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.

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.

Background It remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of IR, was prospectively associated with incident PAD. Methods We included 12573 ARIC (Atherosclerosis Risk in Communities Study) participants free of PAD at baseline (1987–1989). The TyG index was determined using ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and measured during 5 visits between 1987 and 2013. Incident PAD was defined as the first hospitalization with PAD diagnosis. 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, there were 1331 cases of incident PAD. After adjustment for traditional PAD risk factors, each 1-SD (0.58) increase in TyG index was associated with an 18.9% higher risk of incident PAD (hazard ratio, 1.189 [95% CI, 1.106–1.278]). Results were similar when individuals were categorized by TyG index quartiles (hazard ratio, 1.363 [95% CI, 1.125–1.652]; comparing extreme quartiles). Four distinct trajectories of TyG index were identified (low-increasing [43.0%], moderate-stable [22.3%], moderate-decreasing [27.6%], and high-decreasing [7.1%]). Trajectories of elevated TyG index levels had greater incident PAD after multivariable adjustment for potential cardiovascular risks. Compared with moderate-stable group (reference), high-decreasing group was associated with the highest risk of future incident PAD (odds ratio, 2.314 [95%CI, 1.687–3.175]). Conclusion Higher TyG index is independently associated with incident PAD. Long-term trajectories of TyG index help identify individuals at a higher risk of future PAD who deserve appropriate follow-up to detect asymptomatic disease.