Premature cardiovascular disease is common in relatives of patients with premature peripheral atherosclerosis.

BACKGROUND: Numerous clinical conditions have been proposed to explain the premature onset of symptomatic peripheral vascular disease (PVD) in young adults, but the role of genetic factors has not been defined. This study was performed to determine the prevalence of cardiovascular disease among family members of patients with premature PVD. METHODS: The prevalence of early cardiovascular events occurring in first-degree relatives of 90 subjects with premature PVD (onset < or =49 years) was determined. The prevalence of occult atherosclerosis was determined by duplex ultrasonography in a cohort of 20 asymptomatic siblings. Reference groups included first-degree relatives of 80 subjects with premature coronary artery disease (CAD) and first-degree relatives of 48 healthy subjects. RESULTS: Cardiovascular events occurred at age 55 years or younger in 28% of the parents of PVD subjects, in 23% of parents of CAD subjects, and in 7% of the parents of healthy controls (P<.001). Cardiovascular events occurred in 24% of siblings of PVD subjects, in 14% of siblings of CAD subjects, and in 7% of siblings of healthy controls (P<.001). Duplex ultrasonography detected early plaques in the lower extremity circulation of 10 (50%) of the asymptomatic siblings of PVD subjects. CONCLUSIONS: Early, symptomatic cardiovascular disease is more common in first-degree relatives of individuals with premature PVD than in relatives of healthy individuals or of probands with premature CAD. Occult vascular disease in the lower extremity is prevalent among asymptomatic siblings of probands with premature PVD. These observations indicate that susceptibility to premature PVD has a familial basis.

The -514 polymorphism in the hepatic lipase gene (LIPC) does not influence androgen-mediated stimulation of hepatic lipase activity.

The -514T allele of hepatic lipase is associated with increased high density lipoprotein-cholesterol levels in men, but not in women. This observation suggests that the -514C to T polymorphism may diminish the response of hepatic lipase to androgens. To test this hypothesis, five -514T and five -514C homozygous men were treated with the anabolic steroid stanozolol for 6 days. The mean increase in hepatic lipase activity was similar in the two groups (45+/-10 vs. 51+/-10 mmol x hr(-1) x l(-1), P = 0.5). To evaluate the association between the -514 polymorphism and hepatic lipase activity at different physiological androgen concentrations, hepatic lipase genotypes and activities were measured in 44 men and 40 premenopausal women. The effect of the -514T allele on hepatic lipase activity was significant and quantitatively similar in both sexes. These data indicate that the -514 polymorphism does not influence the response of hepatic lipase activity to androgens, and that the effects of this polymorphism on hepatic lipase activity are independent of androgen action.

Genetic analysis of a polymorphism in the human apolipoprotein A-I gene promoter: effect on plasma HDL-cholesterol levels.

Previous studies have indicated that a G to A substitution at position -76 in the gene encoding apolipoprotein A-I (apoA-I) confers increased plasma high density lipoprotein cholesterol (HDL-C). Increased HDL-C may be a direct consequence of the A allele, or may reflect the action of a locus in linkage disequilibrium with the A allele. To elucidate this question, we examined the effect of this polymorphism in a large sample (n = 409) of unrelated Caucasians and their nuclear families (n = 22). To eliminate the confounding effects of hypertriglyceridemia, individuals with triglyceride levels greater than 150 mg/dl were excluded from the study. ApoA-I genotype was determined by polymerase chain reaction (PCR) amplification of genomic DNA and restriction digestion with Msp I. Individuals were grouped by genotype (GG, GA or AA) and mean adjusted HDL levels of the three groups were compared by one-way analysis of variance. Our analysis indicates that HDL-C levels do not vary by genotype, and no gene dosage effect is apparent in men or in women. Analysis of 22 informative Caucasian nuclear families showed no significant difference between individuals with the A allele and their GG siblings. These data suggest that polymorphism at -76 in the apoA-I gene does not directly affect HDL levels. Therefore, the increased HDL-C levels reported in other populations must reflect linkage disequilibrium between the A allele and a putative HDL-raising allele. As we find no evidence for association between the A allele and high HDL levels, this putative allele must occur at a low frequency in the population sampled in this study.

Step ergometry: is it task-specific training?

Maximal exercise responses were measured before and after 10 weeks of training in two groups of men, one trained on a treadmill (n = 12) and the other on a step ergometer (n = 9); the groups were pre- and post-tested on both machines to examine the specificity of the training modes. Training for both groups consisted of 3 days week-1, 30 min day-1, progressing to 50 min day-1, at an intensity of 75%-80% heart rate maximum reserve. Pre-training maximal oxygen uptake (VO2max) was significantly higher on the treadmill for both groups (X = 8.5%). VO2max increased 6.9% on the treadmill (P less than 0.05) and 6.9% (P greater than 0.05) on the step ergometer after treadmill training. The small increases may be attributed to the specificity of the testing protocols used to elicit VO2max. Significant (P less than 0.01) increases in VO2max were found for both modalities after step-ergometry training (treadmill = 11.8%; step ergometer = 23.2%). These increases resulted in equal post-test VO2max values (4.05 l min-1; 51 ml kg-1 min-1) on the step ergometer and treadmill. The significant increases in VO2max found for both modalities after step-ergometry training shows that (1) step ergometry is an effective training modality, and (2) its effects can be measured on the treadmill and therefore it is not task-specific training.

Stair climbing: an alternative exercise modality for firefighters.

The purpose of this investigation was to determine the maximal cardiorespiratory responses of firefighters to stair-climbing work and to compare these responses to maximal treadmill exercise. Thirty-eight firefighters volunteered to participate in the study. Maximal CR including oxygen consumption (VO2), ventilatory equivalent for oxygen (VE/VO2), minute ventilation (VE) and heart rate (HR) were measured during both stair climbing and graded treadmill exercise. The results showed that VO2max and HRmax were significantly lower, 7% and 2% respectively, and the VE/VO2 was significantly higher (6.7%) during the stair-climbing exercise. Maximal VE was not different between the two modes of exercise. The results suggest that since VO2max and HRmax were lower during stair climbing, the metabolic cost of firefighting tasks as related to VO2max on a treadmill may not be accurately reflected. Since stair climbing is a task-specific activity for firefighters, it is recommended that testing of firefighters be performed on a stair-climbing device, and that the difference in VO2max between treadmill and stair-climbing exercise be considered when recommending a desired fitness level for firefighters.