Lipoprotein Particle Profiles, Standard Lipids, and Peripheral Artery Disease Incidence

Abstract

-Despite strong and consistent prospective associations of elevated low-density lipoprotein-cholesterol (LDL-C) concentration with incident coronary and cerebrovascular disease (CCVD), data for incident peripheral artery disease (PAD) are less robust. Atherogenic dyslipidemia characterized by increased small LDL particle concentration (LDL-P), rather than total LDL cholesterol content, along with elevated triglyceride-rich lipoproteins and low high-density lipoprotein-cholesterol (HDL-C) may be the primary lipid driver of PAD risk. -The study population was a prospective cohort study of 27,888 women ≥45 years old free of cardiovascular disease at baseline and followed for a median of 15.1 years. We tested whether standard lipid concentrations as well as nuclear magnetic resonance (NMR) spectroscopy-derived lipoprotein measures were associated with incident symptomatic PAD (n=110) defined as claudication and/or revascularization. -In age-adjusted analyses, while LDL-C was not associated with incident PAD, we found significant associations for increased total and small LDL-P concentrations, triglycerides, and concentrations of very low-density lipoprotein particle subclasses (VLDL-P), increased total cholesterol (TC):HDL-C, low HDL-C, and low HDL particle concentration (HDL-P) (all for extreme tertile comparisons<0.05). Findings persisted in multivariable-adjusted models comparing extreme tertiles for elevated total LDL-P (HR 2.03; 95% CI, 1.14 to 3.59), small LDL-P [HR 2.17 (1.10 to 4.27)], very large VLDL-P (HR 1.68 (1.06 to 2.66)], medium VLDL-P (HR 1.98 (1.15 to 3.41)], and TC:HDL-C [HR, 3.11 (1.67 to 5.81)]. HDL was inversely associated with risk; HR for extreme tertiles of HDL-C and HDL-P were 0.30 (P-trend <0.0001) and 0.29 (P-trend <0.0001), respectively. These components of atherogenic dyslipidemia, including small LDL-P, medium and very large VLDL-P, TC:HDL-C, HDL-C, and HDL-P, were more strongly associated with incident PAD than incident CCVD. Finally, the addition of LDL-P and HDL-P to TC:HDL-C measures identified women at heightened PAD risk. -In this prospective study, NMR-derived measures of LDL particle concentration, but not LDL-C, were associated with incident PAD. Other features of atherogenic dyslipidemia, including elevations in TC:HDL-C, elevations in triglyceride-rich lipoproteins, and low standard and NMR-derived measures of HDL, were significant risk determinants. These data help clarify prior inconsistencies and may elucidate a unique lipoprotein signature for PAD compared to CCVD. -URL: http://clinicaltrials.gov Unique Identifier: NCT00000479.

Hypertriglyceridemia is associated with an increased risk of peripheral arterial revascularization in high‐risk statin‐treated patients: A large administrative retrospective analysis

“…This large administrative retrospective study, which analyzed claims data from more than 45 000 statin‐treated patients in the Optum Research Database, showed that both elevated TG (≥150 mg/dL) and high TG (200‐499 mg/dL) were significant predictors of peripheral arterial revascularization (37% and 49% increased risk, respectively) in patients with high CV risk. These data support previous studies reporting an association between an atherogenic lipoprotein phenotype (elevated TG, reduced HDL‐C, and decreased LDL size) and increased risk of PAD …”

“…These data support previous studies reporting an association between an atherogenic lipoprotein phenotype (elevated TG, reduced HDL-C, and decreased LDL size) and increased risk of PAD. [14][15][16] We previously showed that these elevated-and high-TG patient populations had worse CV outcomes and higher health care resource use and direct costs than patients with TG <150 and HDL-C > 40 mg/dL. 11,12 In patients with elevated TG and high TG, respectively, the overall risk of a major CV event was 26% and 35%…”

Gene-expression profiles of abdominal perivascular adipose tissue distinguish aortic occlusive from stenotic atherosclerotic lesions and denote different pathogenetic pathways

“…Conversely, the association of St-patients with the "fatty acid metabolism" pathway in both the omental-visceral and subcutaneous AT and the "low-density lipoprotein particle metabolic process" in the subcutaneous AT is intriguing, since both the visceral and subcutaneous AT are energy storage tissues and lipid catabolic regulation can be triggered to reduce the effects of atherogenic stimuli, as demonstrated in in vivo animal models 24 . Moreover, PAD has been suggested to have a unique lipoprotein signature compared to coronary and cerebrovascular diseases, mainly characterized by increased low-density lipoprotein particles rather than LDL cholesterol content 25 . As AT are also known to regulate serum lipids 26 , reducing LDL particles through upregulation of the LDL particle receptor in AT may represent a feedback mechanism to lessen circulating LDL particles in St-patients, similar to what happens with the use of lipid-lowering therapies 27 .…”

Residual cardiovascular risk among people with diabetes

“…In prospective studies in women, plasma TG and ApoB concentration were an excellent predictor of CVD, particularly in those with LDL‐C concentration less than the median population concentration. Similarly, plasma TG and TRL were a predictor of peripheral arterial disease risk . The predictive power of plasma TG for future CVD was reversed after adjustment of plasma TG for non‐HDL cholesterol (a surrogate measure of TRL and TRL remnant particles) and HDL .…”

“…Similarly, plasma TG and TRL were a predictor of peripheral arterial disease risk. 60 The predictive power of plasma TG for future CVD was reversed after adjustment of plasma TG for non-HDL cholesterol (a surrogate measure of TRL and TRL remnant particles) and HDL. 61 This suggests that TRL and their remnants may be atherogenic.…”