Background South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine- rather than cystatin C-based estimated glomerular filtration rate (eGFRcys) may underestimate the cardiovascular disease risk associated with chronic kidney disease. Methods and Results Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atherosclerotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine-based estimated glomerular filtration rate categories (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m²) with risks of all-cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio [HR], 2.38 [95% CI, 1.55-3.65]) and incident HF (sub-HR [sHR], 1.87 [95% CI, 1.09-3.22]) versus the eGFRcys ≥90 category; the creatinine-based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine-based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 [95% CI, 2.56-9.31]), incident HF (sHR, 4.96 [95% CI, 2.21-11.16]), and incident atherosclerotic cardiovascular disease (sHR, 2.29 [95% CI, 1.14-4.61]) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 [95% CI, 1.45-3.51]). Conclusions Among South Asian individuals, cystatin C identified a high-risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate-based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease.

Background

Current guidelines recommend that patients with peripheral arterial disease (PAD) cease smoking and be treated with aspirin, statin medications, and angiotensin-converting enzyme (ACE) inhibitors. The combined effects of multiple guideline-recommended therapies in patients with symptomatic PAD have not been well characterized.

Methods and results

We analyzed a comprehensive database of all patients with claudication or critical limb ischemia (CLI) who underwent diagnostic or interventional lower-extremity angiography between June 1, 2006 and May 1, 2013 at a multidisciplinary vascular center. Baseline demographics, clinical data, and long-term outcomes were obtained. Inverse probability of treatment propensity weighting was used to determine the 3-year risk of major adverse cardiovascular or cerebrovascular events (MACE; myocardial infarction, stroke, or death) and major adverse limb events (MALE; major amputation, thrombolysis, or surgical bypass). Among 739 patients with PAD, 325 (44%) had claudication and 414 (56%) had CLI. Guideline-recommended therapies at baseline included use of aspirin in 651 (88%), statin medications in 496 (67%), ACE inhibitors in 445 (60%), and smoking abstention in 528 (71%) patients. A total of 237 (32%) patients met all four guideline-recommended therapies. After adjustment for baseline covariates, patients adhering to all four guideline-recommended therapies had decreased MACE (hazard ratio [HR], 0.64; 95% CI, 0.45 to 0.89; P=0.009), MALE (HR, 0.55; 95% CI, 0.37 to 0.83; P=0.005), and mortality (HR, 0.56; 95% CI, 0.38 to 0.82; P=0.003), compared to patients receiving less than four of the recommended therapies.

Conclusions

In patients with claudication or CLI, combination treatment with four guideline-recommended therapies is associated with significant reductions in MACE, MALE, and mortality.

Objectives

Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD).

Background

The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear.

Methods

This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention.

Results

The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20%) and clopidogrel HoTPR in 76 (49%) patients. There was a trend toward more primary composite outcome events with PRU ≥ 235 (52% freedom-from-event rate vs. 70% for PRU < 235; P = 0.09). TVR was higher in those with PRU ≥ 235 (20 vs. 6%, unadjusted P = 0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P = 0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P = 0.002).

Conclusion

Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.