Preventive cardiology
Red Blood Cell Membrane Concentration of cis-Palmitoleic and cis-Vaccenic Acids and Risk of Coronary Heart Disease

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Although previous studies have suggested associations between plasma palmitoleic acid and coronary heart disease (CHD) risk factors, including blood pressure, inflammation, and insulin resistance, little is known about the relation of palmitoleic acid and CHD. This ancillary study of the Physicians' Health Study was designed to examine whether red blood cell (RBC) membrane cis-palmitoleic acid and cis-vaccenic acid—2 fatty acids that can be synthesized endogenously—are associated with CHD risk. We used a risk set sampling method to prospectively select 1,000 incident CHD events and 1,000 matched controls. RBC membrane fatty acids were measured using gas chromatography. The CHD cases were ascertained using an annual follow-up questionnaire and validated by an End Point Committee through a review of the medical records. In a conditional logistic regression analysis adjusting for demographics, anthropometric, lifestyle factors, and co-morbidity, the odds ratios and 95% confidence intervals (CIs) for CHD were 1.0 (referent), 1.29 (95% CI 0.95 to 1.75), 1.08 (95% CI 0.78 to 1.51), 1.25 (95% CI 0.90 to 1.75), and 1.48 (95% CI 1.03 to 2.14) across consecutive quintiles of RBC membrane cis-palmitoleic acid (p for trend = 0.041). The odds ratio associated with each SD higher RBC membrane cis-palmitoleic acid level was 1.19 (95% CI 1.06 to 1.35) in a multivariate-adjusted model. Finally, RBC membrane cis-vaccenic acid was inversely associated with CHD risk (odds ratio 0.79, 95% CI 0.69 to 0.91, per SD increase). In conclusion, our data showed a positive association between RBC membrane cis-palmitoleic acid and CHD risk in male physicians. Furthermore, RBC membrane cis-vaccenic acid was inversely related to CHD.

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Methods

The participants in these analyses were members of the Physicians Health Study (PHS) I and II who provided blood samples from 1995 to 2001. The PHS I is a completed randomized trial designed to study the effects of low-dose aspirin and β-carotene on cardiovascular disease and cancer.16 The PHS II is a randomized trial (started in 1997) designed to study the effects of various vitamins on the risk of cardiovascular disease and cancer.17

In the present ancillary study, we used a prospective nested

Results

The mean age ± SD was 68.7 ± 8.7 years (range 50.4 to 92.0) among the 2,000 study participants. In the control series, the median RBC concentration of cis-palmitoleic and cis-vaccenic acids was 0.49% (interquintile range 0.37% to 0.65%) and 1.69% (interqintile range 1.47% to 2.00%) of the total RBC membrane fatty acid levels, respectively. Compared to those in the lowest quintile, those with a higher quintile of cis-palmitoleic acid had a greater body mass index; greater energy intake; greater

Discussion

In the present prospective nested case-control ancillary study of United States male physicians, we observed a positive association between RBC cis-palmitoleic acid and the 16:1n7/16:0 ratio with CHD risk. Furthermore, RBC cis-vaccenic acid and elongase activity were inversely associated with CHD risk. These findings were robust after additional adjustment of alcohol consumption and energy from carbohydrate and protein—factors that stimulate hepatic DNL.

Limited data are available on the

Acknowledgment

We are indebted to the participants in the Physicians Health Study (PHS) for their outstanding commitment and cooperation and to the entire PHS staff for their expert and unfailing assistance.

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  • Cited by (0)

    The present ancillary study was funded by grant R21HL088081 (to L. Djousse) from the National Heart, Lung, and Blood Institute (Bethesda, Maryland). The Physicians' Health Study is supported by grants CA-34944, CA-40360, and CA-097193 from the National Cancer Institute (Bethesda, Maryland) and grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute (Bethesda, Maryland).

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