Weidmann P, Bianchetti M G, Mordasini R
Curr Med Res Opin. 1983;8 Suppl 3:123-34. doi: 10.1185/03007998309109846.
A prospective evaluation was started in 1976 to study the influence of diuretics alone or combined with beta-blockers on serum lipoproteins in normal or hypertensive subjects. Compared to placebo conditions, 4 or 6-weeks' monotherapy with various diuretics significantly (p less than 0.05) increased the beta-lipoprotein fraction (furosemide, 80 mg/day or chlorthalidone, 100 mg/day; n = 16) or low-density lipoprotein-cholesterol (LDL-C) (chlorthalidone, 100 mg/day, n = 27 men; tienilic acid, 250 mg/day, n = 16 men, clopamide, 5 mg/day, n = 17 men; or muzolimine, 20 to 40 mg/day, n = 13 men or post-menopausal women). No increase in LDL-C was noted in 43 men (32 normal, 11 with mild hypertension) treated with indapamide, 2.5 mg/day. Serum high-density lipoprotein-cholesterol and apoproteins A1, A2 and B were not consistently changed by any of these agents. In women, chlorthalidone (100 mg/day) significantly increased LDL-C in the (100 mg/day) significantly increased LDL-C in the post-menopausal (n = 18) but not in the pre-menopausal (n = 22) state. Increases in LDL-C caused by chlorthalidone monotherapy were prevented or reversed by the addition of a beta-blocker, usually propranolol or atenolol (n = 18); increases in LDL-C during clopamide monotherapy were reversed after the addition of the beta-blocker pindolol (10 mg/day, n = 17). In all studies, variations in beta-lipoprotein or LDL-C levels could not be explained by changes in blood volume, serum glucose or insulin and did not correlate with alterations in blood pressure, plasma potassium, renin, aldosterone, adrenaline or noradrenaline. These observations indicate that various diuretics may increase serum LDL-C in men or post-menopausal women. Pre-menopausal women may often be protected from this side-effect. Long-term studies are now needed to clarify the pathogenic and prognostic relevance of lipoprotein changes induced by diuretics. In the meantime, it is of clinical interest that indapamide had no significant effect on serum lipoproteins and that certain beta-blockers appear to prevent or reverse increases in LDL-C during diuretic treatment in men and post-menopausal women.
1976年开始了一项前瞻性评估，以研究单独使用利尿剂或联合β受体阻滞剂对正常或高血压受试者血清脂蛋白的影响。与安慰剂组相比，使用各种利尿剂进行4或6周的单一疗法显著（p<0.05）增加了β脂蛋白组分（速尿，80毫克/天或氯噻酮，100毫克/天；n=16）或低密度脂蛋白胆固醇（LDL-C）（氯噻酮，100毫克/天，n=27名男性；替尼酸，250毫克/天，n=16名男性，氯吡胺，5毫克/天，n=17名男性；或莫唑胺，20至40毫克/天，n=13名男性或绝经后女性）。每天服用2.5毫克吲达帕胺治疗的43名男性（32名正常，11名轻度高血压）中未发现LDL-C升高。这些药物均未使血清高密度脂蛋白胆固醇和载脂蛋白A1、A2和B持续发生变化。在女性中，氯噻酮（100毫克/天）使绝经后（n=18）女性的LDL-C显著升高，但未使绝经前（n=22）女性升高。氯噻酮单一疗法引起的LDL-C升高可通过加用β受体阻滞剂（通常是普萘洛尔或阿替洛尔，n=18）预防或逆转；氯吡胺单一疗法期间LDL-C的升高在加用β受体阻滞剂吲哚洛尔（10毫克/天，n=17）后逆转。在所有研究中，可以用血容量、血清葡萄糖或胰岛素的变化来解释β脂蛋白或LDL-C水平变化，且与血压、血浆钾、肾素、醛固酮、肾上腺素或去甲肾上腺素的改变无关。这些观察结果表明，各种利尿剂可能会使男性或绝经后女性的血清LDL-C升高。绝经前女性通常可能免受这种副作用的影响。现在需要进行长期研究来阐明利尿剂引起脂蛋白变化的发病机制和预后相关性研究。与此同时，吲达帕胺对血清脂蛋白无显著影响，且某些β受体阻滞剂似乎可预防或逆转男性和绝经后女性利尿剂治疗期间LDL-C升高，这具有临床意义值得关注。
