社区中胆固醇水平、羟甲基戊二酰辅酶A还原酶抑制剂治疗与主动脉瓣狭窄进展的关联

Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community.

作者信息

Bellamy Michael F, Pellikka Patricia A, Klarich Kyle W, Tajik A Jamil, Enriquez-Sarano Maurice

机构信息

Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

出版信息

J Am Coll Cardiol. 2002 Nov 20;40(10):1723-30. doi: 10.1016/s0735-1097(02)02496-8.

DOI:10.1016/s0735-1097(02)02496-8

PMID:12446053

Abstract

OBJECTIVES

This study was designed to analyze the association among cholesterol levels, lipid-lowering treatment, and progression of aortic stenosis (AS) in the community.

BACKGROUND

Aortic stenosis is a progressive disease for which there is no known medical treatment to prevent or slow progression. Despite plausible pathologic mechanisms linking hypercholesterolemia to AS progression, clinical studies have been inconsistent and affected by referral bias, and the role of lipid-lowering therapy is uncertain.

METHODS

We determined the association between blood cholesterol levels and progression of native AS (assessed by Doppler echocardiography at baseline and at least six months later; mean interval, 3.7 +/- 2.3 years) in a community-based study of 156 patients (age 77 +/- 12 years; 90 men). Thirty-eight patients received statin treatment during follow-up.

RESULTS

In untreated subjects, mean gradient increased from 22 +/- 12 mm Hg to 39 +/- 19 mm Hg, and aortic valve area (AVA) decreased from 1.20 +/- 0.35 cm(2) to 0.91 +/- 0.33 cm(2) (both p < 0.001). The annualized change in AVA was -0.09 +/- 0.17 cm(2)/year (-7% +/- 13%/year). Neither total cholesterol (r = -0.01, p = 0.92) nor low-density lipoprotein cholesterol (r = 0.01; p = 0.88) showed a significant correlation to AS progression. Nevertheless, progression of AS was slower in patients receiving statins compared with untreated patients (decrease in AVA -3 +/- 10% vs. -7 +/- 13% per year, respectively; p = 0.04), even when adjusted for age, gender, cholesterol, and baseline valve area (p = 0.04). The association of statin treatment with slower progression was confirmed when analysis was restricted to patients coming for a systematic follow-up (p=0.02). The odds ratio of AS progression with statin treatment was 0.46 (95% confidence interval, 0.21 to 0.96).

CONCLUSIONS

In the community, progression of AS shows no trend of association with cholesterol levels. Statin treatment, however, is associated with slower progression, suggesting that the effects of statin treatment on progression of AS should be pursued with appropriate clinical trials.

摘要

目的

本研究旨在分析社区中胆固醇水平、降脂治疗与主动脉瓣狭窄（AS）进展之间的关联。

背景

主动脉瓣狭窄是一种进行性疾病，目前尚无已知的药物治疗方法来预防或减缓其进展。尽管有合理的病理机制将高胆固醇血症与AS进展联系起来，但临床研究结果并不一致，且受到转诊偏倚的影响，降脂治疗的作用尚不确定。

方法

在一项针对156例患者（年龄77±12岁；男性90例）的社区研究中，我们确定了血液胆固醇水平与原发性AS进展（通过基线及至少6个月后的多普勒超声心动图评估；平均间隔3.7±2.3年）之间的关联。38例患者在随访期间接受了他汀类药物治疗。

结果

在未接受治疗的受试者中，平均压差从22±12mmHg增加到39±19mmHg，主动脉瓣面积（AVA）从1.20±0.35cm²减少到0.91±0.33cm²（两者p<0.001）。AVA的年化变化为-0.09±0.17cm²/年（-7%±13%/年）。总胆固醇（r=-0.01，p=0.92）和低密度脂蛋白胆固醇（r=0.01；p=0.88）与AS进展均无显著相关性。然而，与未接受治疗的患者相比，接受他汀类药物治疗的患者AS进展较慢（AVA每年下降分别为-3±10%和-7±13%；p=0.04），即使在调整年龄、性别、胆固醇和基线瓣膜面积后也是如此（p=0.04）。当分析仅限于前来进行系统随访的患者时，他汀类药物治疗与较慢进展之间的关联得到证实（p=0.02）。接受他汀类药物治疗的AS进展的优势比为0.46（95%置信区间，0.21至0.96）。