Repeated versus single measurement of plasma omega 3 fatty acids and risk of heart failure

Purpose Studies have previously examined the relation between a single measure of plasma fatty acids and risk of heart failure. However, it is unclear whether the use of
repeated measures of fatty acids over time is required for the assessment of omega 3 fatty acids heart failure relation. Methods Using a nested case control design, this ancillary study used 421 cases and 421 matched controls from the Physicians’ Health Study to assess the variability of plasma phospholipid fatty acids over time and compare the results of omega 3 fatty acids heart failure associations using a single versus repeated measurements of plasma phospholipid fatty acids. Plasma omega 3 fatty acids were measured at baseline (1982) and approximately 15 years later using gas chromatography. Results Spearman’s correlation coefficients between baseline and follow up measures of alpha linolenic acid (ALA), EPA, DPA, and DHA were 0.20, 0.45, 0.28, and 0.50, respectively, in the control series. Multivariable adjusted odds ratios for heart failure per standard deviation higher plasma ALA were 0.98 (95  per cent  CI 0.85 to 1.13) when using baseline ALA and 0.86 (95  per cent CI 0.74 to 1.01) when using the average of baseline and follow up ALA measurements. Corresponding odds ratios for total long chain omega 3 FAs were 0.87 (0.73 to 1.03) and 0.88 (0.75 to 1.04).
Conclusions Our data demonstrate modest correlation between measurements of plasma phospholipid fatty acids spaced by 15 years. A single measurement of plasma
phospholipid fatty acids appears reasonable to estimate the risk of heart failure over long term follow up. (Authors abstract)

Heart failure (HF) is still a major public health burden in the USA with high mortality. Due to costs and logistical issues associated with measuring blood FAs in a large number of subjects, a common limitation of previous observational studies has been the use of a single measurement of plasma or red blood cell membrane fatty acids. Plasma or red blood cell membrane fatty acid composition can change with dietary patterns and metabolism over time, thereby raising the question as to whether a single measure of plasma fatty acids is appropriate in epidemiologic studies.  Non differential exposure misclassification during follow up may bias the results toward the null. Because it is expensive to measure fatty acid profiles, it is important to know whether repeated measures of plasma fatty acids are necessary to make a valid inference on the relation of fatty acids with outcomes of interest. A previous study assessing long term reliability of plasma phospholipid measurement utilized two samples obtained approximately 3 years apart from 50 subjects and found correlation coefficients ranging from 0.35 to 0.51 for omega 3 FAs.  Therefore, the present study sought to assess variability of plasma phospholipid fatty acids on blood samples collected 15 years apart. In addition, the study determined whether the relation of omega 3 fatty acids with HF using a single baseline measurement of omega 3 fatty acids was comparable to results obtained using the average of two measurements of omega 3 fatty acids obtained at baseline and at about 15 years later during follow up among US male physicians. In this cohort of US male physicians, a modest correlation between individual plasma phospholipid fatty acids measured on blood samples collected 15 years apart was observed.  In addition, use of single measurement or mean FAs obtained on blood samples collected 15 years apart yielded similar conclusions on the relation of FAs with HF.  The data demonstrate a reasonable correlation between two assessments of FAs spaced by 15 years. In addition, when compared to repeated measurements, a single measurement of plasma phospholipids fatty acids appears appropriate to estimate the risk of HF over long term follow up. (Editors comments)