Clinical outcomes of bypass-first versus endovascular-first strategy in patients with chronic limb-threatening ischemia due to infrageniculate arterial disease

Background

Chronic limb-threatening ischemia (CLTI), defined as ischemic rest pain or tissue loss secondary to arterial insufficiency, is caused by multilevel arterial disease with frequent, severe infrageniculate disease. The rise in CLTI is in part the result of increasing worldwide prevalence of diabetes, renal insufficiency, and advanced aging of the population. The aim of this study was to compare a bypass-first with an endovascular-first revascularization strategy in patients with CLTI due to infrageniculate arterial disease.

Polymorphism in the promoter region of the apolipoprotein AI gene associated with differences in apolipoprotein AI levels: The European Atherosclerosis Research Study

The effect associated with the substitution of adenine (A) for guanidine (G) in the promoter region of the apolipoprotein AI gene (?75 bp) with plasma apo AI and high-density lipoprotein (HDL) levels was investigated in the European Atherosclerosis Research Study (EARS). This is a study of healthy offspring (cases) of fathers who had suffered premature myocardial infarction (MI) before age 55 years (n = 565) and age- and sex-matched controls (n = 1,078) from 12 European countries, divided into 5 regions based on geography and language. The frequency of the polymorphism was not significantly different among the regions and the relative frequency of the rare A allele was similar in cases and controls (0.159 vs. 0.142) combining data from all regions. Individuals with one or more A allele had significantly higher plasma apo AI levels (P < 0.05) than individuals homozygous for the G allele. This effect was consistent in all regions. The data were analyzed separately in males and females. In females, those with one or more A allele had significantly higher apo AI levels (P = 0.05) than individuals homozygous for the G allele, and this raising effect of the A allele was greater in cases than controls for both apo AI (5.23% vs. 1.56%) and HDL (4.48% vs. 1.89%). In males, the A allele was associated with higher levels of apo AI and HDL, but the effect was much smaller and the differences did not reach statistical significance. In the females, where the effect of the A allele was strongest, the effect on apo AI associated with genotype was evident in non-smokers, and individuals with one or two A alleles had 3.6% higher apo AI and 3.14% higher HDL levels than individuals homozygous for the G allele. However, in the female smokers the raising effect of the A allele was greatly reduced (0.56%). Thus genetic variation in the promoter region of the apo AI gene is associated with differences in apo AI and HDL levels in healthy individuals throughout Europe, but the effect is modulated by gender, environmental factors such as smoking, and a family history of MI.     

Interaction of the cholesteryl ester transfer protein I405V polymorphism with alcohol consumption in smoking and non-smoking healthy men, and the effect on plasma HDL cholesterol and apoAI concentration

Three hundred and sixteen healthy Icelandic men and women were examined for the effect of the cholesteryl ester transfer protein (CETP) I405V polymorphism on plasma triglycerides, HDL cholesterol (HDLC) and apoAI concentration. Genotyping was performed using an allele specific oligomelting assay and the frequency of the V allele was 0.31 (95 CI for men 0.23–0.33 and for women 0.29–0.39). In women no significant difference was associated with the V405 genotype for any plasma lipid trait. However, men who were homozygous for the V405 allele had 9% higher apoAI and 14% higher HDLC levels (p < 0.05) than those homozygous for the common 1405 allele. The genotype effect was seen only in the non-smokers (p = 0.07 and <0.05, respectively), and in those consuming alcohol (p < 0.05 for both). Analysis of interaction between the environmental, life-style factors and genotype in men for the traits of HDLC and apoAI showed statistically significant interaction of the genotype only with alcohol consumption. The non-smoking men who reported alcohol consumption and who were homozygous for the CETP V405 allele had 16% higher plasma apoAI concentration than those who carried the 1405 allele, and up to 20% higher apoAI level than smokers. On the basis of prospective studies carried out on the Icelandic population, non-smoking, alcohol-consuming men who are homozygous for the V405 allele could have from 32% to 40% lower risk of having a heart attack.