背景:外周动脉疾病(PAD)与高发病率和高死亡率相关,通常被描述为冠心病。在其他适应症中,他汀类药物被推荐用于动脉粥样硬化性心血管疾病(ASCVD)的一级预防。因此,了解事件PAD的纵向关系对于未来如何预防疾病的研究是必要的。抑郁症使心血管疾病(CVD)患者正确坚持药物治疗的能力复杂化,然而,抑郁症对他汀类药物使用与PAD事件之间关系的影响研究不足.患有PAD的人比没有PAD的人有更高的抑郁症状发生率。美国黑人和西班牙裔人口受PAD和抑郁症的影响不成比例,但有关种族或抑郁症对他汀类药物使用与PAD发作之间关系的改善作用的研究却很少。虽然75-84岁的他汀类药物使用率最高,但很少有证据表明有利的风险-收益平衡。因此,在这个项目中,我们研究了他汀类药物使用与周围动脉疾病的关系,以及这种关系是否因种族/民族而改变,抑郁症状,或年龄。
方法:我们使用了从第1次就诊(2000年)到第6次就诊(2020年)的多种族动脉粥样硬化研究(MESA)参与者的数据,这些参与者在第1次、第3次就诊和第5次就诊时分别测量了踝肱指数(ABI)。发生PAD的定义为:1)下肢截肢或血运重建,或2)ABI小于0.90,随访期间ABI下降大于0.15。在事件PAD诊断之前的研究访问中注意到他汀的使用,而在检查1、访问3和访问5时测量抑郁症状。实施倾向评分匹配,以在两个治疗组的参与者之间建立平衡,即,他汀类药物治疗和他汀类药物未治疗组可通过适应症减少混杂问题。使用多变量逻辑回归模型计算倾向评分以估计接受他汀类药物治疗的概率。我们使用Cox比例风险回归来调查时间依赖性他汀类药物使用以及其他危险因素与PAD事件之间的关系。总体上按1)种族分层,2)抑郁状态,和3)年龄结果:共有4,210名参与者被纳入最终匹配的分析队列。有810(19.3%)的PAD事件发生在平均(平均)11.3(SD=5.7)年的随访时间内。在他汀类药物治疗组中,平均随访时间12.5年(SD=5.6)。发生PAD的281例(13.4%),平均随访时间为10.1(SD=5.5),而在他汀类药物未经治疗的组中,531例(25.2%)(p<0.001)。结果表明,在18.5年内,他汀类药物治疗组发生PAD事件的风险低于未治疗组(风险比[HR]0.45,95%置信区间[CI]0.33-0.62)。1)抑郁和2)种族与他汀类药物用于事件PAD之间的相互作用不显着。然而,其他显著的风险因素包括美国黑人种族,与非西班牙裔白人相比,PAD的风险降低约30%(HR=0.70,95%CI:0.58-0.84);年龄分层模型也被拟合,和染色使用仍然是45-54岁的重要治疗因素(HR0.45,95%CI:0.33-0.63),55-64(HR0.61,95%CI0.46-0.79),和65-74年(HR0.61,95%CI:0.48-0.78),但不是75-84年。
结论:75岁以下人群使用他汀类药物与PAD事件风险降低相关。种族和抑郁症都没有显着改变他汀类药物使用与PAD事件之间的关系,但是在黑人美国人中,PAD事件的风险较低。这些发现强调,对于75岁以上的人来说,他汀类药物的益处可能会减弱。研究结果还表明,抑郁症患者使用他汀类药物可能不会受到影响。
BACKGROUND: Peripheral artery disease (PAD) is associated with high morbidity and mortality and has been commonly described as a coronary heart disease equivalent. Statin medications are recommended for primary prevention of atherosclerotic cardiovascular disease (CVD) among other indications. Therefore, understanding the longitudinal relationship of incident PAD is necessary to inform future research on how to prevent the disease. Depression complicates CVD patients\' ability to properly adhere to their medications, yet the effect of depression on the relationship between statin use and incident PAD is understudied. People with PAD have a higher incidence of depressive symptoms than people without PAD. Black American and Hispanic populations are disproportionately affected by both PAD and depression yet research on the modifying effect of either race or depression on the relationship between statin use and onset of PAD is minimal. While statin utilization is highest for ages 75-84 years, there is minimal evidence of favorable risk-benefit balance. Consequently, in this project, we examined the relationship between statin use and incident PAD and whether this relationship is modified by race/ethnicity, depressive symptoms, or age.
METHODS: We used data on participants from the Multi-Ethnic Study of Atherosclerosis from visit 1 (2000) through study visit 6 (2020) who had three separate measurements of the ankle-brachial index (ABI) taken at visit 1, visit 3, and visit 5. Incident PAD was defined as 1) incident lower extremity amputation or revascularization or 2) ABI less than 0.90 coupled with ABI decrease greater than 0.15 over the follow-up period. Statin use was noted on the study visit prior to incident PAD diagnosis while depressive symptoms were measured at exam 1, visit 3, and visit 5. Propensity score matching was implemented to create balance between the participants in the two treatment groups, that is, statin-treated and statin-untreated groups, to reduce the problem of confounding by indication. Propensity scores were calculated using multivariate logistic regression model to estimate the probability of receiving statin treatment. We used Cox proportional hazards regression to investigate the relationship between time-dependent statin use as well as other risk factors with incident PAD, overall and stratified by 1) race, 2) depression status, and 3) age.
RESULTS: A total of 4,210 participants were included in the final matched analytic cohort. There were 810 incident cases (19.3%) of PAD that occurred over an average (mean) of 11.3 years (SD = 5.7) of follow-up time. In the statin-treated group, and with an average follow-up time of 12.5 years (SD = 5.6), there were 281 cases (13.4%) of incident PAD with the average follow-up time of 10.1 years (SD = 5.5), whereas in the statin-untreated group, there were 531 cases (25.2%) (P < 0.001). Results demonstrate a lower risk of PAD event in the statin-treated group compared to the untreated group (hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.33-0.62) over the span of 18.5 years. The interactions between 1) depression and 2) race with statin use for incident PAD were not significant. However, other risk factors which were significant included Black American race that had approximately 30% lower hazard of PAD compared to non-Hispanic White (HR = 0.70, 95% CI: 0.58-0.84); age-stratified models were also fitted, and stain use was still a significant treatment factor for ages 45-54 (HR = 0.45, 95% CI: 0.33-0.63), 55-64 (HR = 0.61, 95% CI: 0.46-0.79), and 65-74 years (HR = 0.61, 95% CI: 0.48-0.78) but not for ages 75-84 years.
CONCLUSIONS: Statin use was associated with a decreased risk of incident PAD for those under the age of 75 years. Neither race nor depression significantly modified the relationship between statin use and incident PAD; however, the risk of incident PAD was lower among Black Americans. These findings highlight that the benefit of statin may wane for those over the age of 75 years. Findings also suggest that statin use may not be compromised in those living with depression.