Table 2.
Relative Risk of Cardiovascular Mortality and Incident Cardiovascular Disease According to Plasma Phospholipid n-6 Polyunsaturated Fatty Acids among 2792 US Adults.
| Multivariable hazard ratio (95% CI), by quintiles of plasma phospholipid fatty acid levels* | ||||||
|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | Ptrend† | |
| Total Cardiovascular Mortality (678 cases)‡ | ||||||
| LA | 1.0 (Reference) | 0.88 (0.69, 1.12) | 0.84 (0.66, 1.07) | 0.69 (0.53, 0.90) | 0.78 (0.60, 1.01) | 0.02 |
| AA | 1.0 (Reference) | 0.92 (0.72, 1.18) | 1.20 (0.95, 1.52) | 1.04 (0.81, 1.33) | 1.00 (0.78, 1.30) | 0.70 |
| GLA | 1.0 (Reference) | 0.87 (0.68, 1.10) | 1.02 (0.81, 1.30) | 0.89 (0.70, 1.14) | 0.99 (0.78, 1.27) | 0.89 |
| DGLA | 1.0 (Reference) | 0.85 (0.66, 1.08) | 0.89 (0.70, 1.14) | 0.74 (0.57, 0.96) | 0.94 (0.73, 1.20) | 0.55 |
| Total CHD Mortality (427 cases) | ||||||
| LA | 1.0 (Reference) | 0.98 (0.72, 1.34) | 0.96 (0.71, 1.30) | 0.78 (0.57, 1.08) | 0.80 (0.57, 1.12) | 0.09 |
| AA | 1.0 (Reference) | 0.95 (0.70, 1.30) | 1.09 (0.81, 1.48) | 1.11 (0.82, 1.50) | 0.97 (0.70, 1.34) | 0.87 |
| GLA | 1.0 (Reference) | 0.91 (0.67, 1.24) | 1.11 (0.83, 1.50) | 0.93 (0.68, 1.27) | 1.11 (0.82, 1.51) | 0.46 |
| DGLA | 1.0 (Reference) | 0.90 (0.66, 1.21) | 0.90 (0.67, 1.23) | 0.73 (0.52, 1.02) | 1.02 (0.75, 1.39) | 0.94 |
| Arrhythmic CHD mortality (225 cases)§ | ||||||
| LA | 1.0 (Reference) | 1.27 (0.82, 1.96) | 1.14 (0.73, 1.77) | 1.30 (0.84, 2.02) | 1.22 (0.76, 1.95) | 0.44 |
| AA | 1.0 (Reference) | 1.25 (0.81, 1.92) | 1.29 (0.84, 1.98) | 1.19 (0.77, 1.85) | 0.95 (0.60, 1.52) | 0.78 |
| GLA | 1.0 (Reference) | 0.79 (0.52, 1.19) | 0.91 (0.60, 1.36) | 0.78 (0.51, 1.19) | 0.96 (0.63, 1.46) | 0.99 |
| DGLA | 1.0 (Reference) | 0.82 (0.54, 1.22) | 0.85 (0.57, 1.28) | 0.59 (0.37, 0.93) | 0.85 (0.55, 1.30) | 0.31 |
| Non-arrhythmic CHD mortality (202 cases)§ | ||||||
| LA | 1.0 (Reference) | 0.75 (0.49, 1.16) | 0.79 (0.52, 1.20) | 0.42 (0.26, 0.69) | 0.51 (0.32, 0.82) | 0.001 |
| AA | 1.0 (Reference) | 0.70 (0.44, 1.11) | 0.92 (0.60, 1.41) | 1.04 (0.68, 1.60) | 1.00 (0.64, 1.56) | 0.60 |
| GLA | 1.0 (Reference) | 1.09 (0.69, 1.72) | 1.41 (0.91, 2.20) | 1.17 (0.73, 1.89) | 1.33 (0.83, 2.11) | 0.28 |
| DGLA | 1.0 (Reference) | 1.04 (0.65, 1.65) | 1.00 (0.63, 1.60) | 0.94 (0.58, 1.53) | 1.29 (0.81, 2.05) | 0.31 |
| Congestive Heart Failure mortality§ (84 cases) | ||||||
| LA | 1.0 (Reference) | 0.81 (0.40, 1.65) | 0.88 (0.45, 1.70) | 0.45 (0.21, 0.97) | 0.55 (0.26, 1.16) | 0.05 |
| AA | 1.0 (Reference) | 1.01 (0.51, 1.99) | 1.12 (0.57, 2.20) | 1.27 (0.65, 2.50) | 0.93 (0.44, 1.97) | 0.91 |
| GLA | 1.0 (Reference) | 1.12 (0.54, 2.33) | 1.57 (0.78, 3.15) | 1.48 (0.73, 3.04) | 1.47 (0.70, 3.08) | 0.28 |
| DGLA | 1.0 (Reference) | 1.29 (0.62, 2.69) | 1.81 (0.91, 3.62) | 0.95 (0.43, 2.12) | 1.23 (0.57, 2.66) | 0.95 |
| Other non-arrhythmic CHD mortality§ (118 cases) | ||||||
| LA | 1.0 (Reference) | 0.71 (0.41, 1.24) | 0.75 (0.44, 1.29) | 0.41 (0.22, 0.78) | 0.49 (0.26, 0.91) | 0.009 |
| AA | 1.0 (Reference) | 0.49 (0.26, 0.94) | 0.81 (0.46, 1.42) | 0.88 (0.51, 1.54) | 0.99 (0.57, 1.73) | 0.63 |
| GLA | 1.0 (Reference) | 1.06 (0.59, 1.93) | 1.31 (0.74, 2.32) | 0.96 (0.52, 1.77) | 1.21 (0.66, 2.19) | 0.68 |
| DGLA | 1.0 (Reference) | 0.92 (0.50, 1.68) | 0.60 (0.31, 1.18) | 0.94 (0.51, 1.73) | 1.34 (0.75, 2.39) | 0.19 |
| Stroke Mortality (154 cases) | ||||||
| LA | 1.0 (Reference) | 0.76 (0.45, 1.30) | 0.76 (0.45, 1.28) | 0.55 (0.31, 0.97) | 0.80 (0.47, 1.37) | 0.35 |
| AA | 1.0 (Reference) | 1.00 (0.60, 1.67) | 1.23 (0.76, 2.00) | 1.07 (0.64, 1.81) | 1.05 (0.61, 1.80) | 0.77 |
| GLA | 1.0 (Reference) | 0.74 (0.45, 1.24) | 0.87 (0.53, 1.43) | 0.89 (0.54, 1.46) | 0.90 (0.54, 1.50) | 0.99 |
| DGLA | 1.0 (Reference) | 0.80 (0.48, 1.34) | 1.11 (0.68, 1.81) | 0.93 (0.55, 1.57) | 0.93 (0.55, 1.56) | 0.94 |
| Total fatal and nonfatal CHD (720 cases)‖ | ||||||
| LA | 1.0 (Reference) | 0.99 (0.77, 1.27) | 1.11 (0.88, 1.41) | 1.03 (0.81, 1.32) | 0.98 (0.76, 1.27) | 0.95 |
| AA | 1.0 (Reference) | 0.98 (0.78, 1.24) | 1.00 (0.80, 1.27) | 1.09 (0.86, 1.37) | 0.89 (0.69, 1.14) | 0.59 |
| GLA | 1.0 (Reference) | 1.02 (0.81, 1.29) | 1.19 (0.94, 1.50) | 1.05 (0.83, 1.34) | 1.16 (0.91, 1.47) | 0.28 |
| DGLA | 1.0 (Reference) | 0.91 (0.72, 1.16) | 0.89 (0.70, 1.13) | 0.84 (0.65, 1.08) | 1.07 (0.84, 1.37) | 0.57 |
| Nonfatal myocardial infarction (418 cases) | ||||||
| LA | 1.0 (Reference) | 1.02 (0.73, 1.43) | 1.39 (1.02, 1.90) | 1.22 (0.88, 1.69) | 1.19 (0.84, 1.67) | 0.23 |
| AA | 1.0 (Reference) | 0.96 (0.71, 1.30) | 0.87 (0.64, 1.18) | 1.11 (0.83, 1.50) | 0.87 (0.63, 1.20) | 0.65 |
| GLA | 1.0 (Reference) | 1.13 (0.83, 1.55) | 1.32 (0.96, 1.80) | 1.28 (0.93, 1.75) | 1.18 (0.85, 1.64) | 0.36 |
| DGLA | 1.0 (Reference) | 0.94 (0.68, 1.29) | 0.95 (0.69, 1.30) | 1.01 (0.73, 1.40) | 1.14 (0.83, 1.57) | 0.29 |
| Total fatal and nonfatal stroke (463 cases)# | ||||||
| LA | 1.0 (Reference) | 0.96 (0.71, 1.30) | 1.00 (0.74, 1.36) | 0.87 (0.64, 1.19) | 0.92 (0.67, 1.27) | 0.50 |
| AA | 1.0 (Reference) | 1.08 (0.80, 1.44) | 1.00 (0.74, 1.34) | 1.19 (0.89, 1.60) | 1.06 (0.78, 1.45) | 0.56 |
| GLA | 1.0 (Reference) | 1.09 (0.81, 1.47) | 1.12 (0.83, 1.51) | 1.15 (0.85, 1.55) | 1.03 (0.76, 1.41) | 0.93 |
| DGLA | 1.0 (Reference) | 0.96 (0.71, 1.29) | 1.03 (0.77, 1.38) | 1.02 (0.76, 1.38) | 0.87 (0.63, 1.18) | 0.45 |
| Ischemic stroke (362 cases) | ||||||
| LA | 1.0 (Reference) | 1.00 (0.71, 1.40) | 0.90 (0.64, 1.27) | 0.88 (0.62, 1.26) | 0.88 (0.61, 1.27) | 0.38 |
| AA | 1.0 (Reference) | 1.07 (0.77, 1.49) | 1.05 (0.75, 1.47) | 1.08 (0.77, 1.51) | 1.17 (0.83, 1.66) | 0.39 |
| GLA | 1.0 (Reference) | 1.08 (0.76, 1.53) | 1.17 (0.83, 1.66) | 1.20 (0.85, 1.69) | 1.09 (0.76, 1.55) | 0.67 |
| DGLA | 1.0 (Reference) | 1.01 (0.70, 1.45) | 1.28 (0.91, 1.81) | 1.29 (0.91, 1.82) | 1.04 (0.72, 1.50) | 0.63 |
| Hemorrhagic stroke (65 cases) | ||||||
| LA | 1.0 (Reference) | 0.72 (0.30, 1.74) | 0.98 (0.44, 2.21) | 0.91 (0.39, 2.10) | 1.10 (0.47, 2.57) | 0.65 |
| AA | 1.0 (Reference) | 0.72 (0.34, 1.53) | 0.62 (0.28, 1.37) | 1.39 (0.71, 2.74) | 0.33 (0.12, 0.90) | 0.22 |
| GLA | 1.0 (Reference) | 1.43 (0.69, 2.98) | 1.16 (0.53, 2.54) | 1.04 (0.46, 2.33) | 0.95 (0.40, 2.24) | 0.60 |
| DGLA | 1.0 (Reference) | 0.73 (0.36, 1.45) | 0.46 (0.21, 1.03) | 0.55 (0.25, 1.22) | 0.62 (0.29, 1.35) | 0.17 |
CHD, coronary heart disease, LA, linoleic acid, AA, arachidonic acid, GLA, γ-linolenic acid, DGLA, di-homo-γ-linolenic acid.
See Table 1 for median fatty acid levels in each quintile. Adjusted for age (years), gender (male or female), race (white or non white), enrollment site (4 sites), education (<high school, high school, some college, or college graduate), smoking status (never, former, or current), prevalent diabetes (yes or no), atrial fibrillation (yes or no), and hypertension (yes or no), leisure-time physical activity (mcal/wk), body mass index (kg/m2), waist circumference (cm), alcohol use (6 categories), and plasma phospholipid long-chain n-3 PUFA (sum of EPA+DPA+DHA, % of total fatty acids).
Linear trend was tested by assigning to participants the median value in each quartile and assessing this as a continuous variable. Findings were similar when fatty acid concentrations were evaluated in their natural units as continuous exposures.
Including 427 CHD deaths, 154 stroke deaths, 37 other atherosclerotic deaths (e.g., due to abdominal aortic aneurysm, mesenteric ischemia/infarctions, or peripheral vascular disease), and 60 other cardiovascular deaths (e.g., due to aortic stenosis, nonischemic cardiomyopathy, or venous thromboembolism).
Subsets of CHD mortality, with adjudication as to whether the underlying event was arrhythmic or nonarrhythmic. Non-arrhythmic CHD mortality included Congestive heart failure death (n=84) and other non-arrhythmic CHD death (cardiac procedure, multiple CHD causes of death, and unknown mechanism of cardiac death, n=118).
Includes 418 nonfatal myocardial infarctions and 302 CHD deaths. Analyses of incident CHD deaths included an additional 125 deaths that occurred with additional follow-up after an incident nonfatal myocardial infarction.
Includes 362 ischemic strokes, 65 hemorrhagic strokes, and 36 strokes for which clinical information was insufficient for subtype classification.