Risk Stratification in Patients with Ischemic Stroke and Residual Cardiovascular Risk with Current Secondary Prevention

Figures & data

Figure 1 Flowchart of inclusion and exclusion of patients.

Table 1 Characteristics at the Index Stay (N = 465)

	n (% of N) or Mean (SD)
Age	69.0 (8.1)
Sex, male	287 (62%)
Atrial fibrillation	101 (22%)
Diabetes mellitus	92 (20%)
History of hypertension	252 (54%)
History of hypercholesterolemia	253 (54%)
Previous cerebrovascular disease	108 (23%)
Coronary artery disease	79 (17%)
Peripheral artery disease	35 (8%)
Number of vascular areas affected^a 1, 2 or 3	369 (79%), 78 (17%), 18 (4%)
Heart failure	11 (2%)
Current smoker	109 (24%)
Previous smoker	174 (38%)
Estimated GFR^b (mL/min/1.73 m^2)	79 (16)
Body Mass Index (kg/m^2)	26.6 (4.2)
High-sensitive CRP concentration (mg/L)	9.6 (18.0)
Stroke subtype^c (n = 450)
Large artery disease	49 (11%)
Cardioembolic	103 (23%)
Small vessel disease	105 (23%)
Other causes	12 (3%)
Unknown or multiple causes	181 (40%)
NIHSS^d at discharge (n = 437)	1.7 (2.4)
Charlson Comorbidity Index	3.7 (1.9)
Frail^e	34 (7%)
Cognitive impairment^f	13 (3%)

Notes: ^aNumber of vascular areas were one if only stroke, two if combined with either coronary artery disease or peripheral artery disease, and three if all three areas were affected. ^bGFR calculated by CKD-EPI equation. ^cAccording to TOAST: Trial of ORG 10172 in Acute Stroke Treatment. ^dStroke severity according to National Institutes of Health Stroke Scale (NIHSS). ^eMeasured by the 5-item Fried criteria. ^fDefined as score ≥ 3 on Global Deterioration Scale. Detailed definitions in Supplementary Methods.

Abbreviations: CRP, C-reactive protein; eGFR, Estimated glomerular filtration rate.

Table 2 Risk Factor Levels at the Index Stay and the 3-Month Visit (n = 465)

	Index Stay^a	3-Month Visit
Systolic blood pressure (mmHg)	140 (20)	140 (19)
Diastolic blood pressure (mmHg)	80 (13)	83 (12)
LDL-C (mmol/L)	3.1 (1.1)	2.1 (0.8)
HDL-C (mmol/L)	1.4 (0.5)	1.5 (0.5)
Total cholesterol (mmol/L)	4.9 (1.3)	4.0 (0.9)
Current smoking	109 (23%)	55 (12%)
Use of secondary preventive medications
Lipid-lowering drugs^b	415 (89%)	412 (89%)
Antihypertensive drugs^c	320 (69%)	338 (73%)
Antithrombotic drugs^d	456 (98%)	455 (98%)

Notes: Values are mean (standard deviation) or n (%). Missing values are imputed by single imputation using predictive mean matching. ^aConcentrations of cholesterol were measured the first day after admission and blood pressure levels at day 7 or at the day of discharge, use of medications was assessed at discharge. ^bUse of lipid-lowering drugs was defined as use of drugs belonging to ATC group C10. ^cUse of antihypertensive drugs was defined as use of drugs belonging to ATC groups C03A, C07, C08, C09A/B, C09C/D, C02A, C02C and C02D. ^dUse of antithrombotic drugs was defined as use of drugs belonging to ATC group B01A. Detailed information about types of medications in use are shown in Supplementary Table S4.

Abbreviations: LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; ATC, Anatomical Therapeutic Chemical classification system.

Figure 2 Flexible calibration curve showing the agreement between quantiles of estimated risk of stroke, myocardial infarction or vascular death by the SMART-REACH model versus observed 2-year risk after recalibration.

Figure 3 Distribution of current cardiovascular disease (CVD) risk and potential benefit from optimization of all risk factors.

Notes: Distributions of (A) ten-year cardiovascular disease risk, (B) lifetime CVD risk, (C) remaining CVD-free life-years, (D) current estimated risks and treatment benefits (median (interquartile range)) from optimization of risk factors defined as systolic blood pressure ≤140 mmHg, LDL-cholesterol ≤1.8 mmol/L, smoking cessation and use of antithrombotic medication.

Abbreviation: ARR, absolute risk reduction.

Table 3 Estimated Prognosis and Benefits of Optimal Guideline-Therapy

	Total (n = 465)	Systolic Blood Pressure > 140 mmHg (n = 226)	LDL-C > 1.8 mmol/L(n = 265)	Smokers (n = 55)	No Antithrombotics (n = 10)
Current estimated risk
10-year CVD risk (%)	42 (32 to 54)	44 (34 to 54)	41 (32 to 52)	52 (39 to 66)	53 (46 to 65)
Lifetime CVD risk^a (%)	70 (63 to 76)	67 (61 to 75)	69 (63 to 75)	76 (74 to 81)	77 (68 to 84)
CVD-free life expectancy^b (years)	80.4 (76.4 to 83.5)	81.8 (78.9 to 84.3)	80.7 (76.8 to 83.6)	75.3 (72.2 to 80.1)	79.2 (75.8 to 82.3)
Remaining CVD-free life-years^c	9.9 (7.2 to 13.5)	9.5 (7.2 to 12.3)	10.0 (7.4 to 13.3)	7.6 (4.8 to 9.9)	8.1 (6.3 to 9.7)
Treatment benefits from optimal guideline therapy^d
10-year ARR (%)	6 (1 to 14)	12 (6 to 20)	9 (3 to 16)	17 (15 to 25)	17 (8 to 34)
Lifetime ARR (%)	6 (1 to 15)	14 (7 to 23)	11 (3 to 19)	15 (10 to 30)	22 (4 to 47)
Gain in CVD-free life expectancy (years)	1.4 (0.2 to 3.4)	2.6 (1.2 to 4.6)	2.0 (0.7 to 4.1)	4.4 (2.9 to 8.0)	5.1 (1.2 to 8.8)

Notes: Values are median (interquartile range). ^aDefined as risk of having an event before the 90th life-year. ^bMedian life expectancy without a CVD event or death. ^cNumber of years without a CVD-event due to current treatment. ^dDefined as systolic blood pressure 140 mmHg, LDL-C 1.8 mmol/L, smoking cessation and use of antithrombotic medications.

Abbreviations: LDL-C, Low density lipoprotein cholesterol; CVD, Cardiovascular disease; ARR, Absolute risk reduction.