3.1 Baseline Characteristics
The baseline characteristics of the study population stratified according to sex and race are shown in . Overall, mean age was 45 ± 9 years and 44% were men; 30% were white, 17% hispanic, and 53% black. Compared with men, women were more likely to have a family history of myocardial infarction, and less likely to smoke, or take aspirin. Women had higher high-sensitivity C-reactive protein (hsCRP) and high-density lipoprotein (HDL) cholesterol and lower LDL cholesterol and triglycerides. Compared with whites and hispanic subjects, black subjects were more likely to have hypertension and had higher median CRP. Mean and median Lp-PLA2 activity was 146 ± 40 and 144 nmol/min/mL, respectively. Mean and median Lp-PLA2 mass was 191 ± 60 and 187 ng/mL, respectively. There was a strong correlation between Lp-PLA2 mass and activity (Spearman’s rho=0.69, p<0.001, ).
Baseline characteristics of the study population stratified by race and sex.
Association between Lp-PLA2 activity and Lp-PLA2 mass in the study population.
3.2 Associations between clinical variables and Lp-PLA2 activity
Lp-PLA2 activity was positively associated with total cholesterol (rho=0.30), LDL cholesterol (rho=0.42) and triglycerides (rho=0.19), and negatively associated with HDL cholesterol (rho= −0.37) and hs-CRP (rho= −0.15) (p<0.001 for each). Lp-PLA2 activity was higher in current smokers vs. non- smokers (150 ± 41 vs. 145 ± 39, p<0.001), and lower in hypertensive vs. normotensive subjects (142 ± 40 vs. 148 ± 39, p<0.001), in subjects taking statins vs. non-users (141 ± 38 vs. 147 ± 39, p=0.03), and in female users of oral estrogen vs. non-users (126 ± 35 vs. 136 ± 34, p<0.001). Lp-PLA2 levels were not associated with the presence of diabetes or with family history of coronary artery disease.
The association of Lp-PLA2 activity with several continuous parameters, stratified by race and sex, is shown in . Except among black men, Lp-PLA2 activity was not associated with age, body mass index, or creatinine clearance. Lp-PLA2 activity had a modest negative association with hsCRP levels in women but not in men. Data were qualitatively similar for Lp-PLA2 mass (data not shown).
Association (Spearman rank correlation and p-value) of Lp-PLA2 activity with different continuous parameters across various sex/race strata.
3.3 Association of Lp-PLA2 activity and mass with race and sex
Lp-PLA2 activity was significantly lower in women compared with men (134 ± 35 vs. 161 ± 40; p=0.001). Lp-PLA2 activity was lowest in black (136 ± 38), intermediate in hispanic (151 ± 36), and highest in white subjects (161 ± 39) (p=0.0001) (). Similar sex and race associations were observed for Lp-PLA2 mass ().
Figure 2 Lp-PLA2 activity (Fig. 2a) and mass (Fig. 2b) in 3,332 subjects classified according to race and sex. The upper, middle, and lower line of the shaded box correspond to the 75th percentile, median, and 25th percentile value, respectively. The upper line (more ...)
Based on univariable analyses, candidate covariates tested in the multivariable linear regression model for Lp-PLA-2 activity included age, body mass index (BMI), smoking, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and hsCRP In the final model that included smoking, LDL and HDL cholesterol, and hsCRP, race and sex remained independently associated with Lp-PLA2 activity. Adjusted Lp-PLA2 activity was 19 nmol/min/mL higher in men vs. women (p<0.001); compared with black subjects, adjusted Lp-PLA2 activity was 11 nmol/min/mL higher in hispanic and 20 nmol/min/mL higher in white subjects (both p<0.001).
Similarly, candidate covariates tested in the multivariable linear regression model for Lp-PLA-2 mass included age, BMI, hypertension, smoking, total cholesterol, LDL-cholesterol, HDL cholesterol, triglycerides and hsCRP. In the final model that included smoking, BMI, total and HDL cholesterol, race and sex remained independently associated with Lp-PLA2 mass. Adjusted Lp-PLA2 mass was 19 ng/mL higher in men vs. women (p<0.001); compared with black subjects, adjusted Lp-PLA2 mass was 9 ng/mL higher in hispanic and 24 ng/mL higher in white subjects (both p<0.001).
To determine the contribution of race and sex in the prediction of Lp-PLA2 levels, several multivariable linear regression models were created with Lp-PLA2 activity as the endpoint: (1) a baseline model that included LDL cholesterol, HDL cholesterol, C-reactive protein, and current smoking; (2) the baseline model with sex added; (3) the baseline model with race added, and (4) the baseline model with sex and race added (). Addition of race and sex improved the prediction of Lp-PLA2 levels as shown by the increase in adjusted R2 from 0.31 in model 1 to 0.41 in model 4.
Figure 3 Adjusted R2 in four multivariable linear regression models with Lp-PLA2 activity as the endpoint: (1) baseline model that includes LDL cholesterol, LDL cholesterol, high sensitivity C-reactive protein, and current smoking; (2) baseline model with sex (more ...)