Methylmalonic acid, vitamin B12, and mortality risk in patients with preexisting coronary heart disease: a prospective cohort study

Table 3 The associations between declined response to B12 and mortality risk in patients with CHD

		MMA-associated mortality in Cbl subgroups		Combination of binary MMA and Cbl
		Cbl < 400 pg/ml	Cbl ≥ 400 pg/ml	MMA_low Cbl_low	MMA_low Cbl_high	MMA_high Cbl_low	MMA_high Cbl_high
Unadjusted	HR (95%CI)	1.81 (1.47–2.21)	2.95 (2.25–3.87)	1.00 (Ref)	1.00 (0.79–1.27)	2.06 (1.57–2.71)	3.57 (2.68–4.76)
Unadjusted	p value*	< 0.001	< 0.001	-	0.994	< 0.001	< 0.001
Model 1	HR (95%CI)	1.37 (1.10–1.71)	2.42 (1.91–3.06)	1.00 (Ref)	0.87 (0.72–1.05)	1.32 (1.00-1.73)	2.35 (1.87–2.96)
Model 1	p value	0.006	< 0.001	-	0.155	0.049	< 0.001
Model 2	HR (95%CI)	1.53 (1.22–1.93)	2.17 (1.70–2.78)	1.00 (Ref)	0.88 (0.72–1.09)	1.33 (1.00-1.76)	1.99 (1.48–2.66)
Model 2	p value	< 0.001	< 0.001	-	0.235	0.051	< 0.001
Model 3	HR (95%CI)	1.54 (1.21–1.95)	2.14 (1.64–2.79)	1.00 (Ref)	0.90 (0.73–1.12)	1.27 (0.95–1.69)	1.98 (1.46–2.69)
Model 3	p value	0.001	< 0.001	-	0.332	0.099	< 0.001

Ref, treating the bottom group (MMA ≤ 250 nmol/L, B12 ≤ 400 pg/mL) as the reference;
*Hazard ratio per 1 unit increases of natural log-transformed MMA; # Values are weighted hazard ratio (95% confidence interval)
Model 1: adjusted for age (years, continuous), sex (female or male), and race/ethnicity (non-Hispanic white, black, Hispanic-Mexican, or other)
Model 2: additionally adjusted for smoking status (never, ever or current), physical activity (inactive, moderate, or vigorous), body mass index (< 18.5, 18.5–25, 25–30, or ≥ 30 kg/m²), hypertension (no/yes), diabetes (no/yes), chronic obstructive pulmonary disease (no/yes), cancer (no/yes), total cholesterol (mmol/L, continuous), High-density lipoprotein cholesterol (mmol/L, continuous), C-reactive protein (mg/dL, continuous), and estimated glomerular filtration rate (ml/min/1.73 m², continuous)
Model 3: additionally adjusted for metformin use (no/yes), ACEI/ARB use (no/yes), β-blocker use (no/yes), diuretics use (no/yes), anti-lipid use (no/yes) and anti-platelet use (no/yes)

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