Lability of serum low-density lipoprotein cholesterol levels during screening in subgroup of Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) cohort.
In the enrollment phase of the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), a number of heart disease-free potential subjects did not qualify to participate in the study because their low-density lipoprotein cholesterol (LDL-C) levels fluctuated. This report looks at the incidence of lability of LDL-C levels and premature coronary heart disease (CHD) in the nuclear family based on data collected on a group excluded primarily based on lipid levels during the enrollment phase at the TexCAPS site. Lipid inclusion criteria were total cholesterol (TC), 180 mg/dL to 264 mg/dL; low-density lipoprotein cholesterol (LDL-C), 130 mg/dL to 190 mg/dL; high-density lipoprotein cholesterol (HDL-C), less than or equal to 45 mg/dL for men and less than or equal to 47 mg/dL for women; and triglyceride (TG) concentrations, less than or equal to 400 mg/dL. After participants had been on the American Heart Association (AHA) step 1 diet for 8 to 10 weeks, lipid parameters were again tested in a total of 4257 individuals. Both lipid screening measurements at 8 and 10 weeks were required to be within 15% of each other for inclusion in subsequent study. A total of 2868 individuals met the study criteria and were randomly assigned to groups; 1389 failed to qualify for a variety of reasons. Of these, 1070 (25.1% of those who initially qualified based on lipid levels) were excluded because of unacceptable lipid levels on the evaluations repeated at 8 and 10 weeks. This excluded subpopulation (n = 1070) was stratified into three groups based on changes of LDL-C between 8 and 10 weeks on the AHA step 1 diet. One group had a less than 15% fluctuation in LDL-C (LN group, n = 637, 15.0% of cohort, n = 4257). Of those with LDL-C variability, 177 had a greater than 15% increase in LDL-C (LI group, n = 177, 4.2% of cohort); and 256 had a greater than 15% decrease in LDL-C (LD, n = 256, 6.0% of cohort). At week 8, TC and LDL-C levels were lower and the HDL-C level was higher in the LN group compared with both groups having labile lipid levels (LI and LD groups). Changes by gender showed similar trends; however, HDL-C was 5 mg/dL lower at 8 weeks in both groups of women with labile LDL-C levels (groups LI and LD) when compared with the women in the LN group (P < .01). The frequency of TG concentrations greater than 150 mg/dL was greater in men having labile LDL-C level when compared with the control group. The trend was similar for women. In assessing the incidence of CHD in the nuclear family, parents of probands with labile LDL-C levels (LI and LD groups) had a higher frequency (P = .0044) of premature CHD than parents of probands with stable LDL-C (LN). The following conclusions can be drawn: (1) within the general population, there is a substantial number (10%, 433 of 4257) of individuals with labile LDL-C levels; (2) labile LDL-C levels in the probands were found to be associated with an increased familial frequency of premature CHD in their parents. Definition of the molecular basis for this lability of LDL-C could reveal new opportunities to regulate plasma cholesterol levels and thus have an impact on CHD-associated morbidity and mortality in a substantial portion of the general population.
Department of Internal Medicine, University of North Texas Health Science Center, Forth Worth, Texas College of Osteopathic Medicine, 76107-2644, USA.
Michael B
MB
Clearfield
Stephen E
SE
Weis
John M
JM
Willis
Keith Allen
KA
Vasenius
Walter J
WJ
McConathy
D000368:Aged; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D011322:Primary Prevention; D016032:Randomized Controlled Trials as Topic; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol