Personalized prediction of lifetime benefits with statin therapy for asymptomatic individuals: a modeling study.
Personalized prediction of lifetime benefits with statin therapy for asymptomatic individuals: a modeling study.
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DOI：
10.1371/journal.pmed.1001361
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发表时间：
2012
期刊：
影响因子：
15.8
通讯作者：
Hunink MG
中科院分区：
文献类型：
--
作者：
Ferket BS;van Kempen BJ;Heeringa J;Spronk S;Fleischmann KE;Nijhuis RL;Hofman A;Steyerberg EW;Hunink MG
在一项由Myriam Hunink及其同事进行的建模研究中，鹿特丹的一项基于人群的队列研究用于预测他汀类药物治疗在个性化基础上可能带来的终身益处。医生需要告知无症状患者他汀类药物治疗对心血管疾病（CVD）一级预防的个性化结果。然而，目前的预测模型侧重于短期结果，而忽略了其他原因导致的死亡风险。我们的目的是在考虑竞争风险的情况下，预测他汀类药物治疗的潜在终身获益。一个基于5年随访数据的微观模拟模型来自鹿特丹研究，这是一个基于人群的队列，年龄在55岁及以上，居住在荷兰鹿特丹的Ommoord区，用于估计接受和不接受他汀类药物治疗的终生结果。使用10年随访数据对模型进行样本内验证。我们使用基线变量和模型输出来构建(1)一个基于网络的总预期寿命和无心血管疾病预期寿命增加的计算器，(2)将这些增加与系统冠状动脉风险评估（SCORE）图表进行比较的彩色图表。在2428名参与者中（平均年龄67.7岁，男性占35.5%），他汀类药物治疗使总预期寿命增加0.3年（SD 0.2），使无心血管疾病预期寿命增加0.7年（SD 0.4）。年龄、性别、吸烟、血压、高血压、血脂、糖尿病、血糖、体重指数、腰臀比和肌酐都包括在计算器中。在多变量调整后，总预期寿命和无cvd预期寿命随着血压、不利的脂质水平和体重指数的增加而增加。随着年龄的增长，获益显著下降，而sco10 -y CVD死亡风险随着年龄的增长而增加。25%的低SCORE风险参与者在无cvd预期寿命方面的获益与高SCORE风险参与者的中位数获益相同或更大。我们开发了一些工具来预测他汀类药物治疗对总寿命和无心血管疾病预期寿命的个性化增加。我们发现预测的收益很小。如果基础模型在独立队列中得到验证，这些工具可能有助于与患者讨论他汀类药物治疗的个体结果。心血管疾病（CVD）影响心脏和/或血管，是世界范围内疾病和死亡的主要原因。例如，在美国，冠心病是导致死亡的主要原因，而中风是导致大脑血液供应中断的第四大原因。冠心病是由于脂肪沉积导致心脏血管变窄，最终导致心脏血液供应减慢，并可能导致心脏病发作。已知的心血管疾病的危险因素包括吸烟、高血压、肥胖和血液中低密度脂蛋白（“坏胆固醇”）的高水平。由于许多这些危险因素可以通过改变生活方式和药物来改变，心血管疾病是可以预防的。因此，医生可以使用CVD预测模型（考虑到个体暴露的CVD危险因素的方程）来评估健康个体患CVD的风险，然后可以建议改变生活方式和药物来降低个体的CVD风险。目前的指南建议无症状（健康）的心血管疾病风险高的个体应鼓励服用他汀类降胆固醇药物作为预防措施。他汀类药物有助于预防心血管疾病的高风险健康人，但是，像所有药物一样，他们有一些不想要的副作用，所以重要的是，医生可以向患者传达他汀类药物的优点和缺点，让他们在知情的情况下做出服用这些药物的决定。告诉病人他汀类药物会降低他或她患心血管疾病的短期风险并不总是有帮助的——病人真的需要知道他汀类药物治疗的潜在终身益处。也就是说，他们需要知道如果服用他汀类药物，他们可以活多久。在这里，研究人员使用一个数学模型来预测他汀类药物治疗对没有心血管疾病史的个体的个性化终身获益（增加总寿命和无心血管疾病预期寿命）。研究人员使用鹿特丹缺血性心脏病和中风计算机模拟（RISC）模型，该模型通过六种健康状态模拟个体的生命过程，从良好到CVD或非CVD死亡，来估计健康老年人人群中接受和不接受他汀类药物治疗的终生结果。然后，他们利用这些结果和基线风险因素的信息开发了一个基于网络的计算器，适用于在常规临床实践中对他汀类药物终生获益的个性化预测。该模型估计，他汀类药物治疗使研究人群的平均预期寿命增加了0.3年，平均无cvd预期寿命增加了0.7年。与他汀类药物治疗相关的总预期寿命和无cvd预期寿命随着血压、不利胆固醇水平和体重指数（体脂指标）的增加而增加，但随着年龄的增长而下降。值得注意的是，基于网络的计算器预测，一些10年心血管疾病风险较低的个体在接受他汀类药物治疗后，其无心血管疾病预期寿命的延长可能与一些10年心血管疾病风险较高的个体相似或更大。因此，例如，一个55岁的不吸烟女性，10年心血管疾病死亡率为2%（10年内死于心血管疾病的几率为百分之二），一个65岁的男性吸烟者，10年心血管疾病死亡率为15%，他汀类药物治疗后，他们都可能获得一年的无心血管疾病预期寿命。这些发现表明，在健康个体中，他汀类药物治疗可导致总体预期寿命的平均小幅增加，而无心血管疾病预期寿命的增加略大，并表明预期寿命的益处可以通过个体的风险因素概况来预测。这些发现的准确性和普遍性受到模型中包含的假设（特别是，该模型不考虑他汀类药物治疗的已知副作用）和输入的数据的限制——重要的是，风险预测模型需要使用独立的数据集进行验证。如果未来的研究证实了这项研究的发现，研究人员基于网络的计算器可以为目前推荐的10年心血管疾病死亡率风险评估提供补充信息。然而，个性化结果的交流是否最终会导致更好的临床结果仍有待观察，因为当提供更多关于他汀类药物可能益处的信息时，患者可能不太可能选择他汀类药物治疗。请通过本摘要的在线版本（http://dx.doi.org/10.1371/journal.pmed.1001361）访问这些网站。美国心脏协会为患者、护理人员和专业人员提供了关于多种心血管疾病的信息。包括关于胆固醇药物治疗和心脏病发作风险计算器的信息英国国家健康服务选择网站提供了关于心血管疾病和他汀类药物的信息英国心脏基金会提供了关于心脏病和保持心脏健康的信息；关于他汀类药物的信息也可获得，包括决定服用他汀类药物的个人故事美国国家心肺和血液研究所提供了广泛的心血管疾病信息，欧洲心脏病学会心血管疾病风险评估模型（SCORE）可用。MedlinePlus提供了关于心脏病、血管疾病、中风和他汀类药物的许多其他信息来源的链接（英语和西班牙语）。
In a modeling study conducted by Myriam Hunink and colleagues, a population-based cohort from Rotterdam is used to predict the possible lifetime benefits of statin therapy, on a personalized basis. Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy. Please see later in the article for the Editors' Summary Cardiovascular disease (CVD) affects the heart and/or the blood vessels and is a major cause of illness and death worldwide. In the US, for example, coronary heart disease—a CVD in which narrowing of the heart's blood vessels by fatty deposits slows the blood supply to the heart and may eventually cause a heart attack—is the leading cause of death, and stroke—a CVD in which the brain's blood supply is interrupted—is the fourth leading cause of death. Established risk factors for CVD include smoking, high blood pressure, obesity, and high blood levels of a fat called low-density lipoprotein (“bad cholesterol”). Because many of these risk factors can be modified by lifestyle changes and by drugs, CVD can be prevented. Thus, physicians can assess a healthy individual's risk of developing CVD using a CVD prediction model (equations that take into account the CVD risk factors to which the individual is exposed) and can then recommend lifestyle changes and medications to reduce that individual's CVD risk. Current guidelines recommend that asymptomatic (healthy) individuals whose likely CVD risk is high should be encouraged to take statins—cholesterol-lowering drugs—as a preventative measure. Statins help to prevent CVD in healthy people with a high predicted risk of CVD, but, like all medicines, they have some unwanted side effects, so it is important that physicians can communicate both the benefits and drawbacks of statins to their patients in a way that allows them to make an informed decision about taking these drugs. Telling a patient that statins will reduce his or her short-term risk of CVD is not always helpful—patients really need to know the potential lifetime benefits of statin therapy. That is, they need to know how much longer they might live if they take statins. Here, the researchers use a mathematical model to predict the personalized lifetime benefits (increased total and CVD-free life expectancy) of statin therapy for individuals without a history of CVD. The researchers used the Rotterdam Ischemic Heart Disease & Stroke Computer Simulation (RISC) model, which simulates the life courses of individuals through six health states, from well through to CVD or non-CVD death, to estimate lifetime outcomes with and without statin therapy in a population of healthy elderly individuals. They then used these outcomes and information on baseline risk factors to develop a web-based calculator suitable for personalized prediction of the lifetime benefits of statins in routine clinical practice. The model estimated that statin therapy increases average life expectancy in the study population by 0.3 years and average CVD-free life expectancy by 0.7 years. The gains in total and CVD-free life expectancy associated with statin therapy increased with blood pressure, unfavorable cholesterol levels, and body mass index (an indicator of body fat) but decreased with age. Notably, the web-based calculator predicted that some individuals with a low ten-year CVD risk might achieve a similar or larger gain in CVD-free life expectancy with statin therapy than some individuals with a high ten-year risk. So, for example, both a 55-year-old non-smoking woman with a ten-year CVD mortality risk of 2% (a two in a hundred chance of dying of CVD within ten years) and a 65-year-old male smoker with a ten-year CVD mortality risk of 15% might both gain one year of CVD-free life expectancy with statin therapy. These findings suggest that statin therapy can lead on average to small gains in total life expectancy and slightly larger gains in CVD-free life expectancy among healthy individuals, and show that life expectancy benefits can be predicted using an individual's risk factor profile. The accuracy and generalizability of these findings is limited by the assumptions included in the model (in particular, the model did not allow for the known side effects of statin therapy) and by the data fed into it—importantly, the risk prediction model needs to be validated using an independent dataset. If future research confirms the findings of this study, the researchers' web-based calculator could provide complementary information to the currently recommended ten-year CVD mortality risk assessment. Whether communication of personalized outcomes will ultimately result in better clinical outcomes remains to be seen, however, because patients may be less likely to choose statin therapy when provided with more information about its likely benefits. Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001361. The web-based calculator for personalized prediction of lifetime benefits with statin therapy is available (after agreement to software license) The American Heart Association provides information about many types of cardiovascular disease for patients, carers, and professionals, including information about drug therapy for cholesterol and a heart attack risk calculator The UK National Health Service Choices website provides information about cardiovascular disease and about statins Information is available from the British Heart Foundation on heart disease and keeping the heart healthy; information is also available on statins, including personal stories about deciding to take statins The US National Heart Lung and Blood Institute provides information on a wide range of cardiovascular diseases The European Society of Cardiology's cardiovascular disease risk assessment model (SCORE) is available MedlinePlus provides links to many other sources of information on heart diseases, vascular diseases, stroke, and statins (in English and Spanish)
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影响因子：
168.9
作者：
Jackson, R;Lawes, CMM;Rodgers, A
通讯作者：
Rodgers, A
影响因子：
--
作者：
Halvorsen, PA;Kristiansen, IS
通讯作者：
Kristiansen, IS
影响因子：
39.2
作者：
Glynn RJ;Koenig W;Nordestgaard BG;Shepherd J;Ridker PM
通讯作者：
Ridker PM
DOI：
10.1136/bmj.c6624
发表时间：
2010-12-09
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Hippisley-Cox J;Coupland C;Robson J;Brindle P
通讯作者：
Brindle P
影响因子：
37.8
作者：
Lazar, Lawrence D.;Pletcher, Mark J.;Goldman, Lee
通讯作者：
Goldman, Lee