Background: It remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is prospectively associated with incident peripheral arterial disease (PAD).Methods: We included 12,320 Atherosclerosis Risk in Communities Study participants (aged 54.3 ± 5.7 years) free of a history of PAD at baseline (visit 1: 1987–1989). The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and measured at 5 visits between 1987 and 2013. Incident PAD was defined as the first hospitalization with PAD diagnosis or a new onset of measured ABI < 0.90 during follow-up visits. We quantified the association of both baseline and trajectories of TyG index with incident PAD using Cox regression and logistic regression analysis, respectively.Results: Over a median follow-up of 23 years, 1300 participants developed PAD. After adjustment for traditional PAD risk factors, each 1-SD (0.58) increase in TyG index was associated with an 11.9% higher risk of incident PAD [hazard ratio, 1.119 (95% CI, 1.049–1.195)]. Results were similar when individuals were categorized by TyG index quartiles [hazard ratio, 1.239 (95% CI, 1.028–1.492); comparing extreme quartiles]. Four distinct trajectories of stable TyG indexes at various levels along the follow-up duration were identified [low (22.2%), moderate (43.2%), high (27.5%), and very high (7.1%) trajectory groups]. Compared with those with a TyG index trajectory at a low level, those participants with TyG index trajectories at high and very high levels had an even greater risk of future incident PAD [odds ratio (95%CI): 1.404 (1.132–1.740) and 1.742 (1.294–2.344), respectively] after multivariate adjustments for traditional PAD risk factors.Conclusions: Higher TyG index is independently associated with an increased risk of incident PAD. Long-term trajectories of TyG index help identify individuals at a higher risk of PAD who deserve specific preventive and therapeutic approaches.Trial registration: Clinical trial registration number: The ARIC trial was registered at clinicaltrials.gov as NCT00005131.

A series of clinical trials have confirmed the correlation between vascular calcification (VC) and cardiovascular events and mortality. However, current treatments have little effects on the regression of VC. Potent and illustrative mechanisms have been proven to exist in both bone metabolism and VC, indicating that these two processes share similarities in onset and progression. Multiple osteoblast-like cells and signaling pathways are involved in the process of VC. In this review, we summarized the roles of different osteoblast-like cells and we emphasized on how they communicated and interacted with each other using different signaling pathways. Further studies are needed to uncover the underlying mechanisms and to provide novel therapies for VC.

Background: Remnant cholesterol (RC) contributes to residual risk of atherosclerotic cardiovascular disease, but population-based evidence on the prospective relationship between RC and coronary artery calcium (CAC) progression is rare. Methods: We pooled data obtained from 6544 atherosclerotic cardiovascular disease–free individuals from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=2635) and MESA (Multi-Ethnic Study of Atherosclerosis; n=3909), with a mean±SD age of 47.2±19.8 years; 3019 (46.1%) were men who completed computed tomography of CAC at baseline. RC was measured as total cholesterol minus HDL (high-density lipoprotein) cholesterol minus calculated LDL (low-density lipoprotein) cholesterol (LDL-C) estimated by using the Martin/Hopkins equation. Adjusted Cox models were used to assess the relationships between RC levels and CAC progression. We also performed discordance analyses examining the risk of CAC progression in RC versus LDL-C discordant/concordant groups using median cut points and clinically relevant LDL-C targets. Results: During a median follow-up of 8.6 years, 2778 (42.5%) participants had CAC progression. After multivariable adjustment for demographics and cardiovascular risk factors, a 1-mg/dL increase in RC levels was associated with a 1.3% higher risk of CAC progression (hazard ratio, 1.013 [95% CI, 1.008–1.017]). Results were similar when we categorized individuals by RC quartiles. Furthermore, the discordant high RC/low LDL-C group had a significantly higher risk of CAC progression than the concordant low RC/LDL-C group regarding their medians (hazard ratio, 1.195 [95% CI, 1.063–1.343]) or when setting the clinical LDL-C cut points at 100 and 130 but not 70 mg/dL. The association remained robust across a series of sensitivity analyses. Conclusions: Elevated RC levels were associated with an increased risk of CAC progression independent of traditional cardiovascular risk factors, even in individuals with optimal LDL-C levels. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT00005130 (CARDIA) and NCT00005487 (MESA).

Objective: To investigate whether low-carbohydrate diets (LCDs) were associated with coronary artery calcium (CAC) progression. Approach and Results: We included the participants who completed computed tomography assessment of baseline CAC in 2000 to 2001 (year 15) and follow-up (year 20 or 25) and food frequency questionnaire (years 0, 7, and 20) in the CARDIA study (Coronary Artery Risk Development in Young Adults). CAC progression was defined as CAC >0 at follow-up among participants with baseline CAC of 0 and an annualized change of 10 or percent change of ≥10% for those with 0<baseline CAC<100 or baseline CAC≥100, respectively. Among 2226 included participants (age, 40.4±3.5 years; 45.4% men), the carbohydrate intake accounted for 47.8±6.5% of total energy, and 204 (9.2%) had CAC at baseline (year 15). Over a mean follow-up of 8.3 years, 591 (26.5%) participants had CAC progression. After adjustment for traditional cardiovascular risk factors and other dietary factors, carbohydrate intake as a percentage of total energy was inversely associated with the risk of CAC progression (hazard ratio, 0.731 [95% CI, 0.552–0.968]; P =0.029). Furthermore, the animal-based but not plant-based LCD score was significantly associated with a higher risk of CAC progression (animal-based LCD score: hazard ratio, 1.456 [95% CI, 1.015–2.089]; P =0.041; plant-based LCD score: hazard ratio, 1.016 [95% CI, 0.821–1.257]; P =0.884; both comparing extreme groups). Conclusions: LCDs starting at a young age are associated with an increased risk of subsequent CAC progression, particularly when animal protein or fat are chosen to replace carbohydrates. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00005130.