Abstract P016: Plasma Retinol-binding Protein 4 Levels and Risk of Coronary Heart Disease in US Women
Authors: Sun Qi , Shi Ling , Kiernan Urban A , Phillips David A , Kahn Barbara B , Hu Frank B , Manson JoAnn E , Albert Christine M , Rexrode Kathryn M 
Published: July 2021

Background:
Retinol-binding protein 4 (RBP4) may play an important role in the etiology of insulin resistance and metabolic syndrome. Few data are available on the relationship between RBP4 and coronary heart disease (CHD). Further, previous studies did not distinguish among full-length and truncated forms of RBP4 that may have various biological activities.

Methods and Results:
We measured plasma levels of full-length and several truncated sub-fractions of RBP4 (RBP4-L, RBP4-LL, and RBP4-RNLL) by mass spectrometry among 474 incident fatal or non-fatal coronary heart disease patients and 472 matched controls who were identified and selected in the Nurses’ Health Study cohort during 16 years of follow-up (1990-2006). After multivariate adjustment for covariates, including age, smoking, body mass index, and dietary factors, higher levels of full-length RBP4 were associated with moderately increased risk of total CHD. The odds ratio (OR) comparing extreme quintiles of full-length RBP4 levels was 1.76 (95% CI: 0.98, 3.15; P for trend = 0.04) for total CHD. These associations were attenuated after further adjustment of history of hypertension, glomerular filtration rate, total cholesterol, and triacylglycerol that might mediate the effects of RBP4 on CHD risk: the odds ratio (95% confidence interval) was 1.48 (0.79, 2.77; P for trend = 0.16). Associations for truncated and total RBP4 levels were not significant (Table 1).

Conclusion:
In this cohort of women, higher circulating full-length RBP4 levels are modestly associated with risk of CHD. More data are warranted to confirm the current findings.

Table 1.

Relative risk (95% CI) of coronary heart disease (CHD) associated with RBP4 levels, the Nurses’ Health Study

Quintiles of RBP4 levels (μ g/mL)
P for trend

1 (lowest)
3
5 (highest)

Full-length RBP4

Model 1
*

1.0
1.30 (0.83, 2.04)
1.58 (0.94, 2.67)
0.07

Model 2
†

1.0
1.23 (0.74, 2.03)
1.76 (0.98, 3.15)
0.04

Model 3
‡

1.0
1.13 (0.66, 1.93)
1.48 (0.79, 2.77)
0.16

Total truncated RBP4
§

Model 1
*

1.0
1.06 (0.69, 1.63)
1.27 (0.82, 1.97)
0.26

Model 2
†

1.0
0.90 (0.56, 1.45)
1.42 (0.87, 2.34)
0.07

Model 3
‡

1.0
0.83 (0.49, 1.40)
1.30 (0.74, 2.26)
0.18

Total RBP4

Model 1
*

1.0
1.28 (0.82, 1.99)
1.55 (0.95, 2.52)
0.11

Model 2
†

1.0
1.26 (0.77, 2.06)
1.68 (0.97, 2.91)
0.05

Model 3
‡

1.0
1.05 (0.62, 1.77)
1.31 (0.72, 2.39)
0.26

*

Model 1 was adjusted for the matching factors: age at blood draw, smoking status, fasting status, and time of blood drawing.

†

Based on model 1, model 2 was further adjusted for body mass index, postmenopausal status, hormone use, physical activity, alcohol use, parental history of MI before age 65 years, history of hypercholesterolemia or diabetes, use of aspirin, and intakes of whole grains, trans fat, and polyunsaturated fat.

‡

Based on model 2, model 3 was further adjusted for history of hypertension, glomerular filtration rate, total cholesterol, and triacylglycerol levels.

§

Total truncated RBP4 levels equal the sum of levels of RBP4-L, RBP4-LL, and RBP4-RNLL.