心血管與腎臟代謝健康:風險評估的關鍵指南

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美國心臟協會最近提出了PREVENT風險預測方程式,旨在改善心血管疾病(CVD)的絕對風險評估。這些性別特異且無種族歧視的方程式,整合了腎功能與社會健康因素,能夠為30至79歲的成年人提供10年及30年的CVD風險預估,並有助於為不同階段的心血管-腎臟-代謝綜合徵患者提供更具針對性的預防策略。

Novel Prediction Equations for Absolute Risk Assessment of Total Cardiovascular Disease Incorporating Cardiovascular-Kidney-Metabolic Health: A Scientific Statement From the American Heart Association

納入心血管-腎臟-代謝健康的總心血管疾病絕對風險評估新預測方程式:美國心臟協會的科學聲明

Khan SS, Coresh J, Pencina MJ, et al. Novel Prediction Equations for Absolute Risk Assessment of Total Cardiovascular Disease Incorporating Cardiovascular-Kidney-Metabolic Health: A Scientific Statement From the American Heart Association. Circulation. 2023;148(24):1982-2004. doi:10.1161/CIR.0000000000001191

https://pubmed.ncbi.nlm.nih.gov/37947094/

Abstract

Cardiovascular-kidney-metabolic (CKM) syndrome is a novel construct recently defined by the American Heart Association in response to the high prevalence of metabolic and kidney disease. Epidemiological data demonstrate higher absolute risk of both atherosclerotic cardiovascular disease (CVD) and heart failure as an individual progresses from CKM stage 0 to stage 3, but optimal strategies for risk assessment need to be refined. Absolute risk assessment with the goal to match type and intensity of interventions with predicted risk and expected treatment benefit remains the cornerstone of primary prevention. Given the growing number of therapies in our armamentarium that simultaneously address all 3 CKM axes, novel risk prediction equations are needed that incorporate predictors and outcomes relevant to the CKM context. This should also include social determinants of health, which are key upstream drivers of CVD, to more equitably estimate and address risk. This scientific statement summarizes the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: PREVENT (AHA Predicting Risk of CVD Events). The PREVENT equations enable 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure), include estimated glomerular filtration rate as a predictor, and adjust for competing risk of non-CVD death among adults 30 to 79 years of age. Additional models accommodate enhanced predictive utility with the addition of CKM factors when clinically indicated for measurement (urine albumin-to-creatinine ratio and hemoglobin A1c) or social determinants of health (social deprivation index) when available. Approaches to implement risk-based prevention using PREVENT across various settings are discussed.

摘要

心血管-腎臟-代謝(CKM)綜合症是一個新概念,最近由美國心臟協會定義,以回應代謝和腎臟疾病的高盛行率。流行病學數據顯示,隨著個體從CKM階段0進展到階段3,動脈粥樣硬化性心血管疾病(CVD)和心衰竭的絕對風險均提高,但風險評估的最佳策略需要進一步完善。以匹配干預措施的類型和強度與預測風險及預期治療效益為目標的絕對風險評估,仍然是主要預防的基石。考慮到越來越多的療法可以同時針對所有三個CKM軸,亟需新型風險預測方程式,納入與CKM情境相關的預測因子和結果。這還應包括健康的社會決定因素,這是心血管疾病的關鍵上游驅動因素,以更公平地估算和應對風險。該科學聲明總結了新開發的性別特定、無種族風險方程式的背景、理由和臨床意涵:PREVENT(美國心臟協會心血管事件風險預測)。PREVENT方程式可提供總心血管疾病(動脈粥樣硬化性心血管疾病和心衰竭的綜合)的10年和30年風險估算,並將估計的腎小管濾過率作為預測因子,並調整30至79歲成人的非心血管死亡競爭風險。其他模型在臨床需要時,通過增加CKM因子(尿液白蛋白與肌酐比率和糖化血紅蛋白)或社會決定因素(社會剝奪指數)來增強預測效用。討論了如何在各種環境中實施基於風險的預防策略,使用PREVENT。

肥胖、糖尿病和慢性腎病(CKD)都與心血管疾病(CVD)的高發病率和死亡率負擔密切相關;這些疾病常常共存,並且不成比例地影響弱勢群體(例如,代表性不足的種族和族裔群體)。考慮到這些慢性病之間的複雜相互作用,需要一個全面的心血管疾病預防方法,概念上和治療上整合肥胖、糖尿病和CKD的預防與管理。因此,美國心臟協會(AHA)最近制定了一個共識定義,將心血管-腎臟-代謝(CKM)綜合症定義為一種系統性疾病,涵蓋那些有CVD風險或已存在CVD的人。

在定義CKM概念時,CKM健康科學諮詢小組(SAG)強調了需要採取反映CKM綜合症進展性病理生理學的預防方法,以及隨著CKM綜合症的發展,絕對CVD風險逐步增加的必要性。因此,CKM綜合症被定義為一個分期結構,從階段0開始,代表沒有CKM風險因子;階段1,過多或功能失調的脂肪組織;階段2,代謝風險因子或中度至高風險的慢性腎病;階段3,CKM中的亞臨床CVD,或亞臨床CVD的風險等價(高風險CKD或高預測CVD風險);階段4,伴隨CKM風險因子的臨床CVD。需要注意的是,CKM分期路徑是雙向的,允許個體在CKM階段之間進行進展或退步。這一點尤其重要,突顯了CKM病症可能緩解的潛力(例如,恢復胰島素敏感性至理想血糖狀態、正常化血壓),甚至可以回到階段0,通過針對性的預防干預(例如,促進理想心血管健康的健康行為干預)。

CKM階段強調了過多和功能失調的脂肪組織作為關鍵病理生理機制的中心角色。這提供了早期識別疾病進程中個體的機會,以促進在發展為明顯臨床CVD(階段4)之前的預防工作。然而,並非所有具有階段2風險因子(例如,高血壓、糖尿病、CKD)的人都會有前期的過多或功能失調的脂肪組織。考慮到無論原因如何,高血壓、糖尿病和CKD的風險意義和治療策略相似,階段2定義為存在這些情況,無論是否伴隨過多或功能失調的脂肪組織。

CKM框架的核心是強調在CKM階段0到3中基於風險的心血管疾病初級預防,該框架整合了定性(CKM階段)和定量(多變量風險評估)方法。雖然基於風險的預防已經是心血管疾病預防的基石超過20年,但識別出CKM人群中有待滿足的心血管疾病風險評估和預防需求的機會。正如CKM健康總統諮詢中詳細說明的,針對這一背景的心血管疾病風險評估需要新的風險預測算法,以公平地改善個體和群體層面的CKM健康,並以生命週期的視角看待。

CKM健康小組由AHA任命,要求開發或推薦一種定量方法,以進行心血管疾病的絕對風險評估,這可以用來進一步指導護理,並補充定義CKM綜合症的定性分級系統。CKM健康小組內的預測工作組首先評估了有關事件心血管疾病(及其亞類型)的風險評估的科學證據,確定了現有多變量風險預測方程式中的缺口,隨後開發了一系列新的風險預測方程式。

本科學聲明的目的是批判性地回顧可用證據,以支持PREVENT方程式(美國心臟協會心血管事件風險預測)的合理性和開發。PREVENT旨在使用臨床醫生容易獲得的數據來估算心血管疾病的絕對風險,以便在日常臨床實踐中輕鬆實施。在此,我們強調新開發的性別特定、無種族風險預測方程式的概念和方法學進展,這些方程式估算短期和長期風險,將腎功能納入常規心血管疾病風險評估,允許額外考慮以CKM為重點的臨床變量和社會健康決定因素(SDOH)指標,並將心衰竭(HF)和動脈粥樣硬化性心血管疾病(ASCVD)納入總心血管疾病結果,並調整非心血管死亡的競爭風險。我們提供了關於未來在臨床和社區基礎設施中推廣和實施PREVENT的考量,重點在於醫生與患者之間的風險溝通和共同決策。

對於這些風險預測方程式的目的,我們首先針對一般人群的初級預防(即預防首次心血管事件)進行了目標聚焦,應用於沒有基線心血管疾病的典型成年人。圖1顯示了整體框架,概述了關鍵目標,包括以下幾點:(1)篩查CKM風險,(2)評估CVD風險,(3)確定CKM階段,和(4)降低CKM風險。值得注意的是,這並不涉及或減輕對於那些已存在CVD(例如,二級預防、心房顫動中的中風預防)、有CVD相關症狀(例如,胸痛)或某些富含遺傳風險的患者亞群(例如,家族性高脂血症、肥厚型心肌病)的風險評估和預防的重要性,因為這些超出了此風險預測計劃的範疇,需要不同的臨床算法。

圖1. 心血管疾病風險基礎預防的概念框架,整合了使用PREVENT進行的風險評估與心血管-腎臟-代謝健康分級。

ASCVD 代表動脈粥樣硬化性心血管疾病;CKM,心血管-腎臟-代謝;CVD,心血管疾病;GLP-1RA,胰高血糖素樣肽-1受體激動劑;HbA1c,糖化血紅蛋白;HF,心衰竭;PREVENT,美國心臟協會心血管事件風險預測;SDOH,社會健康決定因素;SGLT2i,鈉-葡萄糖共轉運蛋白2抑制劑;UACR,尿液白蛋白與肌酐比率。

現有的CVD預測方程式

自1996年舉行的第27屆貝塞斯達會議以來,將針對心血管疾病(CVD)的傳統或因果風險因素的預防干預強度與患者的絕對風險相匹配的概念,已成為CVD預防的範式。因此,多變量風險預測方程式應運而生,並成為臨床預防策略的基石,隨著所包含的群體、預測因子和結果的技術細節的演變,這些內容在2013年《心血管風險評估報告》中進行了詳細的回顧。簡而言之,國家膽固醇教育計畫專家小組的第三份報告推薦使用Framingham 10年風險評分(Framingham Risk Score)來評估冠心病(CHD)風險。然而,該模型是基於一個僅由白人組成的地理限制樣本中推導出的,只預測冠心病,並未將糖尿病納入預測因子。

因此,在2013年,美國心臟學會(ACC)/美國心臟協會(AHA)聯合隊列方程式(PCEs)提供了一種修訂的風險評估方法,這在以下幾個方面取得了重要進展:(1)將中風納入ASCVD的綜合結局,(2)納入黑人成年人,以及(3)將糖尿病作為風險因子納入,而非假設它是風險等價。PCEs是性別和種族特定的方程式,來源於五個社區基礎的隊列(ARIC [社區動脈粥樣硬化風險]; CHS [心血管健康研究]; CARDIA [年輕成年人冠狀動脈風險發展]; FHS [Framingham心臟研究]; FOS [Framingham後裔研究]),包含了11240名白人女性、9098名白人男性、2641名黑人女性和1647名黑人男性的數據,年齡在40至79歲之間,且無冠心病(定義為心肌梗死[已知或未知]、經皮冠狀動脈介入、冠狀動脈搭橋手術)、中風、心衰竭或心房顫動的病史。

2013年的風險評估指導方針與血膽固醇管理建議相結合,優先考慮絕對CVD風險評估,以指導醫生和患者之間的討論,考慮治療。更新或新的膽固醇管理指導方針(2018)、血壓(2017)和心血管疾病的初級預防(2019)都重申並完善了對風險預測、使用PCE進行風險評估和基於風險的預防的建議。此外,最新的心衰竭管理指導方針(2022)建議考慮使用生物標誌物(例如,類納肽,如B型類納肽)或多變量風險模型來估算絕對風險(例如,PCP-HF [預防心衰竭的聯合隊列方程式]),但並未推薦具體的風險預測模型。當前AHA/ACC指導方針基於多變量風險評估的建議的集中總結詳見表1。此外,美國糖尿病協會2023年護理標準認可在糖尿病患者中使用PCE評估ASCVD風險。

表1. 當前AHA/ACC指導方針中關於多變量風險評估和基於風險的心血管疾病預防的建議總結

開發新風險預測方程式的理由

總體概述

2013年的美國心臟學會(ACC)/美國心臟協會(AHA)聯合隊列方程式(PCEs)在指導方針中被廣泛引用,如前面部分所述,並在外部數據集中得到了廣泛驗證,並在臨床護理中得到廣泛應用。隨著風險因素(例如,煙草使用)的流行病學變化、風險因素水平的世俗趨勢(例如,過去十年中脂質水平的下降)、護理模式的變化(例如,各種降壓治療的更廣泛使用),使用PCEs可能會高估新發生的動脈粥樣硬化性心血管疾病(ASCVD)風險。因此,CKM健康科學顧問小組(SAG)同意現在是時候修訂和更新風險方程式,以解決PCEs和其他現有模型在風險預測方面的幾個關鍵差距。儘管考慮過機器學習方法並對其在CVD風險預測中的應用進行了評估,但決定不使用這些方法,因為當前模型開發的重點在於已知風險因素、風險梯度和年齡特異性交互作用。在這個背景下,回歸技術與機器學習方法表現相當,並且能夠直接提供每個風險因素與後續風險之間的關聯強度。這使得模型開發採用了一種簡約的方法,並可能增強在臨床實踐中的應用。未來,如果需要包括多個風險因素和未知交互作用的模型開發,則可以考慮使用機器學習方法。

電子病歷數據源的可用性

自2009年只有12%的醫院擁有電子病歷(EMR)系統以來,EMR的使用大幅增加,現在近96%的非聯邦急性護理醫院和近80%的辦公室基礎醫生擁有經認證的EMR系統。隨著EMR在臨床健康系統中幾乎無處不在,訪問真實的臨床數據以生成現代、可普遍適用的臨床相關和多樣化人群樣本現在變得可能。EMR數據已在科學出版物中廣泛應用,用於檢查流行病學、指導方針建議中的實施差距和風險預測,並提供可靠有效的估計。鑒於這些數據集的固有規模更大,擁有來自不同種族、民族、社會經濟和地理背景的數百萬人可供模型開發,其使用預期將提高CVD風險估計的普遍性。在模型推導和驗證數據集中使用多樣化樣本將確保用於推導模型的研究人群與其應用的對象(例如,接受臨床護理的一般人群)相匹配。

然而,使用電子健康記錄數據也存在挑戰和限制。一項最近的系統評估概述了使用EMR數據的主要問題,包括有限的多中心數據使用、關鍵變量的缺失和非標準化測量、缺乏跨地點的驗證和失訪。另一項系統評估比較了數據集類型,顯示EMR數據的預測效用優於行政數據,但指出大多數研究未能包括社會經濟預測因子或模型校準的度量,且未考慮臨床影響。隨著可用數據源(例如“All of Us”、“英國生物銀行”)的增長,EMR數據在這些應用中的使用只會繼續增長。工作組考慮了所有可用數據源,並審查了每個數據源的優勢和挑戰,認為將EMR數據納入推導和驗證數據集將是高度創新的,並在總體上增強新開發風險預測方程式的預測效用和普遍性。

動脈粥樣硬化性心血管疾病的已知風險因素

已知大多數動脈粥樣硬化性心血管疾病(CVD)風險可歸因於傳統風險因素,即使在這些因素的水平輕微升高的情況下(例如,血壓升高但未達到高血壓標準)。在三項大型前瞻性研究的分析中,幾乎所有經歷非致命性冠心病(CHD)事件的人(92%的男性和87%的女性)在事件發生之前至少有一個臨床上升高的主要風險因素(定義為總膽固醇≥6.22 mmol/L或≥240 mg/dL,收縮壓≥140 mmHg,舒張壓≥90 mmHg,吸煙或糖尿病)。對於致命性冠心病事件,也觀察到了類似的估計。在VIRGO研究(早期心肌梗死患者性別對結果的影響的變異)中,18至55歲的早發心肌梗死患者的前瞻性觀察性隊列,傳統風險因素的群體歸因比例為85%。這些研究及其他研究(例如INTERHEART)強調了傳統風險因素對CVD風險評估的重要貢獻,因此需要將其納入更新的風險方程式。當可能時,將風險因素水平建模為連續預測因子也有助於識別那些在缺乏臨界值的風險因素(如高血壓、糖尿病)下,仍面臨多個風險因素(例如,血壓在前高血壓範圍內,血糖在前糖尿病範圍內)輕微升高的個體。此外,傳統風險因素在臨床實踐中也會常規測量,並且是預防治療的目標,這使得風險評估與治療干預之間相一致。雖然年齡和性別是不可改變的,但它們都是CVD風險的關鍵組成部分,也是CVD風險方程式中的重要預測因子。

健康行為,包括身體活動和飲食質量,是降低CVD風險的重要目標。這些因素此前未包含在風險預測中,因為這些因素所帶來的風險在很大程度上是通過CVD風險因素來介導的(例如,高血壓、糖尿病)。低或不健康的心肺適能(CRF),作為心血管代謝健康的綜合指標,與成人中更高的CVD和全因死亡風險相關。提高對CRF評估重要性的認識,以及CRF的可調整性和CRF與CVD、認知和心理健康的關聯,是AHA之前一份科學聲明的重點。然而,CRF評估未在臨床環境中廣泛實施,主要因為成本和擴展性,因此未能納入風險預測算法中。

動脈粥樣硬化性心血管疾病和CKM健康指標的新風險標記

然而,基於傳統CVD風險因素的風險評估不斷改進的需求,導致持續尋找可能進一步增強風險評估的新風險標記。流行病學數據支持CKM風險標記(例如,腎功能、代謝健康)與總CVD和個別CVD亞型、ASCVD和HF之間的強大關聯。越來越多的長期研究為這些因素與終生總CVD、ASCVD和HF的風險之間的聯繫提供了直接證據。除了CVD的更大負擔,數據顯示CKM健康不良的人群中CVD的發病年齡更早。在此,我們回顧CKM健康風險標記的證據及其在提高風險評估的精確性和準確性方面的效用。

CVD在慢性腎病(CKD)患者中的更高風險已被廣泛確認,這也是AHA之前一份科學聲明的重點。事實上,CKD患者死於CVD事件的可能性高於進展到腎衰竭。在CKD預後聯盟的一項分析中,包含超過900萬個體,發現每降低15 mL·min–1·1.73 m–2的預估腎小管過濾率(eGFR),ASCVD風險(調整危險比為1.30 [95% CI, 1.26–1.35])和致命性冠心病風險(1.72 [1.46–2.04])均更高,這在CKD患者(eGFR <60 mL·min–1·1.73 m–2)中與其他風險因素無關。支持將eGFR納入CVD風險預測的因素包括其常規測量和幾乎所有臨床實驗室系統提供的自動計算,以及同時針對CKD和CVD風險的新療法(例如,鈉-葡萄糖共轉運蛋白-2抑制劑、finerenone)的可用性。儘管在PCEs中評估了腎功能的測量,但在用於推導的樣本中,低eGFR的個體(例如,eGFR <30 mL·min–1·1.73 m–2的第4期CKD)較少,這導致該樣本中eGFR的預測效用有限。相比之下,PREVENT模型的開發包括了更多的腎功能受損個體,這是通過包括EMR樣本和更廣泛的研究隊列數據來實現的。

目前,建議對患有糖尿病或CKD的患者進行年檢或根據CKD風險狀態進行更頻繁的尿白蛋白-肌酐比率檢測。該檢測簡單易行,成本低廉,應定期重複以便持續監測和治療決策。此外,有充分證據表明,尿白蛋白-肌酐比率的較高水平與患有和未患有高血壓、糖尿病和CKD的人群中CVD事件的發生具有逐步、劑量依賴性關聯。在心臟結果預防評估試驗的數據中,即使在患有或未患有糖尿病的人群中,低水平的尿白蛋白(以前稱為“微白蛋白尿”)也與心肌梗死、中風或心血管死亡的風險增加有關。在CVD亞型中,較高的尿白蛋白-肌酐比率負擔也與前臨床HF(例如,心臟結構和功能的異常)和HF相關。因此,建議在CKM階段2及以上的個體中每年檢查尿白蛋白-肌酐比率。

在代表代謝健康的預測因子中,體重指數(BMI)作為例行初級護理診所訪問的一部分,易於獲得。BMI是CVD的公認風險因素,也是AHA一份單獨的科學聲明的重點。儘管BMI是HF的獨立風險因子,但BMI與ASCVD的短期關聯在很大程度上是由因果路徑中的更接近的主要CVD風險因素(例如,糖尿病、高血壓)介導的,因此將BMI納入風險預測方程式對於區分的附加效用有限。然而,當不在模型中包括BMI時,可能會導致在BMI較高的個體中較不理想的校準。一項最近的研究將8個縱向隊列(n=37,311)進行了匯總,顯示PCEs在區分(C統計量0.760)上表現良好,但在中度或重度肥胖的個體中過高估計了ASCVD風險(預估風險比率1.36)。

可用證據支持在有糖尿病和無糖尿病的個體中,血糖異常與CVD風險之間的穩固關聯。血糖異常的篩查可以通過測量血紅蛋白A1c(HbA1c)來實現,這通常在例行醫療中獲得,且是診斷糖尿病的金標準。在一項隊列研究中,HbA1c水平的輕微變化(每次下降0.1%)與全因死亡率和CVD相關死亡風險呈負相關。其他證據還表明,HbA1c水平較高與心血管結果存在劑量依賴性關聯。此外,HbA1c的預測能力可能會在目前的風險評估工具中被低估,因此考慮HbA1c水平將會增強風險評估模型的準確性。這可能尤其適用於高血壓患者,因為持續的升高的HbA1c水平在降低高血壓控制狀況的心血管預後中發揮了重要作用。因此,該指標被納入PCEs和修訂的方程式中,以提高風險估計的準確性。

最後,認知和心理健康不良因素(例如,抑鬱、焦慮和慢性壓力)也是高CVD風險的已知獨立因素,這些已經在AHA的科學聲明中得到了充分的支持。這些狀況的流行是普遍的,且可能會影響健康行為、CVD風險因素的控制和與醫療服務的互動。這些因素也在AHA的預防政策中得到了認可,儘管這些風險因子尚未納入傳統風險預測中。慢性壓力和社會孤立會引發身體對壓力的反應,增加交感神經活動,並引起內分泌變化,這可能導致更高的血壓、心率和升高的糖尿病風險。

對於這些不良因素的早期識別、評估和治療的必要性將使臨床醫生能夠更好地辨別高風險的CVD個體並制定適當的干預措施。需要對所有這些不良因素進行調查和整合,以確保其在CVD風險評估中的納入。考慮到這些因素的互動性、連續性及其對個人風險的影響,整合這些指標的努力將進一步推動向基於風險的干預治療和早期檢測的轉變。

擴展心血管疾病(CVD)結果

在美國,心血管疾病(CVD)的負擔正在增加,估計有1.28億名20歲以上的成年人受到冠心病(CHD)、中風、心力衰竭(HF)和高血壓的影響。存在顯著的差異,非西班牙裔黑人、美國印度人和阿拉斯加原住民或南亞美國人群體承受著不成比例的負擔。此外,自COVID-19疫情開始以來,因CVD導致的年齡調整死亡率已經上升。與動脈粥樣硬化性心血管疾病(ASCVD)相比,心力衰竭的死亡率上升幅度相對較大。心力衰竭也是65歲以上人群住院的主要原因,並且在所有年齡組中都有所增加。大約670萬美國成年人有心力衰竭的現患,預計到2030年,這一數字可能會增至850萬。45歲時發展成心力衰竭的終身風險估計在20%至45%之間。這些有關不利趨勢和死亡率、住院率、心力衰竭的現患和發病率的觀察,均顯示出優先考慮心力衰竭的初級預防的重要性。因此,心力衰竭的發作或首次事件在基於風險的預防中是臨床相關的終點,尤其在CKM(心腎代謝)背景下。特別是,心力衰竭是慢性腎病(CKD)患者中最主要的心血管表現。即使在控制了主要風險因素(如血糖、血壓、膽固醇、尿白蛋白和避免吸煙)時,糖尿病患者仍存在心力衰竭的殘餘或過剩風險。

首次在“2022年ACC/AHA/美國心力衰竭學會心力衰竭管理指導方針”中提出了針對心力衰竭首次事件絕對風險的多變量風險預測建議,以指導其初級預防。儘管討論了幾個可以應用的潛在工具(例如,PCP-HF,這是從與ASCVD風險的PCEs相同的隊列中導出的;Framingham心力衰竭風險評分;ARIC風險評分;健康老化與身體組成研究心力衰竭評分),但該指導方針並未推薦使用特定的風險評分。目前,數據不支持區分收縮功能減退性心力衰竭和舒張功能保留性心力衰竭的預測,因為這些無症狀個體之間存在共同的風險因素和相似的主要預防策略。高血壓是減少收縮功能性心力衰竭和保留收縮功能性心力衰竭的主要可調因素。未來的研究應評估對這些心力衰竭亞型風險進行預測的必要性,特別是在預防治療選擇可能不同且可以針對收縮功能減退性心力衰竭和舒張功能保留性心力衰竭進行量身定制時。

理解一個人發展成總CVD的絕對風險估計,包括相關的CVD亞型,對於了解總風險負擔並能指導預防策略的類型和強度至關重要。PREVENT模型提供了總CVD和每個CVD亞型(ASCVD和HF)的風險估計,因此在綜合中包含。PREVENT因此提供了一個單一的多變量風險方程,為臨床醫生提供了一個簡化的框架。PREVENT還概念性地建立在先前發表的全球CVD FHS模型之上。PREVENT方程中ASCVD和HF風險估計的高一致性(相關性≥0.9)支持將總CVD作為綜合體進行估計。預測總CVD還解決了僅專注於ASCVD而可能低估絕對風險的可能性,特別是在CKM健康不佳的人群中(如重度肥胖、糖尿病和CKD),在這些人群中,HF的風險相對於ASCVD的風險更大。

工作小組還考慮了其他與CKM相關的結果,包括其他類型的CVD(例如,臨床外周動脈疾病事件、心房顫動)、亞臨床CVD(例如,冠狀動脈鈣化)和CVD風險因素(例如,高血壓、糖尿病)。然而,外周動脈疾病和心房顫動在EMR數據集或基於研究的隊列中缺乏統一的確定性,這引起了擔憂。雖然預測非零冠狀動脈鈣化或其他亞臨床疾病標記在CVD事件罕見的年輕成年人中可能具有實用性,但依賴替代結果可能會導致誤分類。然而,亞臨床疾病的存在在CKM階段(例如,第三階段)的分類中非常重要,應進一步研究整合風險預測模型(例如,多族裔動脈粥樣硬化研究、太空人心血管健康與風險修飾計劃)。最後,對於自身風險因素的預測(例如,高血壓、糖尿病、高脂血症)被認為在青少年和年輕成年人中具有更大相關性,因為重點是原發性預防。

工作小組還考慮了其他與CKM相關的結果,如不良腎臟結果、認知障礙和癡呆,但由於病理生理和風險因素的差異,這些結果被認為超出了當前工作的範疇。未來的努力應鼓勵關注擴展所有CKM相關疾病的風險預測工作,因為這些疾病具有顯著的相關 morbidity、mortality和醫療費用。

長期風險評估

PREVENT方程能夠準確且精確地估計30至79歲成年人CVD的短期和長期風險。這些新模型採用生命週期的觀點,以年齡作為時間尺度。這將使得在更廣泛的年齡範圍內進行預防工作,並提供在年輕成年人中更早介入的機會,因為CKM風險因素的存在與CVD的早期呈現相關。雖然年輕成年人短期內CVD的絕對風險較低,導致對這一年齡範圍內風險評估的價值提出質疑,但來自全國代表性樣本的數據顯示,超過一半的低估計10年ASCVD或HF風險的成年人,實際上存在高長期風險。一般而言,年輕成年人即使在存在風險因素(如高血壓、糖尿病)水平輕微升高的情況下,其10年或短期絕對風險仍然較低,而這些風險因素被認為與高CVD終身風險相關。當單獨使用短期風險時,可能會導致那些實際上面臨高終身風險的低短期風險個體被錯誤安慰。因此,終身風險可以在生命早期進行更積極的風險因素修正,當這些策略可能帶來更大益處時,這在幾份最近的專家共識報告中已經概述,重點放在年輕成年人CVD風險的預防和治療上。

從心血管疾病風險預測方程中移除種族

工作小組討論了種族在心血管疾病(CVD)風險預測中的角色。由於種族是一個社會構造,是歷史上與各種生活經歷相關的複雜代理變量,因此在風險預測中包含種族有可能被錯誤解讀為生物學風險因素,這可能導致基於種族的治療決策。因此,事先決定在PREVENT的開發中不包括種族作為預測因子,並使用最近開發的基於血清肌酐的無種族方程(CKD-EPI 2021 [慢性腎病流行病學合作組])。這與在醫學中普遍去除種族的臨床算法的日益共識相一致。種族歧視,而非種族,構成了我們的社會和個人生活經歷,與不利的社會決定因素(SDOH)相關,並且是導致不良CVD結果的主要驅動因素。因此,許多人主張測量並納入結構性種族主義或其他SDOH(例如教育、收入、社會剝奪指數)的衡量,這些因素可能會被干預。例如,QRISK,英國的一個CVD風險預測模型,納入了基於郵政編碼的社會剝奪指數(Townsend剝奪分數)。

此外,在風險預測中納入種族可能暗示種族差異是不可改變的,並可能使種族被固化為生物學構造,這可能會加劇健康差距。在這方面,重要的是要注意到,心血管疾病的風險因素和發病率仍然存在差距,黑人個體的水平和比例均較高。因此,評估和解決構成種族差異的社會決定因素至關重要。然而,大多數當前數據集並不定期包括全面的SDOH衡量,這限制了將這些因素納入風險預測的能力。此外,應強調的是,評估種族歧視直接影響的工具和措施目前仍然有限。因此,也許最關鍵的是,需要加強研究努力,以確定導致種族差異的非生物學因素,並不斷更新和修訂風險預測模型,以增強這些衡量的評估。

在PREVENT的當前模型開發中,在可用的子集內納入了郵政編碼層級的社會剝奪指數。然而,儘管有興趣納入更直接反映與種族主義相關的風險的措施(例如,居住隔離、感知的種族歧視)及其他個人和基於地點的社會驅動因素(例如,收入、教育、居住綠地),但缺乏標準化的評估和數據來源的捕捉是一個主要限制。因此,儘管PREVENT方程代表了一個重要的進步,但社會剝奪指數的整合僅僅是第一步;未來的風險預測應優先考慮納入能夠代表個體歧視經歷、結構性和系統性種族主義的相關措施,以及基於個人和地點的SDOH。

隨著我們的進步,努力轉變護理提供以公平地改善CKM(心腎代謝)健康,我們必須承認結構性和系統性種族主義對CVD風險的影響。我們應監測可能導致在已經不太可能被適當開處方基於證據的藥物(例如,類固醇、最新的降糖藥)時系統性低估風險的潛在意外後果。因此,PREVENT在關鍵社會人口子群(例如,種族和族裔、社會剝奪指數的分層)中的校準經過仔細評估,並在黑人個體中顯示出良好的校準(基本PREVENT方程的校準斜率為1.11 [0.79–1.24])。

還需注意的是,所有風險估計均基於人口平均數,可能會低估或高估任何特定個體的風險。風險估計旨在作為指導和臨床醫生與患者討論的起點。然而,建議應針對每位患者的生活經歷和社會健康決定因素的全面評估進行個性化和情境化。在不確定的患者中,可以考慮進行序列診斷測試,若公平使用,能夠可靠地重新分類所有個體和群體的風險。

PREVENT風險方程的開發及臨床意義

如Khan等人所詳述,PREVENT模型是從46個觀察性隊列研究和電子病歷(EMR)數據集中衍生和驗證的,這些研究涵蓋了6612004名年齡在30到79歲之間的美國成年人。因此,這些新開發的性別特異性、無種族模型對目標人群具有廣泛的普遍性。PREVENT方程預測總體心血管疾病(CVD)的風險(即動脈粥樣硬化性心血管疾病(ASCVD)和心力衰竭(HF)的綜合體),針對的是處於初級預防階段的一般人群(即基線時未患有心血管疾病的個體)。計算的風險估計新納入了HF作為一個終點,將年齡作為時間尺度,並考慮非CVD死亡的競爭風險。

基本PREVENT模型包括傳統的CVD風險因素和腎功能(eGFR)作為預測因子,並有針對特定高風險人群的附加模型,這些人群在CKM健康方面受損,當臨床指示或可用時,會納入尿液白蛋白與肌酐比率或糖化血紅蛋白(HbA1c)(即基線時未患有CVD但患有CKD或糖尿病的個體);此外,還會在可用時納入社會決定因素(SDOH)及社會剝奪指數。模型選項反映了針對特定個體的附加方法,當這些數據可用時,通過建模缺失指標,即使這些變數不可用,仍可進行使用。這在圖2的資訊圖中進行了總結。PREVENT(基本及附加)模型在外部驗證樣本中對CVD綜合體的性能表現出卓越的準確性和精確性(中位C統計數介於0.757至0.813之間,中位校準斜率介於0.94至1.05之間)。對於每種CVD亞型,均獲得了類似的結果(ASCVD的中位C統計數介於0.736至0.799之間,HF的中位C統計數介於0.809至0.841之間;ASCVD的中位校準斜率介於1.00至1.11之間,HF的中位校準斜率介於0.81至1.00之間)。

圖 2. PREVENT 基本及附加方程式。CVD 代表心血管疾病;PREVENT 是美國心臟協會預測心血管疾病事件的風險;SDI 為社會剝奪指數;SDOH 為健康的社會決定因素;UACR 為尿液白蛋白與肌酸酐比率。

以年齡作為時間尺度,可以構建任何年齡和時間範圍的風險估計。我們選擇將 10 年和 30 年風險作為主要模型輸出,因為臨床醫師對這兩個預測時間點較為熟悉。圖 3 展示了在指數年齡為 30 歲的個體中,整體心血管疾病 (CVD)、動脈粥樣硬化性心血管疾病 (ASCVD) 和心力衰竭 (HF) 在整個生命過程中的累計預測發生率。與存在 5 個次優風險因素的情況相比,擁有所有最佳風險因素的個體不僅心血管疾病風險較低,而且心血管疾病的發病時間顯著延後或疾病的壓縮 morbidity 明顯。

圖 3. 於 30 歲指數年齡的性別特異性心血管疾病(及其亞型)的預測累積風險。

最佳風險因素水平定義為非高密度脂蛋白膽固醇 3.5 毫摩爾/升或 135 毫克/分升;收縮壓 120 毫米汞柱;無糖尿病、非吸煙、無高血壓或他汀類藥物使用,以及估計的腎小管過濾率 90 毫升·分鐘–1·1.73 平方米–2。升高的風險因素水平定義為非高密度脂蛋白膽固醇 5.5 毫摩爾/升或 213 毫克/分升;收縮壓 150 毫米汞柱、糖尿病、當前吸煙,及估計的腎小管過濾率 45 毫升·分鐘–1·1.73 平方米–2,當有超過 1 個風險因素升高時,顯示所有組合的平均風險。模型已調整為非心血管死亡的競爭風險。HF 代表心力衰竭。

PREVENT 模型將年齡作為時間尺度,這意味著隨訪是以年齡而非日曆時間來衡量。這種方法與心血管疾病 (CVD) 結果的發展過程更為一致,因為這與個體的年齡有關而非日曆時間。這也提供了靈活性,可以通過從進入年齡和所需的隨訪結束年齡匯總估計來獲得任何隨訪期間的風險估計。我們的年齡尺度方法與較新的歐洲心血管風險預測算法 (SCORE [系統性冠心病風險評估]) 所用的方法相似。這比以往基於美國的風險預測模型(如 FHS)中的事件時間方法有所改進。先前發表的縱向或終身風險模型要求使用相同個體長期的事件發生率的經驗觀察,導致從較舊的非當代群體收集基線數據以獲得足夠的隨訪。

PREVENT 和 PCEs 中的人口統計學和臨床預測變數及相關結果的比較顯示在補充表 1 中。值得注意的是,PREVENT 和 PCEs 均不將個體級社會決定因素 (SDOH) 作為預測因子。

臨床意涵

補充圖 1 和圖 2 顯示了在廣泛的風險因素水平和選定組合下,估計的 10 年心血管疾病 (CVD)、動脈粥樣硬化性心血管疾病 (ASCVD) 和心力衰竭 (HF) 的預測風險範圍。選擇這些風險因素值旨在將臨床上有意義的範圍轉換為絕對風險估計。列首先按糖尿病狀態分層,然後按吸煙狀態和收縮壓水平(有或沒有抗高血壓治療)分類。行則按年齡層和具體的總膽固醇及高密度脂蛋白膽固醇 (HDL-C) 水平分組。所顯示的估計風險概率特定於一組假設的風險因素水平,以展示在潛在臨床特徵的廣泛光譜中風險如何變化。對於高於所包括的風險因素水平,心血管疾病的估計風險將會更高。根據不同風險情境對治療選擇的建議應繼續遵循根據特定共病情況(如糖尿病)可用的指南建議。PREVENT 計算的風險估計應考慮在未來的指導方針中,以納入絕對風險估計到基於風險的預防方法中,從而指導治療選擇。

PREVENT 對 ASCVD 的預測估計低於先前 PCEs 的 ASCVD 估計,這是因為 PREVENT 的當前衍生樣本中 ASCVD 風險較低,而 PCEs 則基於較舊的隊列。PREVENT 的新風險估計評估了總心血管疾病,這是 ASCVD 和 HF 的綜合體,考慮了非心血管死亡的競爭風險,基於更當代的數據,反映了世代趨勢,並將他汀治療納入預測因子,每個因素對風險估計都有重要影響。

在糖尿病患者中,強調總心血管疾病風險的分佈很重要,這加強了糖尿病並不自動與心血管疾病高風險相關的概念,且在糖尿病患者中預測風險的變異性很大,這可以為降低心血管疾病風險提供信息和定制新的治療選擇。未來,在討論高風險糖尿病患者的心臟保護性降血糖療法組合時,這一點可能會被考慮。無論預測風險如何,當前指南根據可用的臨床試驗數據建議,對所有年齡在 40 到 75 歲的糖尿病患者使用他汀類降脂治療。

風險估計與風險溝通的實施

在定義心血管健康管理 (CKM) 時,美國心臟協會 (AHA) 確認了兩個關鍵概念:(1)在 CKM 的早期階段,應將健康作為一種積極的構建,超越單純缺乏風險因素的概念,這基於 AHA 在 2010 年首次定義並於 2022 年修訂的心血管健康 (CVH) 框架,即「生命的八項基本要素」(Life’s Essential 8);(2)心血管疾病 (CVD) 的風險不僅限於動脈粥樣硬化性心血管疾病 (ASCVD),還應包括與 CVD 相關的相關慢性疾病的存在或缺失,這些疾病相互發生並具有共同的治療意義(例如,慢性腎病 CKD)。CKM 分期框架旨在與 PREVENT 的絕對風險評估結合,提供關於 CVD 風險的補充信息,如圖 4 所示。

圖 4. CKM 分期下的絕對心血管疾病 (CVD) 風險範圍。

描述各 CKM 階段中心血管疾病 (CVD) 風險的絕對分佈漸變,其中綠色代表低預測風險,黃色代表邊緣到中等預測風險,紅色則代表高預測風險。所示的 CKM 階段包括:階段 0(無 CKM 風險因素)、階段 1(過多或功能不正常的脂肪)、階段 2(代謝風險因素或慢性腎病 CKD)、階段 3(CKM 中的亞臨床 CVD 或亞臨床 CVD 的風險等價物 [高風險 CKD 或高預測風險])。CKM 代表心血管-腎臟-代謝;CVD 代表心血管疾病。

從 PREVENT 計算的風險估計可以在未來由臨床醫師和患者用於參與以患者為中心的風險討論,以便在確立可接受的風險閾值後進行共享決策,制定治療策略。因此,PREVENT 評估的風險可以實施在現有的 ACC/AHA 預防指導框架中,使臨床醫師和患者能夠進一步調整建議,特別是在邊緣到中等風險組別中,該組別的絕對預測風險範圍廣泛,從 5% 到 <20%。考量因素可以包括作為風險增強因素的定性因素(1)CKM 進展的風險因素,如 AHA 總統建議中詳細說明的(例如,慢性炎症性疾病、妊娠糖尿病、糖尿病家族史);(2)心血管疾病 (CVD) 的風險因素(例如,早發 ASCVD 的家族史),如 2019 年 ACC/AHA 初級預防指導中詳細說明的。這一框架將支持更個性化的心血管疾病預防方法,正如 2019 年 ACC/AHA 初級預防指導中所概述的。

所有患者都應接受健康和行為改變的建議,以促進與生命的八項基本要素(飲食、體力活動、睡眠、避免吸煙)一致的理想心血管健康指標,並根據現有風險因素接受指導下的醫療療法(例如,對於肥胖患者使用胰高血糖素樣肽-1 受體激動劑,或對於糖尿病患者使用他汀類藥物)。在基於風險的框架中,那些預測 10 年風險較高的患者應進行以患者為中心的討論,以加強風險因素的修正和考慮聯合療法,以最大限度地降低心血管疾病風險(例如,使用 ACE 抑制劑加鈉-葡萄糖共轉運蛋白-2 抑制劑加芬雷酮,或胰高血糖素樣肽-1 受體激動劑加鈉-葡萄糖共轉運蛋白-2 抑制劑)。然而,未來的研究應優先考慮生成指導方針修訂所需的證據,以確定將 PREVENT 方程的絕對風險評估與基於風險的預防方法結合,從而告知具體的治療選擇。

新興研究評估新型生物標誌物和廣泛的基因檢測值得進一步調查,但必須注意,無法識別目標治療途徑或可行反應的非特異性生物標誌物(超出目前可用的範疇)在臨床管理中的實用性有限。針對性或序列性診斷檢測可能最好僅保留給那些被認為具有附加預測價值的策略(例如,冠狀動脈鈣化指數 [CAC]),並可能優先應用於具有其他風險增強因素的患者,這些定性標誌物的累積負擔可能具有相關性。圍繞這些問題的共享決策,恰當地框定風險和潛在利益,將有助於提高患者的滿意度和依從性。基於這些方程式的在線風險估算工具、電子病歷插件和基於網絡的應用程序的開發對於廣泛的傳播和實施心血管疾病預防至關重要。特別是,多種 PREVENT 模型選項可以靈活地允許在可用或臨床指示時納入擴展的 CKM/社會決定因素 (SDOH) 變數,並有助於促進臨床醫師考慮 CKM/SDOH 變數,以便告知使用和討論及溝通。PREVENT 提供的更大精確性,加上其對當代人群的更大相關性,應該增強臨床醫師和患者對其使用的信心。因此,這種整合定量和定性風險評估及共享決策以指導風險因素治療算法的方法,也可以考慮納入個別的實踐指南(例如,膽固醇和血壓的管理),以在整個生命過程中調整因果風險因素。

為了成功,預防策略的制定還應考慮到個體層面的重要背景因素(例如,獲取和準備健康食品或參加體力活動的能力、獲取和負擔處方藥的能力以及健康素養)和社會層面的因素(例如,成本效益)。同樣,成功的心血管疾病預防還依賴於對依從性和反應的中間和生理標記的適當後續監測(例如,控制的血壓、穩定或減少的體重以及增加的瘦體重比例),這需要持續的醫療保健獲取。

方向與未回答的問題

越來越多的證據支持風險評估和基於風險的預防的重要性。然而,仍然存在重要的知識空白,具體情況如表 2 所示。

表 2. 心血管疾病 (CVD) 風險預測與基於風險的預防中的主要空白與未來方向
研究領域 主要差距和未解答的問題
SDOH 在 CVD 風險預測模型中具有預測效用的基於個人和地點的 SDOH 因素有哪些?
分析和整合多層次 SDOH 因子以進行 CVD 風險預測的最佳方法是什麼?
我們應該如何解決 SDOH 以降低與 CKM 風險相關的 CVD 風險?
確定在臨床環境中測量關鍵 SDOH 因素的方法?
新穎的預測因子和結果 將 CKD 進展預測納入基於風險的 CVD 預防的危險因子和可修改目標
評估預測 CVD 危險因子(例如高血壓、糖尿病)或亞臨床 CVD(例如冠狀動脈鈣化)的臨床效用
研究 CVD 的廣泛組學預測因子或總分的預測效用
確定高風險族群中診斷影像的成本效益,以識別亞臨床 CVD(例如,心房顫動患者中的超音波心動圖),以提高 CKM 分期的準確性
幹預與實施研究 確定對治療 CVD 危險因子、解決潛在風險和預防 CKD 進展的每種心臟保護療法有利的淨效益的風險閾值
制定實施 Life's Essential 8 的策略,將其作為衡量、修改和監控 CKM 健康狀況的框架
在年輕人中進行隨機臨床試驗,為早期幹預措施提供資訊並預防 CVD 危險因子或亞臨床疾病的發生
傳播與實施研究 將 PREVENT 整合到電子病歷中以支援風險評估的廣泛使用
對於 CVD 預測風險增加的族群,優化 CVD 風險因子控制的最佳策略是什麼
藥劑師提供的健康系統介入或社區為基礎的介入能否改善對 CVD 預測風險增加人口的風險因素控制

將預期治療益處納入心血管疾病預防

為了能夠付諸行動,風險估計需要轉化為有意義的臨床決策。一種方法是根據風險預測算法的輸出將個體分類為低風險、中等風險或高風險。更具臨床可行性的方法是將這些絕對風險與預期的治療策略所能帶來的相對風險降低結合起來,以量化預期的“治療益處”。然後,根據這一預期益處制定治療建議。這種預防益處模型已被證明在建議接受相同治療的人數時是最優的。這可以通過考慮一個簡單的例子來說明:一位具有高非高密度脂蛋白膽固醇(non-HDL-C)水平且心血管疾病中等預測風險的人,預期從降脂治療中獲得的益處(絕對風險的更高降低)將高於一位雖然風險更高但非高密度脂蛋白膽固醇水平最佳的人。這一概念在圖 5 中顯示,並且這種方法對於指導心血管保護性抗高血糖治療的使用,特別是對於健康狀況不佳的 CKM 患者,將尤其重要。

圖 5. 根據絕對風險和治療的相對風險降低估算預期治療益處(絕對風險降低)。

描述計算預防治療的淨效益或預期效益(定義為絕對風險降低 [ARR])的概念框架,假設預測的絕對風險(AR)範圍內的相對風險降低(RRR)是相似的。綠色個體代表低預測風險,黃色個體代表邊緣到中等預測風險,紅色個體代表高預測風險。因此,接受治療前,具有更高預測風險的個體的 ARR 大於具有較低預測風險的個體(即,ARR_red > ARR_yellow > ARR_green)。心血管疾病 (CVD)。

精煉心血管疾病風險預測的評估與社會決定因素 (SDOH) 的納入

在 PREVENT 方程式中存在的一些局限性應被視為未來改進的重點。樣本中包含的西班牙裔和亞洲人數量相對於全國人口的估計較少。大多數數據集中缺乏分解的種族和民族子組識別,限制了對這些子組的校準評估。這對南亞裔個體尤其相關,因為他們相比白人成年人面臨著較高的代謝疾病和動脈粥樣硬化心血管疾病 (ASCVD) 的風險。一項分析顯示,南亞裔成年人在 BMI 為 18.5 kg/m² 時的糖尿病風險與白人成年人在 BMI 為 24.9 kg/m² 時的風險相當。南亞裔民族身份作為社會構建,已在 CKM 總統建議和科學聲明中被突出為一種風險增強因素,並且已被確認與 CKM 狀況和心血管疾病風險的較高風險相關。因此,在這一子組中應用 PREVENT 可能導致心血管疾病風險的低估,並強調在開發風險預測方程式時,需要包含能代表目標人群多樣性的樣本。未來的研究應評估 PREVENT 在分解的種族和民族群體中的校準。

在某些種族和民族群體中,心血管疾病的發病率顯著較高的情況已被充分記錄。新興數據表明,社會因素是這種不成比例的心血管疾病風險的上游驅動因素。在 CARDIA 研究中的一項分析中,與白人相比,黑人個體的糖尿病過度風險幾乎完全歸因於鄰里、社會經濟、心理社會和行為因素的差異。在另一項來自 CARDIA 研究的分析中,類似的發現被用來解釋早期心血管疾病中的種族差距。社會決定因素作為心血管健康的決定因素在 Life’s Essential 8 框架的上下文化中得到了強調,該框架確定了促進健康和平等減少心血管疾病風險所需的重要個人、臨床和政策層面的方法。美國醫療保險和醫療補助服務中心最近發布了指導方針,旨在將社會決定因素的評估納入醫療保健系統。然而,仍然存在重大差距,未來的研究應優先考慮在可行實施之前評估和干預工具的開發,首先必須嚴格擴展社會決定因素數據的收集、報告和標準化。這與 CKM 醫療模型中提出的建議一致,並將有助於未來心血管疾病風險預測模型的改進。

早期介入心血管疾病風險評估與預防

越來越多的證據支持在生命早期(甚至在兒童期或可能在子宮內)開始進行風險預測的重要性。完整的生命歷程方法促進心血管健康、CKM 階段和心血管疾病風險評估的概念圖如圖 6 所示。當 CKM 健康下降且風險開始顯現時,實施有效策略的成效可能最大。在預防的角度,早期開始風險評估對於展開患者與臨床醫生之間的討論,監測和修改心血管疾病風險因素具有重大意義,這些風險因素通常在青少年向成人的過渡中出現。這一主題是美國心臟協會 2023 年科學建議的重點:“朝向兒科預防心臟病最佳實踐的路線圖”。

圖 6. 促進心血管健康 (CVH)、心臟-腎臟-代謝 (CKM) 健康分期和風險評估的生命歷程方法:驅動因素、決定因素和疾病。
  • 心臟-腎臟-代謝 (CKM) 的風險可能在出生之前就開始,這與子宮內的不良暴露有關(例如,妊娠糖尿病)。ASCVD 代表動脈粥樣硬化性心血管疾病;CKM,心臟-腎臟-代謝;CVD,心血管疾病;CVH,心血管健康;GDMT,指導性管理和療法;HF,心力衰竭;PREVENT,AHA 估算心血管事件風險。

另一個可能受益於心血管疾病 (CVD) 風險預測和預防的關鍵生命階段是圍產期(孕前、妊娠和產後)期間。這一階段尤其重要,因為孕前心血管健康 (CVH) 和不良妊娠結果與分娩成人的 CVD 風險相關聯。此外,對母體 CVH 的產前暴露與後代的 CVH 之間存在關聯,這表明在妊娠期間進行干預有潛力改善 CVD 風險的代際傳遞。因此,在未來的研究中,應考慮將不良妊娠結果(例如,妊娠糖尿病、妊娠高血壓疾病)納入作為新預測因子或相關結果。此外,考慮到 PREVENT 模型的年齡範圍從 30 歲開始擴展,當個體可能懷孕時,應評估模型在妊娠期間風險因素評估時的表現。由於在妊娠的第二和第三孕期中,代謝因素(例如,葡萄糖、脂質)可能會發生生理變化,因此,實施 PREVENT 可能需要限制在妊娠的第一孕期,以避免生理變化的影響。如果 PREVENT 在懷孕樣本中得到驗證,則妊娠代表著一個理想的“機會窗口”,在這個階段中,人們更容易獲得醫療服務並與臨床醫生進行更多接觸,這可以利用來更早開始有關終身 CVD 預防的討論。

預測不良腎臟結果以優化心血管疾病 (CVD) 的預防

累積暴露於已知的可修改或傳統心血管疾病 (CVD) 風險因子是 CVD 風險的主要原因,這一點已得到充分證實。傳統風險因子水平變化及其對 CVD 風險的影響已在《百萬心臟計畫》(Million Hearts Model)中建模。然而,隨著時間的推移,腎功能變化並未被納入考量。越來越多的證據表明,腎健康的下降與 CVD 結果不良相關,反之,腎臟保護療法也能改善 CVD 結果。

目前已經開發了幾個模型,以預測主要的腎臟結果(例如,急性腎損傷、腎功能下降和腎衰竭),這些模型適用於有和沒有糖尿病的人群。慢性腎病預後聯盟(CKD Prognosis Consortium)專門為預測腎功能下降≥40%或腎衰竭從 43 個數據集導出和驗證了新風險方程式,涉及超過 100 萬人,具有出色的辨識度和校準性。

最近,腎病進展的風險預測模型也被應用於分層和識別那些可能從針對腎臟健康的療法中獲得更大絕對益處的患者(即基於風險的預防)。在四項 TIMI(心肌梗死溶栓)臨床試驗的分析中,基線不良腎臟結果風險較高的患者在使用鈉-葡萄糖共轉運蛋白-2 抑制劑的療法中獲得了更大的絕對益處。未來的研究應調查腎功能下降的基於風險的預防是否能轉化為 CVD 風險的降低。此外,應探討新興的腎功能下降風險因子。例如,最近的 CHS 研究顯示,超聲心動圖的亞臨床心肌功能障礙與腎功能下降相關,這表明了心力衰竭前期與慢性腎病惡化風險之間的雙向通路。此外,模型應考慮使用胱抑素 C 計算 eGFR,因為這將變得越來越普遍並應用於臨床實踐中。

結論

對心血管疾病 (CVD) 的絕對風險評估仍然是臨床初級預防工作的基石。PREVENT 模型反映了心血管-腎臟-代謝 (CKM) 病況與 CVD 風險之間的相互關聯和上游影響。這些針對性別的風險方程式新近納入了 eGFR 作為預測因子,心衰作為結果,並且重要地排除了種族因素在風險預測估算中的影響。在選擇性模型中,加入腎臟、代謝和社會風險的附加指標突顯了進一步個性化風險評估和量身定制基於風險的建議的機會。

由於使用可輕易獲得的臨床因素,PREVENT 可應用於廣泛的臨床和社區環境中。所有照顧成年患者的臨床醫生均可實施 PREVENT,包括基層醫療、婦產科、心臟病學、腎臟病學和內分泌學等領域。儘管 CVD 的定量風險評估將持續演變,反映出風險因子流行率和治療模式的世俗趨勢、社會和生物預測因子的精煉以及新療法的出現,但 PREVENT 的發展為促進初級預防的優先性提供了重要的下一步,並在整個 CKM 光譜中公平改善人口健康。

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