High-sensitivity C-reactive protein and exercise-induced changes in subjects suspected of coronary artery disease

Figures & data

Figure 1 Flow diagram illustrating the inclusion process.

Note: CAD50 refers to subjects with ≥50% coronary artery lumen diameter stenosis.

Abbreviations: ET, exercise test; CAD, coronary artery disease; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; hs-CRP, high-sensitivity C-reactive protein; CTCA, computed tomography coronary angiography.

Table 1 Baseline variables in all study subjects and divided in non-CAD and CAD50 subjects

Variables	All subjects n=155	Non-CAD n=114	CAD50 n=41	P-value
Age, years, mean ± SD	58.3±11.7	55.6±11.2	65.9±9.6	<0.0001
Male sex, n (%)	95 (61.3)	61 (53.5)	34 (82.9)	0.001
BMI, kg/m^2 ± SD	26.9±4.2	26.7±4.4	27.3±3.9	NS
Waist circumference, cm, mean ± SD	98.5±12.4	97.1±12.2	102.2±12.4	<0.05
Waist–hip ratio, mean ± SD	0.93±0.08	0.92±0.08	0.98±0.07	0.0001
Hs-CRP, mg/L, median (IQR)	1.53 (0.83–3.57)	1.30 (0.76–2.74)	2.93 (1.03–5.06)	0.007
Delta hs-CRP, median (IQR)	0.13 (0.05–0.24)	0.12 (0.05–0.24)	0.17 (0.07–0.29)	NS
Risk factors
Diabetes, n (%)	17 (11.0)	8 (7.0)	9 (22.0)	0.02
Former or current smoker, n (%)	113 (72.9)	83 (72.8)	30 (73.2)	NS
Hypercholesterolemia, n (%)	57 (36.8)	38 (33.3)	19 (46.3)	NS
Hypertension, n (%)	72 (46.5)	46 (40.4)	26 (63.4)	0.02
Family history of early CAD, n (%)	43 (27.7)	27 (23.7)	16 (39.0)	NS
Symptoms
Typical/atypical angina, n (%)	38 (24.5)	13 (11.4)	25 (61.0)	<0.0001
Noncardiac chest pain, n (%)	117 (75.5)	101 (88.6)	16 (39.0)	<0.0001
Medication
Aspirin, n (%)	52 (35.1)	27 (25.2)	25 (61.0)	<0.0001
β-blockers, n (%)	25 (16.9)	17 (15.9)	8 (19.5)	NS
Nitrates, n (%)	5 (3.4)	2 (1.9)	3 (7.3)	NS
Calcium antagonists, n (%)	28 (18.9)	16 (15.0)	12 (29.3)	NS

Notes: Data are presented as mean ± SD, median (IQR), or n (%). CAD50 refers to subjects with ≥50% coronary artery lumen diameter stenosis.

Abbreviations: CAD, coronary artery disease; SD, standard deviation; BMI, body mass index; NS, nonsignificant; hs-CRP, high-sensitivity C-reactive protein; IQR, interquartile range.

Table 2 Stress test results in all study subjects and divided in non-CAD and CAD50 subjects

	All subjects n=155	Non-CAD n=114	CAD50 n=41	P-value
Pretest probability, % ± SD	37.0±25.2	28.1±19.5	61.7±22.8	<0.0001
Stress test performance
Duration, minutes ± SD	9.3±3.7	9.3±3.7	9.3±3.4	NS
Maximum workload, METS ± SD	8.4±2.9	8.9±3.0	7.2±1.9	0.001
Peak HR, beats/minute ± SD	149.3±22.1	152.6±22.0	140.1±19.9	0.002
% of max predicted HR, % ± SD	92.0±11.2	92.6±11.2	90.5±11.3	NS
Subjects reaching 85% of max predicted HR, n (%)	123 (79.4)	93 (81.6)	30 (73.2)	NS
Peak SBP, mmHg ± SD	193.8±30.9	192.7±30.9	196.9±28.4	NS
Reason for termination of test
Exhaustion, n (%)	104 (67.1)	76 (66.7)	28 (68.3)	NS
Angina, n (%)	4 (2.6)	0 (0)	4 (9.8)	<0.001
Muscular weakness, n (%)	23 (14.8)	18 (15.8)	5 (12.2)	NS
Dyspnea, n (%)	20 (12.9)	17 (14.9)	3 (7.3)	NS
Arrhythmia, n (%)	4 (2.6)	3 (2.6)	1 (2.4)	NS
Angina				<0.0001
No, n (%)	127 (81.9)	103 (90.4)	24 (58.5)
Nonlimiting, n (%)	24 (15.5)	11 (9.7)	13 (31.7)
Limiting, n (%)	4 (2.6)	0 (0.0)	4 (9.8)
ST depression (mV)				0.10
0.0, n (%)	114 (73.6)	88 (77.2)	26 (63.4)
≥1.0, n (%)	41 (26.5)	26 (22.8)	15 (36.6)
Conclusion of the ET				0.04
Conclusive negative ET, n (%)	88 (56.1)	71 (61.2)	17 (41.5)
Inconclusive ET, n (%)	22 (14.2)	16 (14.0)	6 (14.6)
Positive ET, n (%)	45 (28.7)	27 (23.3)	18 (43.9)
ET protocol used				<0.001
25 watts/25 watts/2 minutes, n (%)	119 (76.8)	79 (69.3)	40 (97.6)
50 watts/50 watts/2 minutes, n (%)	36 (23.2)	35 (30.7)	1 (2.4)

Notes: Data are presented as mean ± SD, or n (%). CAD50 refers to subjects with ≥50% coronary artery lumen diameter stenosis.

Abbreviations: CAD, coronary artery disease; SD, standard deviation; MET, metabolic equivalent; HR, heart rate; SBP, systolic blood pressure at rest; ET, exercise test.

Table 3 Multivariate linear regression analysis with Ln hs-CRP as dependent variable

	Outcome Ln hs-CRP
	Coefficient	95% CI	P-value
Daily life activity level	−0.167	−0.311 to −0.023	0.023
BMI	0.047	0.011–0.082	0.010
Ln hs-TnT	0.513	0.306–0.721	<0.001

Notes: Cholesterol, cigarette smoking, diabetes, sex, age, left ventricular ejection fraction, estimated glomerular filtration rate, waist circumference, waist–hip ratio, and CAD50/CAD70 were tested in the model but excluded because P-value>0.1.

Abbreviations: Ln, natural logarithm; hs, high-sensitivity; CRP, C-reactive protein; CI, confidence interval; BMI, body mass index; TnT, troponin T.

Figure 2 Box plots showing median hs-CRP levels.

Notes: Shown are subjects with hs-TnT ≤3.00 pg/ml (n=79), subjects with hs-TnT levels between 3.00 and 7.26 pg/ml (n=38), and subjects with very high hs-TnT levels >7.26 pg/ml (n=38).

Abbreviations: hs, high-sensitivity; CRP, C-reactive protein; TnT, troponin T.

Table 4 Multivariate logistic regression analysis with CAD50 as dependent variable

	Outcome CAD50
	Odds ratio	95% CI	P-value
Hs-CRP	2.32	0.95–5.69	0.065
Age	1.10	1.05–1.15	<0.001
Male sex	5.96	2.11–16.83	0.001
Diabetes	3.97	1.19–13.30	0.025

Notes: Hs-CRP was dichotomized at 2.93 mg/L. Cholesterol, estimated glomerular filtration rate, cigarette smoking, BMI, waist circumference, waist–hip ratio, daily physical activity level, systolic blood pressure, left ventricular ejection fraction, and ventricular hypertrophy were tested in the model but excluded because of P-value>0.1.

Abbreviations: CAD, coronary artery disease; hs-CRP, high-sensitivity C-reactive protein; CI, confidence interval; BMI, body mass index.

Figure 3 Box plots illustrating baseline hs-CRP in non-CAD subjects and CAD50 subjects.

Note: CAD50 refers to subjects with ≥50% coronary artery lumen diameter stenosis.

Abbreviations: hs-CRP, high-sensitivity C-reactive protein; CAD, coronary artery disease.

Figure 4 Receiver operating curve illustrating baseline hs-CRP and CAD50.

Note: CAD50 refers to subjects with ≥50% coronary artery lumen diameter stenosis.

Abbreviations: ROC, receiver operating characteristic; hs-CRP, high-sensitivity C-reactive protein; CAD, coronary artery disease.

Figure 5 Median hs-CRP values in study subjects grouped in four groups.

Notes: The four groups are: no calcification in coronary arteries (n=64); calcifications without stenosis (n=50); CAD with 50%–70% stenosis (n=16); and CAD with ≥70% stenosis (n=25).

Abbreviations: hs-CRP, high-sensitivity C-reactive protein; CAD, coronary artery disease.