Predictive value of vascular health indicators on newly cardiovascular events: Preliminary validation of Beijing vascular health stratification system

LIU Huan1,2,*, HE Ying-dong3,*, LIU Jin-bo1,2, HUANG Wei1, ZHAO Na1, ZHAO Hong-wei1, ZHOU Xiao-hua ,2,3,△, WANG Hong-yu ,1,2,△

1. Vascular Medicine Center, Peking University Shougang Hospital, Beijing 100144, China

2. Vascular Health Research Center of Peking University Health Science Center, Beijing 100191, China

3. Department of Biostatistics, Peking University, Beijing International Center for Mathematical Research, Beijing 100871, China

摘要

目的 探索血管健康指標(包括頸-股動脈脈搏波傳導速度、頸-橈動脈脈搏波傳導速度、心踝血管指數(shù)和踝臂指數(shù))與冠狀動脈粥樣硬化性心臟病(簡稱冠心病)和腦梗塞的關系,初步評估北京血管健康分級的預測價值。方法 研究納入2010—2017年首鋼醫(yī)院血管醫(yī)學科至少有2次住院記錄的受試者,排除基線時血管指標數(shù)據(jù)缺失且患有冠心病或腦梗塞的患者。建立兩個隊列,隊列1(冠心病)入組467例受試者[平均年齡(63.4±12.3)歲,女性42.2%],隊列2(腦梗塞)入組658例受試者[平均年齡(64.3±12.2)歲,女性48.7%],分別應用Cox比例風險回歸建立冠心病或腦梗塞的預測模型。結果 隊列1和隊列2的中位隨訪時間分別為1.9年和2.1年,隨訪期間,隊列1中有164例首發(fā)冠心病事件發(fā)生,隊列2中有117例首發(fā)腦梗塞事件發(fā)生。將4種血管健康指標同時作為連續(xù)變量進行多變量調(diào)整分析,隊列1中,4種指標均有統(tǒng)計學意義(P均<0.05);隊列2中,僅心踝血管指數(shù)有統(tǒng)計學意義(P<0.05)。未調(diào)整模型中,北京血管健康分級對于冠心病和腦梗塞的預測價值均有統(tǒng)計學意義(P均<0.05),而在多變量調(diào)整模型中,北京血管健康分級僅對冠心病具有預測價值(P<0.05)。結論 不同的血管健康指標對于冠心病和腦梗塞的預測價值不同,其中心踝血管指數(shù)可能是一種較為穩(wěn)定的指標。北京血管健康分級對于冠心病具有預測價值,而對于腦梗塞的預測價值還需進一步研究。

關鍵詞：心血管疾病;危險因素;隊列研究;北京血管健康分級

Abstract

Objective: To explore the predictive value of carotid femoral artery pulse wave velocity (CF-PWV), carotid radial artery pulse wave velocity (CR-PWV), cardio-ankle vascular index (CAVI), and ankle brachial index (ABI) on coronary heart disease (CHD) and cerebral infarction (CI), and the preliminary validation of Beijing vascular health stratification (BVHS).Methods: Subjects with at least 2 in-patient records were included into the study between 2010 and 2017 from Vascular Medicine Center of Peking University Shougang Hospital. Subjects with CHD or CI, and without data of vascular function at baseline were excluded. Eventually, 467 subjects free of CHD [cohort 1, mean age: (63.4±12.3) years, female 42.2%] and 658 subjects free of CI [cohort 2, mean age: (64.3±12.2) years, female 48.7%] at baseline were included. The first in-patient records were as the baseline data, the second in-patient records were as a following-up data. Cox proportional hazard regression was used to establish the predictive models of CHD or CI derived from BVHS by multivariable-adjusted analysis.Results: The median follow-up time of cohort 1 and cohort 2 was 1.9 years and 2.1 years, respectively. During the follow-up, 164 first CHD events occurred in cohort 1 and 117 first CI events occurred in cohort 2. Four indicators were assessed as continuous variables simultaneously by multivariable-adjusted analysis. In cohort 1, CF-PWV, CR-PWV, ABI, and CAVI reached statistical significance in the multivariable-adjusted models (P<0.05). In cohort 2, only CAVI (P<0.05) was of statistical significance. In addition, the higher CF-PWV became a protector of CHD or CI (P<0.05). The prediction value of BVHS reached the statistical significance for CHD and CI in the unadjusted models (all P<0.05), however, BVHS could only predict the incidence of CHD (P<0.05), but not the incidence of CI (P>0.05) in the multivariable-adjusted models. CF-PWV, CR-PWV, ABI, and CAVI were associated factors of CHD independent of each other (P<0.05), only CAVI (P<0.05) was the risk factor of CI independent of the other three.Conclusion: The different vascular indicators might have different effect on CHD or CI. CAVI might be a stable predictor of both CHD and CI. Higher baseline CF-PWV was not necessarily a risk factor of CHD or CI because of proper vascular health management. BVHS was a potential factor for the prediction of CHD, and further research is needed to explore the prediction value for CI.

Keywords：Cardiovascular disease;Risk factors;Cohort studies;Beijing vascular health stratification

本文引用格式

劉歡, 何映東, 劉金波, 黃薇, 趙娜, 趙紅薇, 周曉華, 王宏宇. 血管健康指標對新發(fā)心腦血管事件的預測價值:北京血管健康分級標準的初步驗證. 北京大學學報(醫(yī)學版)[J], 2020, 52(3): 514-520 doi:10.19723/j.issn.1671-167X.2020.03.018

LIU Huan, HE Ying-dong, LIU Jin-bo, HUANG Wei, ZHAO Na, ZHAO Hong-wei, ZHOU Xiao-hua, WANG Hong-yu. Predictive value of vascular health indicators on newly cardiovascular events: Preliminary validation of Beijing vascular health stratification system. Journal of Peking University(Health Sciences)[J], 2020, 52(3): 514-520 doi:10.19723/j.issn.1671-167X.2020.03.018

目前血管結構病變(如管腔狹窄或閉塞)被常規(guī)用于心血管疾病的風險評估,盡管以往研究已發(fā)現(xiàn)動脈功能障礙與心血管疾病的關系,但尚未引起臨床重視。一些無創(chuàng)指標已被用來量化評估血管健康,包括踝臂指數(shù)(ankle brachial index,ABI)、頸-股動脈脈搏波傳導速度(carotid-femoral artery pulse wave velocity,CF-PWV)、頸-橈動脈脈搏波傳導速度(carotid-radial artery pulse wave velocity,CR-PWV)、心踝血管指數(shù)(cardio-ankle vascular index,CAVI)。ABI是踝部動脈與肱動脈收縮壓之比,常作為下肢動脈粥樣硬化閉塞的診斷標準之一[1],還是其他血管床發(fā)生動脈粥樣硬化的提示指標,低的ABI還被認為是西方和亞洲人群心血管疾病的獨立預測因子[2,3]。CF-PWV作為動脈硬化評估指標的研究較多,其增高是患病人群和一般人群的心血管疾病危險因子[4,5],目前尚未發(fā)現(xiàn)CR-PWV與心血管疾病有關[6,7,8]。CAVI也是動脈硬化的指標之一,但其在檢測時不受即刻血壓的影響[9],有研究發(fā)現(xiàn)CAVI與心血管疾病的危險因素有關[10,11,12,13]。

關于上述指標的研究尚存在以下不足:(1)ABI和CF-PWV的相關研究眾多,但是關于CR-PWV和CAVI的研究以及多種指標聯(lián)合評估的研究較少;(2)大多數(shù)研究的是西方人群,關于亞洲人群的研究多是日本人群,關于中國人群的隊列研究尚缺乏。一些血管健康指標已被證實為心血管疾病的獨立危險因素,用于心血管事件的預測,且血管健康指標聯(lián)合傳統(tǒng)的危險因素能夠提高心血管事件的預測能力[14,15,16]。本研究團隊在總結了多年的臨床及科研經(jīng)驗后,提出了血管健康綜合評估系統(tǒng)的概念,并提出了以血管為評估靶點的北京血管健康分級標準(Beijing vascular health stratification, BVHS)[17,18],然而此分級系統(tǒng)尚未被驗證其應用價值。

因此,本研究基于醫(yī)院內(nèi)數(shù)據(jù)設計回顧性隊列研究,目的在于在中國人群中,探索不同血管健康指標對兩種主要心血管疾病——冠狀動脈粥樣硬化性心臟病(簡稱冠心病)和腦梗塞(cerebral infarction,CI)預測的聯(lián)合效應以及相對權重,初步評估BVHS的預測價值。

1 資料與方法

1.1 研究人群

本研究設計為基于醫(yī)院內(nèi)數(shù)據(jù)的回顧性隊列研究,使用北京血管疾病人群評估研究(Beijing Vascular Disease Patients Evaluation Study,BEST Study)的部分數(shù)據(jù)。BEST研究(Clinical Trials.gov Identifier: NCT02569268)是一項自2010年在北京大學首鋼醫(yī)院血管醫(yī)學中心開展的前瞻性隊列研究[19]。

收集2010—2017年在首鋼醫(yī)院血管醫(yī)學科住院就診人群(涵蓋各種血管相關疾病,主要包括高血壓、糖尿病、冠心病、腦梗塞和外周動脈疾病等)的醫(yī)療數(shù)據(jù)。

建立兩個隊列,隊列1(冠心病隊列),隊列2(腦梗塞隊列),兩個隊列的入選標準為:(1)年齡、性別不限;(2)至少有一次住院記錄(作為基線數(shù)據(jù)資料),且在其當次住院后至少有一次住院記錄(作為隨訪記錄數(shù)據(jù))。

隊列1和隊列2的排除標準:(1)基線時血管健康指標數(shù)據(jù)缺失;(2)基線時患有冠心病者(隊列1)、患有腦梗塞者(隊列2)。

隊列1入選467例無冠心病受試者,隊列2入選658例無腦梗塞受試者,入選流程圖見圖1。

圖1

圖1  受試者入選流程圖

Figure 1  Flow diagram of subject inclusion process

CHD, coronary heart disease; CI, cerebral infarction.

BEST研究方案符合1975年《赫爾辛基宣言》,且通過北京大學首鋼醫(yī)院倫理委員會批準(批件號IRBK-2017-017-01),入選受試者均簽署書面知情同意書。

1.2 血管健康指標檢查

血管健康指標測量前囑受檢者休息、保持安靜并平臥位5~10 min,如運動后需靜息20 min,受檢者去枕仰臥體位,雙手手心向上置于身體兩側。

CF-PWV和CR-PWV使用自動血管功能檢查設備(Artech Medical, Pantin, 法國)檢測,其原理為脈搏波在動脈系統(tǒng)的兩個既定點之間的傳播速度通過測量兩點之間的傳導時間(t)和距離(L)求得,計算公式為PWV(m/s)=L/t。

CAVI和ABI使用血管篩查系統(tǒng)(VS-1000,Fukuda Denshi,日本)檢測,將四肢血壓袖帶縛于被檢測者上臂及下肢踝部,將2個心電電極分別置于雙腕部以采集心電信號,將心音傳感器放置在胸骨上第二肋間的位置,儀器自動檢測雙側CAVI和ABI。本研究中,ABI取平均值(因ABI數(shù)值反映動脈狹窄閉塞的病變程度,本研究中取雙側平均值用于評估下肢動脈的病變負荷),CAVI取兩側中較大值。

1.3 心血管危險因素的臨床評估和定義

收集記錄基線時吸煙、飲酒數(shù)據(jù),高血壓、糖尿病和高脂血癥的診斷數(shù)據(jù)來自于首次住院時醫(yī)療文件記錄,身高、體質(zhì)量、心率、收縮壓和舒張壓由CAVI設備同時獲得,體重指數(shù)(body mass index,BMI)=體質(zhì)量/身高2,平均動脈壓(mean arterial pressure,MAP)=2/3舒張壓+1/3收縮壓。

1.4 簡化的BVHS

BVHS是一種基于血管結構和功能(如動脈內(nèi)皮功能、動脈僵硬度和動脈狹窄)進行綜合評估的新的血管健康評估系統(tǒng)。本研究中,僅用動脈僵硬度和動脈狹窄指標,將BVHS簡化為七級評分系統(tǒng),定義及賦值為: 1: 動脈硬化,右側CF-PWV>9 m/s或任意一側CAVI>9; 0: 無動脈硬化,右側CF-PWV<9 m/s且雙側CAVI<9。

動脈狹窄程度的評估基于影像學檢查,包括顱腦磁共振成像血管造影、外周動脈和冠狀動脈的X線血管造影、計算機斷層掃描血管造影(computed tomography angiography,CTA)或血管超聲(頸動脈、鎖骨下動脈、下肢動脈、腹主動脈)。如無影像學診斷報告,則被認定為動脈狹窄程度為1,即無血管管腔狹窄,賦值如下:1:無血管管腔狹窄;2:血管管腔狹窄<50%;3:血管管腔狹窄50%~75%;4:血管管腔狹窄>75%。最終簡化的BVHS詳見表1。

表1  簡化的北京血管健康分級賦值

Table 1  Simplified BVHS system

Artery stenosisArterial stiffnessSimplified BVHS10011202133041540617

Artery stenosis including peripheral artery and coronary artery detected by vascular ultrasound or computed tomography angiography or angiography. 1, 2, 3, 4, correspond to no vascular lumen stenosis, vascular lumen stenosis<50%, vascular lumen stenosis 50%-75%, vascular lumen stenosis>75%. Arterial stiffness=1, corresponds to CF-PWV>9 m/s or CAVI>9 in either side, and otherwise=0. BVHS, Beijing vascular health stratification.

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1.5 結局

隊列1中主要的結局變量是冠心病,隊列2中主要的結局變量是腦梗塞。對于隨訪的醫(yī)療記錄,再次核實冠心病及腦梗塞的診斷。冠心病定義為有心肌梗死、明確的心絞痛、復蘇的心臟驟停、冠狀動脈旁路移植術或血管成形術的病史。腦梗塞的診斷來自于顱腦磁共振檢查結果。

1.6 統(tǒng)計學分析

隊列1和隊列2中應用同樣的統(tǒng)計分析方法,所有受試者按照年齡被分為6組:年齡<40歲、40~49歲、50~59歲、60~69歲、70~79歲和≥80歲。以性別和年齡組特定的中位數(shù)作為界定值來定義高或低的血管健康指標,包括CF-PWV、CR-PWV、ABI和CAVI。采用兩獨立樣本t檢驗和卡方檢驗比較兩組之間的差異,以Cox比例風險模型檢驗4種血管健康指標以及BVHS綜合評估系統(tǒng)與冠心病或腦梗塞之間的關系。本研究以單一血管健康指標或4個血管健康指標同時作為自變量,冠心病或腦梗塞為因變量,調(diào)整其他混雜因素,建立如下模型:(1)單一血管健康指標作為二分類變量(高或低)建立多變量調(diào)整模型;(2)單一血管健康指標作為連續(xù)變量建立多變量調(diào)整模型;(3)4個血管健康指標同時作為連續(xù)變量建立多變量調(diào)整模型;(4)以BVHS建立模型。本研究為將年齡、性別、吸煙、飲酒、BMI、心率、平均動脈壓、高血壓、糖尿病、高脂血癥、基線時腦梗塞(隊列1)或基線時冠心病(隊列2)進行調(diào)整的多變量分析,雙側P<0.05為差異有統(tǒng)計學意義,所有分析均使用R軟件(版本3.5.1,奧地利,維也納,R統(tǒng)計計算基金會)進行。

2 結果

2.1 隊列1和隊列2的一般臨床特點

隊列1和隊列2的中位隨訪時間分別為1.9年和2.1年,隨訪期間,隊列1中有164例首發(fā)冠心病事件發(fā)生,隊列2中有117例首發(fā)腦梗塞事件發(fā)生(表2)。

表2  隊列1人群和隊列2人群的基線特點

Table 2  Baseline characteristics of cohort 1 and cohort 2

VariableCohort 1
(n=467)Cohort 2
(n=658)Age/years63.4±12.364.3±12.2Female/%42.248.7Body mass index/(kg/m2)25.2±3.825.6±6.1Heart rate/(beats/min)70.3±11.671.7±42.6Mean artery pressure/mmHg101.8±11.9101.6±14.5Smoking/%30.026.6Drinking/%27.023.1Diabetes/%23.329.7Hypertension/%62.764.6Hyperlipidemia/%57.864.2Coronary heart disease
(baseline/endpoint)/%52.1/66.1Cerebral infarction
(baseline/endpoint)/%32.8/41.8CF-PWV/(m/s)11.6±2.911.6±2.7CR-PWV/(m/s)9.2±1.79.1±1.8CAVI8.7±1.98.6±1.9ABI1.02±0.201.01±0.21Median follow-up time/years1.92.1Number of events164117

Values are ?x±s for continuous variables or % for categorical variables. CF-PWV, carotid-femoral artery pulse wave velocity; CR-PWV, carotid-radial artery pulse wave velocity; ABI, ankle brachial index; CAVI, cardio-ankle vascular index.

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2.2 4種血管健康指標對于冠心病和腦梗塞事件的預測

由表3~6可見,隊列1中,將4種血管健康指標分別作為二分類變量進行多變量調(diào)整的Cox分析發(fā)現(xiàn),CF-PWV、CR-PWV和CAVI有統(tǒng)計學意義,而ABI并無統(tǒng)計學意義。將4種血管健康指標分別作為連續(xù)變量進行多變量調(diào)整的Cox分析發(fā)現(xiàn),CF-PWV、CR-PWV和ABI均具有統(tǒng)計學意義,而CAVI無統(tǒng)計學意義。將4種血管健康指標同時作為連續(xù)變量進行多變量調(diào)整分析,4種指標均具有統(tǒng)計學意義。

表3  隊列1中4種血管健康指標分別對于冠心病風險的預測

Table 3  Risk of coronary heart disease event in cohort 1 in groups classified by four arterial health indicators (high vs. low) and per 1-SD increase in them

ItemsBinary (high vs. low)Continuous (per 1-SD increase)UnadjustedMultivariable-adjustedUnadjustedMultivariable-adjustedCF-PWVHR (95%CI)0.82 (0.60-1.11)0.68 (0.48-0.96)0.92 (0.78-1.08)0.65 (0.54-0.77)P value0.1980.0280.298<0.001CR-PWVHR (95%CI)0.64 (0.47-0.87)0.70 (0.59-0.83)0.70 (0.59-0.83)0.64 (0.53-0.76)P value0.004<0.001<0.001<0.001ABIHR (95%CI)0.90 (0.66-1.23)1.01 (0.73-1.41)0.80 (0.70-0.91)0.85 (0.73-1.00)P value0.5260.946<0.0010.044CAVIHR (95%CI)1.33 (0.97-1.81)1.54 (1.09-2.18)1.29 (1.12-1.49)1.19 (0.99-1.43)P value0.0750.014<0.0010.062

Multivariable-adjusted model is adjusted for age, gender, smoking, alcohol use, body mass index, heart rate, mean arterial pressure, hypertension, diabetes mellitus, cerebral infarction at baseline and hyperlipoidemia. CF-PWV, carotid-femoral artery pulse wave velocity; CR-PWV, carotid-radial artery pulse wave velocity; ABI, ankle brachial index; CAVI, cardio-ankle vascular index; SD, standard deviation; CI, confidence interval; HR, hazard ratio.

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表4  隊列2中4種血管健康指標分別對于腦梗塞風險的預測

Table 4  Risk of cerebral infarction event in cohort 2 in groups classified by four arterial health indicators (high vs. low) and per 1-SD increase in them

ItemsBinary (high vs. low)Continuous (per 1-SD increase)UnadjustedMultivariable-adjustedUnadjustedMultivariable-adjustedCF-PWVHR (95%CI)0.79 (0.55-1.14)0.62 (0.42-0.91)1.14 (0.95-1.36)0.80 (0.66-0.97)P value0.2090.0160.1590.025CR-PWVHR (95%CI)0.95 (0.66-1.37)0.75 (0.51-1.12)0.87 (0.72-1.07)0.90 (0.73-1.12)P value0.7840.1700.1820.344ABIHR (95%CI)0.97 (0.67-1.39)1.01 (0.69-1.49)0.86 (0.72-1.01)1.04 (0.85-1.27)P value0.8520.9490.0760.697CAVIHR (95%CI)1.93 (1.32-2.83)1.86 (1.27-2.80)1.57 (1.36-1.81)1.35 (1.12-1.64)P value<0.0010.003<0.0010.002

Multivariable-adjusted model is adjusted for age, gender, smoking, alcohol use, body mass index, heart rate, mean arterial pressure, hypertension, diabetes mellitus, coronary heart disease at baseline and hyperlipoidemia. Abbreviations as in Table 3.

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表5  隊列1中4種血管健康指標同時對于冠心病風險的預測

Table 5  Risk of coronary heart disease event in cohort 1 per 1-SD increase in four arterial health indicators

ModelIndicatorHR (95%CI)P valueUnadjustedCF-PWV0.82 (0.69-0.97)0.023CR-PWV0.75 (0.63-0.88)<0.001ABI0.78 (0.67-0.90)<0.001CAVI1.42 (1.22-1.64)<0.001Multivariable-adjustedCF-PWV0.71 (0.59-0.86)<0.001CR-PWV0.70 (0.57-0.84)<0.001ABI0.84 (0.71-0.99)0.042CAVI1.32 (1.11-1.58)0.002

Abbreviations and footnotes as in Table 3.

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表6  隊列2中4種血管健康指標同時對于腦梗塞風險的預測

Table 6  Risk of cerebral infarction event in cohort 2 per 1-SD increase in four arterial health indicators

ModelIndicatorHR (95%CI)P valueUnadjustedCF-PWV1.04 (0.87-1.25)0.639CR-PWV0.87 (0.72-1.06)0.177ABI0.86 (0.72-1.03)0.105CAVI1.55 (1.35-1.78)<0.001Multivariable-adjustedCF-PWV0.83 (0.69-1.00)0.055CR-PWV0.92 (0.74-1.13)0.417ABI0.99 (0.80-1.23)0.947CAVI1.33 (1.11-1.60)0.002

Abbreviations as in Table 3. Footnotes as in Table 4.

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隊列2中,將4種血管健康指標分別作為二分類變量和連續(xù)變量進行多變量調(diào)整的Cox分析發(fā)現(xiàn),只有CF-PWV和CAVI有統(tǒng)計學意義。將4種血管指標同時作為連續(xù)變量進行多變量調(diào)整分析,只有CAVI具有統(tǒng)計學意義。

2.3 簡化的BVHS對于冠心病和腦梗塞的預測價值

未調(diào)整的Cox分析發(fā)現(xiàn),簡化的BVHS對于冠心病和腦梗塞的預測均有統(tǒng)計學意義,而在多變量調(diào)整的Cox分析中,簡化的BVHS僅對冠心病的預測有統(tǒng)計學意義,而對腦梗塞的預測沒有統(tǒng)計學意義(表7)。

表7  簡化的BVHS對于冠心病和腦梗塞的預測價值

Table 7  Predictive value of simplified BVHS in prediction of coronary heart disease and cerebral infarction events

EventsModelHR (95%CI)P valueCoronary
heart diseaseUnadjusted1.20 (1.13-1.27)<0.001Multivariable-adjusted1.17 (1.10-1.25)<0.001Cerebral
infarctionUnadjusted1.20 (1.00-1.45)0.048Multivariable-adjusted1.07 (0.87-1.32)0.518

Coronary heart disease cohort: multivariable-adjusted model is adjusted for age, gender, smoking, alcohol use, body mass index, heart rate, mean arterial pressure, hypertension, diabetes mellitus, cerebral infarction at baseline and hyperlipoidemia. Cerebral infarction cohort: multivariable-adjusted model is adjusted for age, gender, smoking, alcohol use, body mass index, heart rate, mean arterial pressure, hypertension, diabetes mellitus, coronary heart disease at baseline and hyperlipoidemia. BVHS, Beijing vascular health stratification; CI, confidence interval; HR, hazard ratio.

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3 討論

本研究發(fā)現(xiàn)4種血管健康指標CF-PWV、CR-PWV、ABI和CAVI同時是冠心病的獨立相關因素,且相互之間獨立,而只有CAVI升高是腦梗塞的獨立危險因素,且不受其他3種指標的影響。這些結果提示,不同的血管健康指標對于冠心病和腦梗塞的預測價值不同,而且CAVI可能是冠心病和腦梗塞比較穩(wěn)定的預測指標。此外,本研究分析了BVHS的價值,發(fā)現(xiàn)其對于冠心病具有預測價值,而對于腦梗塞的預測價值還需要進一步的研究。

關于血管健康指標的研究較多,但大多數(shù)研究僅圍繞某一指標進行單獨研究,很少研究多種血管健康指標在同一隊列中的價值。目前為止,較高的CF-PWV一直被認為是心血管事件的危險因素。一項包括19項研究的薈萃分析估計CF-PWV的風險比(hazard risk, HR)為1.25(每增加1個標準差,95%CI為1.19~1.31),且這些研究均提示較高的CF-PWV是顯著的危險因子[5]。然而,本研究中較高的CF-PWV在一些研究分析中并不是危險因素,而表現(xiàn)為冠心病或腦梗塞的保護因子。究其原因,可能是本研究在基線時具有較高CF-PWV的人群被給予了更多的系統(tǒng)性治療和管理,延緩了CF-PWV的進展,甚至使CF-PWV水平降低,從而導致基線時較高的CF-PWV成為了冠心病或腦梗塞事件的保護因素。由此可見,基線時即使具有較高的CF-PWV水平,但是通過系統(tǒng)管理和治療,較高的CF-PWV可延緩年齡相關的動脈硬化進展,甚或是逆轉,從而導致這部分人群的心腦血管事件發(fā)生率較低,也初步說明,僅一次血管健康狀況評估并不能反映未來心血管事件的風險,而是要終身評估和維護血管健康,從而降低心腦血管事件的發(fā)生。此外,CF-PWV指標在檢測時容易受到檢測時即刻血壓變化的影響,本研究結果也初步證實CAVI是一種更加穩(wěn)定的指標,本研究中對ABI和CAVI的研究結果與既往其他研究結果一致,通常情況下,截點值0.9被用來評估ABI的高低。Ohkuma等[2]通過分析個體數(shù)據(jù)的薈萃分析研究發(fā)現(xiàn),與ABI為1.10~1.19相比,ABI≤0.9對于心血管事件的HR為1.60,Hong等[20]的薈萃分析中發(fā)現(xiàn)了更大的HR為2.22。本研究中,血管健康指標用年齡和性別校正的中位數(shù)來作為截點值,而不是用特定的截點數(shù)值,這樣不同的指標分析結果都以類似的方式展示。不論是作為二分類變量還是連續(xù)變量,較低的ABI都是冠心病的顯著危險因子,而其對于腦梗塞并無統(tǒng)計學意義。本研究中CAVI對于冠心病和腦梗塞的HR估測值與Satoh-Asahara等[13](HR=1.44,每增加一個標準差,95%CI:1.02~2.02)和Sato等[12](HR=1.126,每增加一個標準差,95%CI:1.006~1.259)的研究結果類似。

本研究團隊在2015年提出了新的血管健康分級——BVHS標準[18],本研究中簡化了BVHS,初步分析結果發(fā)現(xiàn),其對于冠心病的預測是一個有效的風險評估系統(tǒng),而對于腦梗塞的預測價值還需要進一步研究確定。

本研究發(fā)現(xiàn),4種血管健康指標同時是冠心病和腦梗塞的預測因子,且相互之間獨立,承擔不同的權重,其中CAVI是一種更為穩(wěn)定的指標,此外,通過有效的血管健康管理和干預,即使基線時較高的CF-PWV水平也并不一定是心腦血管事件的危險因素。BVHS在中國人群中對于冠心病具有預測價值,而對于腦梗塞的預測價值尚需研究。今后將進行進一步的前瞻性隊列研究,以驗證本研究結果,并不斷完善BVHS分級系統(tǒng)。

本研究有以下局限性:首先,數(shù)據(jù)收集并未按照標準的隊列研究設計標準收集,而是利用醫(yī)院現(xiàn)有數(shù)據(jù)進行分析,本研究的事件發(fā)生率較高,原因主要是由回顧性構建隊列所造成,與隊列構建方法和入組標準有關。本研究入組標準主要是患者需要有至少2次住院記錄,第一次作為基線,第二次作為隨訪,這樣就導致了隊列人群事件發(fā)生率過高的問題,因為那些不發(fā)病的患者未回來住院,也就不在隊列里,這是本研究的一個重要不足。其次,隨訪并未經(jīng)過嚴格的研究設計,基線后,將每位受試者的每次住院就診記錄作為隨訪數(shù)據(jù),因此有可能此人的心血管事件在患者此次來醫(yī)院前就已經(jīng)發(fā)生,或者選擇了其他醫(yī)院就診。第三,本研究僅入選心血管疾病高危人群(主動就診患者),因此研究結果可能并不適用于一般人群。

盡管本研究并未經(jīng)嚴格的方案設計和實施,但對于無創(chuàng)血管健康評估指標建立的綜合評估系統(tǒng)和分級標準的臨床應用價值進行了初步探索,并得到了較好的結果,因此,本結果對于后續(xù)進行嚴謹方案設計的研究開展,提供了研究價值。

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BACKGROUND AND PURPOSE: The ankle-brachial index (ABI) is a fast, cheap, noninvasive indicator of atherosclerotic burden that may also be a predictor of stroke recurrence. In this systematic review and meta-analysis, we sought to explore ABI's merit as a marker for stroke recurrence and vascular risk by synthesizing the data currently available in stroke literature. METHODS: We searched Embase, MEDLINE, and Pubmed databases for prospective cohort studies that included consecutive patients with stroke and transient ischemic attack, measured ABI at baseline, and performed a follow-up assessment at least 12 months after initial stroke or transient ischemic attack. The following end points were chosen for our analysis: recurrent stroke and combined vascular end point (recurrent vascular event or vascular death). Crude risk ratios and adjusted Cox proportional hazard ratios were combined separately using the random-effects model. Study-level characteristics (eg, percent of cohort with a history of hypertension, average cohort age, level of adjustment, and mean follow-up duration) were included as covariates in a metaregression analysis. RESULTS: We identified 11 studies (5374 patients) that were not significantly heterogeneous. Pooling adjusted hazard ratios showed that low ABI was associated with both an increased hazard of recurrent stroke (hazard ratio, 1.70; 95% confidence interval, 1.10-2.64) and an increased risk of vascular events or vascular death (hazard ratio, 2.22; 95% confidence interval, 1.67-2.97). CONCLUSION: Our results confirm the positive association between ABI and stroke recurrence. Further studies are needed to see whether inclusion of ABI will help improve the accuracy of prediction models and management of stroke patients.

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