Homocysteine and the Risk of Cardiovascular Events and All-Cause Death in Elderly Population: A Community-Based Prospective Cohort Study

Figures & data

Table 1 Characteristics of the Participants by Different Serum Homocysteine Levels

Variable	Total (n=1257)	Homocysteine Level			p-value
		<15μmol/L	<30μmol/L	≥30μmol/L
		(n=601)	(n=505)	(n=151)
Age (years)	69.2±8.1	67.66±7.66	70.47±8.22*	70.79±8.33*	<0.001
Male	550 (43.8%)	203 (33.8%)	253 (50.1%)*	94 (62.3%)*	<0.001
Female	707 (56.2%)	398 (66.2%)	252 (49.9%)*	57 (37.7%)*	<0.001
Smoking	386 (30.7%)	141 (23.5%)	170 (33.7%)*	75 (49.7%)*	<0.001
Drinking	386 (30.7%)	155 (25.8%)	166 (32.9%)*	65 (43.0%)*	<0.001
Physical activity>1h/day	572 (45.5%)	284 (47.3%)	225 (44.6%)	63 (41.7%)	0.407
Dyslipidemia	736 (58.6%)	341 (56.7%)	301 (59.6%)	94 (62.3%)	0.387
Lipid-lowering therapy	35 (4.8%)	24 (7.0%)	10 (3.3%)	1 (1.1%)*	0.017
Diabetes	218 (17.3%)	120 (20.0%)	78 (15.4%)	20 (13.2%)	0.052
Hypoglycemic therapy	107 (8.5%)	71 (11.8%)	30 (5.9%)*	6 (4.0%)*	0.003
Hypertension	762 (60.6%)	357 (59.4%)	314 (62.2%)	91 (60.3%)	0.639
Antihypertensive therapy	345 (45.3%)	179 (50.1%)	124 (39.5%)	42 (46.2%)	0.151
Pulse pressure (mmHg)	62.2±17.2	60.7±16.8	63.9±17.5*	62.5±17.2	0.009
Homocysteine (µmol/l)	16.3(12.9–21.5)	12.8(10.8–14.5)	19.3(17.7–22.6)*	43.5(36.1–63.1)*	<0.001
tCholesterol (mmol/L)	5.89±1.15	5.93±1.15	5.83±1.15	5.93±1.13	0.317
Triglyceride (mmol/L)	1.31(0.97–1.88)	1.33(0.98–1.89)	1.30(0.96–1.91)	1.25(0.95–1.81)	0.889
HDL-C (mmol/L)	1.23±0.27	1.24±0.27	1.21±0.28	1.22±0.28	0.090
LDL-C (mmol/L)	2.96±0.75	3.01±0.75	2.91±0.73	2.92±0.77	0.096
Glucose (mmol/L)	5.72±1.66	5.84±1.71	5.62±1.58	5.58±1.73	0.057
hsCRP (mg/L)	0.03 (0.01–0.17)	0.02(0.01–0.08)	0.03(0.01–0.21)	0.04(0.01–0.16)*	0.004
eGFR	58.80±15.37	52.32±17.52	56.05±12.25*	53.97±12.13*	<0.001
BMI (kg/m^2)	24.07±3.91	24.23±3.78	23.96±4.07	23.82±3.92	0.383

Notes: Data are shown as mean±SD, median with IQR, or absolute number (percentage). *Compared with normal homocysteine level (<15μmol/L) statistically significant.

Abbreviations: tCholesterol, total cholesterol; HDL-C, high-density lipoprotein cholesterol-C; LDL-C, low-density lipoprotein cholesterol-C; hsCRP, high-sensitivity C-reactive protein; eGFR, estimated glomerular filtration rate (mL/min per 1.73m²); BMI, body mass index.

Table 2 Homocysteine Levels in Different Gender and Age Groups

	Homocysteine (μmol/L)			Hyperhomocysteinemia
	n	Median with IQR	p-value	n (%)	p-value
Gender	1257	16.34 (12.92–21.47)		760 (60.46)
Male	550	18.00 (14.55–24.75)*	<0.001	392 (71.27)*	<0.001
Female	707	15.27 (12.02–19.34)		368 (52.05)
Age (total)	1257
55~	185	15.14 (12.18–19.40)#	<0.001	94 (50.81)#	<0.001
60~	229	14.96 (11.55–19.58)		114 (49.78)
65~	225	15.91 (12.01–20.08)		129 (57.33)
70~	253	16.76 (13.44–21.11)		158 (62.45)
75~	241	17.99 (14.35–22.72)		174 (72.20)
≥80	124	18.82 (14.83–25.83)		91 (73.39)
Age (male)	550
55~	80	17.27 (13.49–22.85)	0.381	53 (66.25)	0.338
60~	92	16.60 (13.81–28.75)		61 (66.30)
65~	90	16.77 (14.16–20.05)		61 (67.78)
70~	118	18.09 (14.76–24.00)		86 (72.88)
75~	109	18.54 (15.22–24.94)		85 (77.98)
≥80	61	19.90 (15.28–27.74)		46 (75.41)
Age (female)	707
55~	105	13.65 (10.93–16.40)^#	<0.001	41 (39.05)^#	<0.001
60~	137	13.76 (10.88–17.97)		53 (38.69)
65~	135	15.16 (11.07–18.48)		68 (50.37)
70~	135	15.57 (12.24–19.78)		72 (53.33)
75~	132	17.22 (13.77–21.62)		89 (67.42)
≥80	63	18.24 (13.84–24.74)		45 (71.43)

Notes: Hyperhomocysteinemia, concentration of total homocysteine ≥15μmol/L. *Compared with females; ^#compared with other age groups.

Figure 1 Outcome events of 1257 participants.

Table 3 The Relationship Between Homocysteine Level and CVD Events and Death

	Homocysteine Level				HR/5μmol/L tHcy
	<15μmol/L (n=601)	<30μmol/L (n=505)	≥30μmol/L (n=151)	p trend*
CVD event (total)
Case	67	69	32
Person-year	3210.4	2549.9	778.4
Crude	1.00	1.34 (0.96–1.87)	2.18 (1.43–3.32)	<0.001	1.06 (1.03–1.09)
Model 1	1.00	1.18 (0.84–1.67)	1.93 (1.25–2.96)	0.006	1.05 (1.02–1.08)
Model 2	1.00	1.12 (0.78–1.61)	1.68 (1.06–2.67)	0.044	1.04 (1.01–1.07)
CVD event (male)
Case	20	38	19
Person-year	1025.3	1172.4	415.0
Crude	1.00	1.69 (1.01–2.90)	2.42 (1.29–4.54)	0.005	1.04 (1.01–1.08)
Model 1	1.00	1.62 (0.94–2.79)	2.38 (2.27–4.45)	0.006	1.05 (1.27–4.45)
Model 2	1.00	1.65 (0.91–3.00)	2.07 (1.01–4.26)	0.046	1.05 (1.01–1.08)
CVD event (female)
Case	47	31	13
Person-year	2012.2	1189.4	267.1
Crude	1.00	1.13 (0.72–1.77)	2.12 (1.14–3.91)	0.047	1.02 (0.96–1.08)
Model 1	1.00	0.93 (0.58–1.47)	1.62 (0.87–3.04)	0.334	1.00 (0.93–1.07)
Model 2	1.00	0.92 (0.56–1.49)	1.59 (0.83–3.04)	0.365	0.99 (0.92–1.06)
CVD death (total)
Case	20	28	14
Person-year	3150.6	2467.4	734.8
Crude	1.00	1.81 (1.01–3.20)	3.04 (1.54–6.02)	0.001	1.06 (1.01–1.10)
Model 1	1.00	1.30 (0.73–2.34)	2.21 (1.10–4.42)	0.033	1.05 (1.00–1.40)
Model 2	1.00	1.41 (0.75–2.66)	1.97 (0.95–4.29)	0.065	1.04 (0.99–1.09)
CVD death (male)
Case	6	15	9
Person-year	1061.8	1222.2	443.5
Crude	1.00	2.19 (0.85–5.66)	3.64 (1.30–10.23)	0.012	1.06 (1.01–1.11)
Model 1	1.00	1.90 (0.74–4.91)	3.51 (1.25–9.86)	0.016	1.06 (1.01–1.12)
Model 2	1.00	2.11 (0.69–6.42)	2.83 (0.78–10.21)	0.117	1.05 (0.99–1.12)
CVD death (female)
Case	14	13	5
Person-year	2088.8	1245.2	291.3
Crude	1.00	1.57 (0.74–3.34)	2.57 (0.93–7.13)	0.059	1.03 (0.93–1.13)
Model 1	1.00	0.99 (0.46–2.13)	1.34 (0.47–3.84)	0.681	0.98 (0.87–1.12)
Model 2	1.00	1.09 (0.46–2.58)	1.29 (0.41–4.09)	0.671	0.98 (0.87–1.11)
All-cause death (total)
Case	54	65	36
Person-year	3150.6	2467.4	734.8
Crude	1.00	1.56 (1.09–2.23)	2.91 (1.91–4.44)	<0.001	1.07 (1.03–1.09)
Model 1	1.00	1.10 (0.76–1.59)	2.08 (1.36–3.19)	0.003	1.06 (1.02–1.08)
Model 2	1.00	1.17 (0.79–1.73)	2.02 (1.26–3.24)	0.007	1.05 (1.01–1.07)
All-cause death (male)
Case	20	36	26
Person-year	1061.8	1222.2	443.5
Crude	1.00	1.59 (0.92–2.75)	3.20 (1.78–5.72)	<0.001	1.07 (1.03–1.09)
Model 1	1.00	1.38 (0.80–2.39)	3.11 (1.73–5.57)	<0.001	1.06 (1.03–1.09)
Model 2	1.00	1.47 (0.80–2.68)	3.08 (1.56–6.07)	0.001	1.06 (1.02–1.09)
All-cause death (female)
Case	34	29	10
Person-year	2088.8	1245.2	291.3
Crude	1.00	1.44 (0.88–2.37)	2.12 (1.05–4.28)	0.025	1.03 (0.97–1.10)
Model 1	1.00	0.87 (0.53–1.47)	1.07 (0.52–2.22)	0.954	0.98 (0.90–1.07)
Model 2	1.00	0.90 (0.41–1.98)	0.90 (0.52–1.58)	0.741	0.97 (0.89–1.06)

Notes: *Estimated using the category numbers (1, 2 and 3) as a continuous variable; CVD: cardiovascular disease; Crude: unadjusted; Model 1: adjusted for sex and age; Model 2: adjusted for sex, age, smoking, alcohol drinking, glucose, hsCRP, dyslipidemia, eGFR, pulse pressure, hypoglycemic therapy, lipid-lowering therapy and antihypertensive therapy.

Table 4 The Area Under the Curve of ROC Curve

	Conventional Risk Factors Without Hcy	Conventional Risk Factors With Hcy
Figure 2-A	0.632 (0.559–0.695)	0.649 (0.610–0.696)
Figure 2-B	0.733 (0.668–0.805)	0.739 (0.669–0.808)
Figure 2-C	0.684 (0.648–0.742)	0.699 (0.652–0.746)

Notes: Data were shown as estimate (95% CI).

Abbreviation: Hcy: homocysteine

Figure 2 Receiver-operating characteristic curves for (A) CVD events, (B) CVD death, and (C) all-cause death during 4.84-year follow-up. For each endpoint, curves are based on prediction models adjusted for conventional risk factors (sex, age, smoking, alcohol drinking, glucose, hs-CRP, dyslipidemia, eGFR, pulse pressure, hypoglycemic therapy, lipid-lowering therapy and antihypertensive therapy) with or without homocysteine (Hcy).