Background

Until recently, most patients with diabetes worldwide have been diagnosed when symptomatic and have high cardiovascular risk, meaning most should be prescribed cardiovascular preventive medications. However, in New Zealand, a world-first national programme led to approximately 90% of eligible adults being screened for diabetes by 2016, up from 50% in 2012, identifying many asymptomatic patients with recent-onset diabetes. We hypothesised that cardiovascular risk prediction equations derived before widespread screening would now significantly overestimate risk in screen-detected patients.

Methods

New Zealanders aged 30–74 years with type 2 diabetes and without known cardiovascular disease, heart failure, or substantial renal impairment were identified from the 400 000-person PREDICT primary care cohort study between Oct 27, 2004, and Dec 30, 2016, covering the period before and after widespread screening. Sex-specific equations estimating 5-year risk of cardiovascular disease were developed using Cox regression models, with 18 prespecified predictors, including diabetes-related and renal function measures. Equation performance was compared with an equivalent equation derived in the New Zealand Diabetes Cohort Study (NZDCS), which recruited between 2000 and 2006, before widespread screening.

Findings

46 652 participants were included in the PREDICT-1° Diabetes subcohort, of whom 4114 experienced first cardiovascular events during follow-up (median 5·2 years, IQR 3·3–7·4). 14 829 (31·8%) were not taking oral hypoglycaemic medications or insulin at baseline. Median 5-year cardiovascular risk estimated by the new equations was 4·0% (IQR 2·3–6·8) in women and 7·1% (4·5–11·2) in men. The older NZDCS equation overestimated median cardiovascular risk by three times in women (median 14·2% [9·7–20·0]) and two times in men (17·1% [4·5–20·0]). Model and discrimination performance measures for PREDICT-1° Diabetse equations were also significantly better than for the NZDCS equation (eg, for women: R²=32% [95% CI 29–34], Harrell's C=0·73 [0·72–0·74], Royston's D=1·410 [1·330–1·490] vs R²=24% [21–26], C=0·69 [0·67–0·70], and D=1·147 [1·107–1·187]).

Interpretation

International treatment guidelines still consider most people with diabetes to be at high cardiovascular risk; however, we show that recent widespread diabetes screening has radically changed the cardiovascular risk profile of people with diabetes in New Zealand. Many of these patients have normal renal function, are not dispensed glucose-lowering medications, and have low cardiovascular risk. These findings have clear international implications as increased diabetes screening is inevitable due to increasing obesity, simpler screening tests, and the introduction of new-generation glucose-lowering medications that prevent cardiovascular events. Cardiovascular risk prediction equations derived from contemporary diabetes populations, with multiple diabetes-related and renal function predictors, will be required to better differentiate between low-risk and high-risk patients in this increasingly heterogeneous population and to inform appropriate non-pharmacological management and cost-effective targeting of expensive new medications.

Funding

Health Research Council of New Zealand, Heart Foundation of New Zealand, and Healthier Lives National Science Challenge.

中文翻译：

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广泛筛查前后 2 型糖尿病的心血管风险预测：推导和验证研究

背景

直到最近，全世界大多数糖尿病患者在出现症状并具有高心血管风险时才被诊断出来，这意味着大多数人应该服用心血管预防药物。然而，在新西兰，一项世界首创的国家计划导致到 2016 年大约 90% 的符合条件的成年人接受了糖尿病筛查，高于 2012 年的 50%，确定了许多新发糖尿病的无症状患者。我们假设在广泛筛查之前得出的心血管风险预测方程现在会显着高估筛查检测到的患者的风险。

方法

从 2004 年 10 月 27 日至 2016 年 12 月 30 日的 400 000 人 PREDICT 初级保健队列研究中，确定了年龄在 30-74 岁的新西兰患有 2 型糖尿病，并且没有已知的心血管疾病、心力衰竭或严重肾功能损害，涵盖广泛筛查前后的时期。使用 Cox 回归模型开发了估计 5 年心血管疾病风险的性别特异性方程，其中包含 18 个预先指定的预测因子，包括糖尿病相关和肾功能测量。方程性能与新西兰糖尿病队列研究 (NZDCS) 中得出的等效方程进行了比较，该研究在 2000 年至 2006 年之间招募，然后进行了广泛筛选。

发现

46652 名参与者被纳入 PREDICT-1° 糖尿病亚组，其中 4114 人在随访期间经历了首次心血管事件（中位数 5·2 年，IQR 3·3-7·4）。14 829 (31·8%) 在基线时未服用口服降糖药或胰岛素。新方程估计的中位 5 年心血管风险在女性中为 4·0% (IQR 2·3-6·8)，在男性中为 7·1% (4·5-11·2)。较旧的 NZDCS 方程将女性心血管风险的中位数高估了 3 倍（中位数 14·2% [9·7-20·0]），男性高估了 2 倍（17·1% [4·5-20·0]）。PREDICT-1° 糖尿病方程的模型和判别性能测量也显着优于 NZDCS 方程（例如，对于女性：R ² =32% [95% CI 29-34]，Harrell's C =0·73 [0· 72–0·74]，罗伊斯顿的D=1·410 [1·330–1·490] vs R ² =24% [21–26], C =0·69 [0·67–0·70], D =1·147 [1·107 –1·187]）。

解释

国际治疗指南仍然认为大多数糖尿病患者的心血管风险很高；然而，我们表明，最近广泛的糖尿病筛查从根本上改变了新西兰糖尿病患者的心血管风险状况。其中许多患者的肾功能正常，未分配降糖药物，心血管风险较低。这些发现具有明显的国际意义，因为肥胖的增加、筛查测试的简化以及预防心血管事件的新一代降糖药物的引入不可避免地增加了糖尿病筛查。源自当代糖尿病人群的心血管风险预测方程，具有多种糖尿病相关和肾功能预测因子，

资金

新西兰健康研究委员会、新西兰心脏基金会和更健康的生活国家科学挑战赛。