Cardiometabolic risk factors in siblings from a statewide screening program

Abstract

Background: The Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project is a state-wide risk factor screening program that operated in West Virginia for 19 years and screened more than 100,000 5th graders for obesity, hypertension, and dyslipidemia.

Objectives: We investigated siblings in the CARDIAC Project to assess whether cardiometabolic risk factors (CMRFs) correlate in siblings.

Methods: We identified 12,053 children from 5752 families with lipid panel, blood pressure, and anthropometric data. A linkage application (LinkPlus from the U.S. Centers for Disease Control and Prevention) matched siblings based on parent names, addresses, telephone numbers, and school to generate a linkage probability curve. Graphical and statistical analyses demonstrate the relationships between CMRFs in siblings.

Results: Siblings showed moderate intraclass correlation coefficient of 0.375 for low-density lipoprotein cholesterol (LDL-C), 0.34 for high-density lipoprotein cholesterol (HDL-C), and 0.22 for triglyceride levels. The body mass index (BMI) intraclass correlation coefficient (0.383) is slightly better (2%) than LDL-C or HDL-C, but the standardized beta values from linear regression suggest a 3-fold impact of sibling LDL-C over the child's own BMI. The odds ratio of a second sibling having LDL-C < 110 mg/dL with a first sibling at that level is 3.444:1 (Confidence Limit 3.031-3.915, P < .05). The odds ratio of a sibling showing an LDL-C ≥ 160 mg/dL, given a first sibling with that degree of elevated LDL-C is 29.6:1 (95% Confidence Limit: 15.54-56.36). The individual LDL-C level correlated more strongly with sibling LDL-C than with the individual's own BMI. Seventy-eight children with LDL-C > 160 mg/dL and negative family history would have been missed, which represents more than half of those with LDL-C > 160 mg/dL (78 vs 67 or 54%).

Conclusions: Sibling HDL-C levels, LDL-C levels, and BMIs correlate within a family. Triglyceride and blood pressure levels are less well correlated. The identified CMRF relationships strengthen the main findings of the overall CARDIAC Project: an elevated BMI is not predictive of elevated LDL-C and family history of coronary artery disease poorly predicts cholesterol abnormality at screening. Family history does not adequately identify children who should be screened for cholesterol abnormality. Elevated LDL-C (>160 mg/dL) in a child strongly suggests that additional siblings and parents be screened if universal screening is not practiced.

Keywords: Body mass index; Cardiometabolic risk factors; Cholesterol; Cholesterol screening; Familial hypercholesterolemia; Low-density lipoprotein cholesterol; Siblings.

Figure 1

Percent sensitivity by the match probability score (X-axis, ranging from 62 to 14) generated by LinkPlus. Each sensitivity data point represents a sample of 50 matches and the curve depicts high sensitivity to a probability score of 25.3. The probability score is a relative scale determined by LinkPlus.

Figure 2

Heat maps of sib 1 and sib 2 pairings. Findings for the first sibling screened are displayed on the x-axis and those for the second sibling on the y-axis. (A) Low-density lipoprotein (mg/dL), (B) BMI z score (SD), (C) triglyceride levels (mg/dL), (D) high-density lipoprotein (mg/dL), and (E) total cholesterol (mg/dL).