CALU A29809G polymorphism in coronary atherothrombosis: Implications for coronary calcification and prognosis

Figures & data

Table I. Demographic and clinical characteristics, biomarkers, and genetic profile in non-ST-elevation acute coronary syndrome patients.

	All	Coronary angiography
Demographic and clinical data
n	374	175
Age (mean ± SD)	67.1 ± 12.7	64.2 ± 12.7
Male sex (%)	240 (64.2)	116 (66.3)
Hypercholesterolaemia (%)	165 (44.1)	97 (55.4)
Diabetes mellitus (%)	145 (38.8)	70 (40.0)
ID diabetes mellitus (%)	49 (13.1)	17 (9.7)
Hypertension (%)	276 (66.8)	114 (65.1)
Smoking habit (%)	239 (66.8)	112 (64.0)
Previous IHD (%)	199 (53.2)	76 (43.4)
Down-sloping ST (%)	137 (36.6)	74 (42.3)
TIMI risk score (median (IQR))	3 (2–4)	3 (2–4)
Previous ASA (%)	197 (52.7)	76 (43.4)
Stenosis ≥50% (%)	110 (29.4)	39 (22.3)
Biomarkers
Raised TnT levels (%)	186 (49.7)	107 (61.1)
NT-proBNP pg/mL (median (IQR))	488.2 (137.1–1879.8)	429.3 (104.7–1335.0)
Calcium score (median (IQR))	–	3 (1–6)
Low calcium score group (%)	–	58 (33.1)
High calcium score group (%)	–	117 (66.9)
Calumenin A29809G genotype
A29809A (%)	125 (33.4)	51 (29.1)
A29809G (%)	190 (50.8)	100 (57.1)
G29809G (%)	59 (15.8)	24 (13.7)

CVRF = cardiovascular risk factors; ID diabetes mellitus = insulin dependent diabetes mellitus; IHD = ischaemic heart disease; Down-sloping ST = down-sloping ST-segment at ECG; Raised TnT levels = troponin T levels are considered raised when levels were higher than 0.1 ng mL⁻¹; Previous ASA = previous acetyl salicylic acid treatment.

Table II. Association of high calcification score (≥2 points) with clinical variables, biomarkers, and genetic profile in 175 patients with coronary angiography.

	Univariate		Multivariate
	OR (95% CI)	P-value	OR (95% CI)	P-value
Clinical variables
Age ≥65 years	2.35 (1.23–4.47)	0.009	1.66 (0.73–3.76)	0.228
Sex	0.61 (0.31–1.17)	0.133	0.66 (0.28–1.57)	0.345
Hypercholesterolaemia	1.54 (0.82–2.90)	0.181	–	–
Diabetes mellitus	2.23 (1.14–4.45)	0.020	^a	–
Hypertension	2.66 (1.38–5.12)	0.004	^a	–
Smoking habit	0.72 (0.37–1.41)	0.336	–	–
Previous IHD	3.54 (1.76–7.15)	<0.001	2.65 (0.75–9.36)	0.130
Down-sloping ST	1.82 (0.94–3.52)	0.074	1.98 (0.85–4.65)	0.113
Previous ASA	2.04 (1.00–4.16)	0.051	1.33 (0.41–4.29)	0.638
Stenosis ≥50%	2.72 (1.11–6.65)	0.028	1.21 (0.33–4.21)	0.775
At least 3 CVRF	2.96 (1.50–5.85)	0.002	2.34 (1.00–5.44)	0.049
Risk symptoms	1.49 (0.74–3.00)	0.265	–	–
Biomarkers
Raised TnT	1.13 (0.59–2.16)	0.719	–	–
NT-proBNP	3.15 (1.29–7.68)	0.012	2.54 (0.92–6.98)	0.072
hs-CRP	0.74 (0.36–1.53)	0.416	–	–
Genetic profile
CALU 29809G	0.45 (0.21–0.96)	0.042	0.34 (0.14–0.84)	0.019

^aHypertension and diabetes mellitus are excluded for multivariate analysis as both of them are included in the ‘At least 3 CVRF’ variable.

CVRF = cardiovascular risk factors; IHD = ischaemic heart disease; Raised TnT = raised troponin T levels (≥ 0.1 ng mL⁻¹); Previous ASA = previous acetyl salicylic acid treatment; hs-CRP = high-sensitivity C-reactive protein.

Figure 1. A: Relationship between CALU A29809G genotype and calcification score: high calcification score patients (empty bars), low calcification score patients (full bars). B: NT-proBNP levels according with CALU A29809G genotype.

Table III. Cox regression analysis at 1- and 6-month follow-up in non-ST-elevation acute coronary syndrome patients.

	Univariate		Multivariate
	Hazard ratio	P-value	Hazard ratio	P-value
One-month follow-up (n = 353)
Risk symptoms	2.88 (1.32–6.27)	0.008	1.96 (0.86–4.49)	0.110
NT-proBNP (p75)	1.95 (0.89–4.26)	0.094	0.71 (0.30–1.68)	0.435
Down-sloping ST	2.61 (1.59–5.42)	0.011	1.97 (0.84–4.61)	0.120
CALU 29809G	0.42 (0.20–0.85)	0.017	0.42 (0.18–0.97)	0.042
Six-month follow-up (n = 350)
Age ≥65 years	2.04 (1.23–3.37)	0.006	2.13 (1.12–4.07)	0.023
Risk symptoms	2.34 (1.45–3.77)	0.001	2.01 (1.17–3.46)	0.011
NT-proBNP (p75)	2.38 (1.49–3.78)	<0.001	1.51 (0.80–2.83)	0.203
Down-sloping ST	1.80 (1.16–2.77)	0.009	1.20 (0.75–2.24)	0.353
hs-CRP (p75)	1.81 (1.39–2.88)	0.012	1.41 (0.74–2.70)	0.303
Raised TnT	1.88 (1.18–2.97)	0.008	1.12 (0.65–2.33)	0.533
CALU 29809G	0.63 (0.41–0.99)	0.043	0.59 (0.35–0.99)	0.044

TnT = Troponin T; NT-proBNP (p75) = N-terminal propeptide of the brain natriuretic peptide levels over the 75th percentile of the NT-proBNP determinations; hs-CRP (p75) = high-sensitivity C-reactive protein levels over the 75th percentile of the CRP determinations; Down-sloping ST = down-sloping ST electrocardiographic segment; Risk symptoms = severe anginal symptoms.

Figure 2. Kaplan-Meier curves showing the relationship between presence of CALU 29809G allele and cumulative event-free survival after nSTACS. A: Cumulative survival at 1-month follow-up. Log rank test, P = 0.013. B: Cumulative survival at 6-months follow-up. Log rank test, P = 0.041.