Table 3. Associations of Folate and Vitamin B12 Serum Levels With CVD Mortality in Various Subgroups Among Adults With Diabetes in NHANES III (1988-1994) and NHANES 2001 Through 2014.
| Characteristic | Hazard ratio (95% CIs) by quartilea | P value for interaction | |||
|---|---|---|---|---|---|
| Quartile 1 | Quartile 2 | Quartile 3 | Quartile 4 | ||
| Folate serum level, ng/mL | <7.1 | 7.1-12.1 | 12.2-19.4 | ≥19.5 | |
| Age, y | |||||
| <60 | 1.98 (0.85-4.62) | 1 [Reference] | 1.19 (0.54-2.66) | 0.97 (0.34-2.72) | .76 |
| ≥60 | 1.22 (0.91-1.65) | 1 [Reference] | 1.12 (0.83-1.51) | 1.20 (0.87-1.66) | |
| Sex | |||||
| Female | 1.14 (0.77-1.69) | 1 [Reference] | 0.77 (0.50-1.17) | 0.77 (0.48-1.25) | .82 |
| Male | 1.78 (1.17-2.71) | 1 [Reference] | 1.55 (1.05-2.29) | 1.32 (0.83-2.08) | |
| Race and ethnicity | |||||
| Non-Hispanic White | 1.36 (0.90-2.05) | 1 [Reference] | 0.98 (0.68-1.42) | 0.93 (0.65-1.34) | .35 |
| Otherb | 1.97 (1.28-3.01) | 1 [Reference] | 1.79 (1.19-2.70) | 1.40 (0.82-2.40) | |
| BMI | |||||
| <30 | 1.73 (1.03-2.88) | 1 [Reference] | 1.21 (0.76-1.93) | 0.72 (0.42-1.23) | .96 |
| ≥30 | 1.85 (0.89-3.85) | 1 [Reference] | 1.59 (0.93-2.71) | 1.87 (1.04-3.37) | |
| Smoking status | |||||
| Never | 1.37 (0.84-2.24) | 1 [Reference] | 1.34 (0.81-2.22) | 1.07 (0.66-1.73) | .21 |
| Ever or current | 1.56 (1.09-2.23) | 1 [Reference] | 1.08 (0.72-1.60) | 1.02 (0.63-1.67) | |
| Alcohol consumption | |||||
| Nondrinker | 1.37 (0.98-1.92) | 1 [Reference] | 1.11 (0.78-1.59) | 0.83 (0.53-1.30) | .82 |
| Drinker | 1.57 (0.90-2.76) | 1 [Reference] | 1.29 (0.84-1.98) | 1.28 (0.81-2.04) | |
| Diabetes duration, y | |||||
| <10 | 1.76 (0.93-3.35) | 1 [Reference] | 1.29 (0.80-2.09) | 0.83 (0.48-1.44) | .17 |
| ≥10 | 1.51 (0.69-3.31) | 1 [Reference] | 1.43 (0.83-2.47) | 1.50 (0.75-3.00) | |
| Physical activity | |||||
| Inactive | 1.53 (0.94-2.49) | 1 [Reference] | 1.27 (0.79-2.04) | 1.11 (0.66-1.86) | .30 |
| Active | 2.41 (0.89-6.54) | 1 [Reference] | 1.79 (0.98-3.29) | 1.29 (0.54-3.08) | |
| HbA1c, % | |||||
| <7.0 | 1.18 (0.62-2.24) | 1 [Reference] | 1.05 (0.63-1.75) | 0.91 (0.61-1.35) | .02 |
| ≥7.0 | 2.65 (1.46-4.81) | 1 [Reference] | 1.80 (1.12-2.91) | 1.46 (0.66-3.23) | |
| Hypertension | |||||
| Yes | 1.84 (1.06-3.20) | 1 [Reference] | 1.37 (0.85-2.19) | 1.47 (0.91-2.36) | .33 |
| No | 1.97 (1.03-3.78) | 1 [Reference] | 1.49 (0.74-3.03) | 0.74 (0.30-1.79) | |
| Hypercholesterolemia | |||||
| Yes | 2.55 (1.28-5.08) | 1 [Reference] | 1.73 (1.02-2.95) | 1.56 (0.82-2.97) | .16 |
| No | 1.27 (0.69-2.33) | 1 [Reference] | 1.19 (0.70-2.03) | 0.85 (0.47-1.55) | |
| Vitamin B12 serum level, pg/mL | <369.1 | 369.1-506.0 | 506.1-703.4 | ≥703.5 | |
| Age, y | |||||
| <60 | 1.13 (0.74-1.73) | 1 [Reference] | 1.78 (1.13-2.81) | 1.71 (1.05-2.77) | .48 |
| ≥60 | 1.07 (0.91-1.25) | 1 [Reference] | 1.10 (0.86-1.40) | 1.14 (0.92-1.41) | |
| Sex | |||||
| Female | 1.09 (0.83-1.44) | 1 [Reference] | 1.42 (1.06-1.89) | 1.23 (0.88-1.70) | .75 |
| Male | 1.11 (0.86-1.43) | 1 [Reference] | 1.30 (0.94-1.79) | 1.36 (1.01-1.82) | |
| Race and ethnicity | |||||
| Non-Hispanic White | 1.01 (0.83-1.22) | 1 [Reference] | 1.43 (1.08-1.88) | 1.27 (0.94-1.71) | .97 |
| Otherb | 1.48 (1.09-2.01) | 1 [Reference] | 1.28 (0.95-1.71) | 1.40 (0.99-1.98) | |
| BMI | |||||
| <30 | 0.87 (0.66-1.13) | 1 [Reference] | 1.11 (0.84-1.48) | 1.19 (0.89-1.59) | .53 |
| ≥30 | 1.33 (1.01-1.76) | 1 [Reference] | 1.59 (1.18-2.15) | 1.29 (0.93-1.80) | |
| Smoking status | |||||
| Never | 1.08 (0.79-1.48) | 1 [Reference] | 1.44 (1.05-1.97) | 1.34 (0.95-1.89) | .85 |
| Ever or current | 1.15 (0.91-1.45) | 1 [Reference] | 1.36 (1.01-1.83) | 1.25 (0.95-1.66) | |
| Alcohol consumption | |||||
| Nondrinker | 1.15 (0.91-1.46) | 1 [Reference] | 1.40 (1.06-1.85) | 1.19 (0.91-1.56) | .17 |
| Drinker | 1.06 (0.80-1.41) | 1 [Reference] | 1.33 (0.97-1.81) | 1.29 (0.92-1.80) | |
| Diabetes duration, y | |||||
| <10 | 1.18 (0.92-1.50) | 1 [Reference] | 1.46 (1.13-1.90) | 1.54 (1.15-2.07) | .58 |
| ≥10 | 1.07 (0.80-1.44) | 1 [Reference] | 1.29 (0.92-1.81) | 1.09 (0.80-1.48) | |
| Physical activity | |||||
| Inactive | 1.24 (1.00-1.54) | 1 [Reference] | 1.51 (1.20-1.90) | 1.42 (1.14-1.77) | .97 |
| Active | 0.86 (0.62-1.20) | 1 [Reference] | 1.19 (0.83-1.72) | 1.18 (0.81-1.71) | |
| HbA1c, % | |||||
| <7.0 | 1.97 (1.12-3.46) | 1 [Reference] | 1.67 (1.00-2.79) | 2.93 (1.65-5.21) | .94 |
| ≥7.0 | 1.53 (0.81-2.91) | 1 [Reference] | 1.69 (0.90-3.16) | 1.79 (1.06-3.04) | |
| Hypertension | |||||
| Yes | 1.47 (0.92-2.33) | 1 [Reference] | 1.52 (0.93-2.51) | 1.94 (1.19-3.16) | .80 |
| No | 2.55 (1.15-5.67) | 1 [Reference] | 2.24 (1.05-4.80) | 3.73 (1.73-8.08) | |
| Hypercholesterolemia | |||||
| Yes | 1.05 (0.82-1.35) | 1 [Reference] | 1.38 (1.00-1.91) | 0.90 (0.68-1.19) | .29 |
| No | 1.15 (0.88-1.50) | 1 [Reference] | 1.37 (1.06-1.78) | 1.85 (1.39-2.46) | |
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); CVD, cardiovascular disease; HbA1c, glycated hemoglobin A1c; NHANES, National Health and Nutrition Examination Survey.
SI conversion factors: To convert serum levels of vitamin B12 to picomoles per liter, multiply by 0.7378; folate to nanomoles per liter, multiply by 2.266; and HbA1c levels to a proportion of total hemoglobin, multiply by 0.01.
Adjusted for age (continuous), sex (male or female), race and ethnicity (Mexican American, non-Hispanic Black, non-Hispanic White, or other), BMI (<25.0, 25.0-29.9, or ≥30.0), educational level (<high school, high school or equivalent, or ≥college), family income level (lower, normal, or higher), smoking status (never, ever, or current), alcohol consumption (none, low to moderate, or heavy), physical activity (inactive or active), Healthy Eating Index (continuous), duration of diabetes (<3, 3-10, or >10 years), diabetes medication use (none, only oral glucose-lowering medication, only insulin, or oral medication and insulin), HbA1c (<7% or ≥7%), self-reported hypertension (yes or no), and self-reported hypercholesterolemia (yes or no). The strata variable was not included when stratifying by itself.
Categorized based on self-report in the NHANES interview.