者檢測了腎上腺激素。在第一項試驗的高血壓受試者中,分析其基線以及高鈉和低鈉飲食後血管緊張素-II刺激後的醛固酮水平(1122個觀察對象,15%接受為期3個月的他汀類藥物治療)。結果顯示,在校正模型中,他汀使用者的醛固酮水平低了33%(P< 0.001)。皮質醇水平不受他汀影響。在次要分析中,親脂性他汀和較大劑量他汀使用者的醛固酮水平最低。他汀使用者的血壓較低,且血壓的鹽敏感性減少(P=0.001)。

        在第二項研究中,研究者們檢測了高鹽飲食糖尿病患者血管緊張素-II刺激後的醛固酮水平(143個觀察對象,79%是他汀類藥物使用者)。研究結果再次證明他汀使用者的醛固酮水平較低(低了26%,P=0.006),尤其是那些用親脂性他汀者。

        大鼠腎上腺球狀帶細胞的體外研究也再次驗證了親脂性他汀可強烈抑製醛固酮,而不抑製皮質酮。

        參考文獻:Rene Baudrand,et al. CIRCULATIONAHA.115.016759Published online before print October 2, 2015,doi: 10.1161/CIRCULATIONAHA.115.016759

Statin Use and Adrenal Aldosterone Production in Hypertensive and Diabetic Subjects
1. Rene Baudrand1*;
2. Luminita H. Pojoga2;
3. Anand Vaidya2;
4. Amanda E. Garza2;
5. Paul A. Vöhringer3;
6. Xavier Jeunemaitre4;
7. Paul N. Hopkins5;
8. Tham M. Yao2;
9. Jonathan Williams2;
10. Gail K. Adler2;
11. Gordon H. Williams2
-Author Affiliations
1. 1Brigham and Women's Hospital, Harvard Medical School, Boston, MA & School Of Medicine, Pontificia Universidad Catolica De Chile, Santiago, Chile
2. 2Brigham and Women's Hospital, Harvard Medical School, Boston, MA
3. 3Hospital Clinico, FacultadMedicina Universidad de Chile, Santiago, Chile and Tufts Medical Center, Tufts University School of Medicine, Boston, MA
4. 4Centre Investigation Clinique, HôpitalEuropéen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Universite Paris Descartes, Paris, France
5. 5University of Utah School of Medicine, Salt Lake City, UT
1. ↵* Dept of Endocrinology, School Of Medicine, Pontificia Universidad Catolica De Chile, Santiago 8330074, Chile rbaudran@uc.cl
Abstract
Background—Statins substantially reduce cardiovascular mortality and appear to have beneficial effects independent of their lipid lowering properties. We evaluated the hypothesis that statin use may modulate the secretion of aldosterone, a well-known contributor to cardiovascular disease.
Methods and Results—We measured adrenal hormones in two intervention studies. In study 1 in hypertensive subjects, aldosterone was analyzed at baseline and after angiotensin-II stimulation (AngII) on both high (HS) and low sodium (LS) diets (1122 observations, 15% on statins > 3 months). Statin users had 33% lower aldosterone levels in adjusted models (p < 0.001). Cortisol was not modified by statins. In secondary analyses, the lowest aldosterone levels were seen with lipophilic statins and with higher doses. Statin users had lower blood pressure (BP) and reduced salt sensitivity of BP (p=0.001). In study 2, aldosterone was measured in diabetic patients on a HS diet, before and after AngII stimulation (143 observations, 79% statin users). Again, statin users had 26% lower aldosterone levels (p =0.006), particularly those using lipophilic statins. Ex vivo studies in rat adrenal glomerulosa cells confirmed that lipophilic statins acutely inhibited aldosterone, but not corticosterone, in response to different secretagogues.
Conclusions—Statin use among hypertensive and diabetic subjects was associated with lower aldosterone secretion in response to AngII and LS diet in two human intervention studies. This effect appeared to be most pronounced with lipophilic statins and higher doses. Future studies to evaluate whether aldosterone inhibition may partially explain the robust cardioprotective effects of statins are warranted.

關鍵字:他汀,高血壓,糖尿病患者,醛固酮

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