Renal artery stenosis predicts adverse cardiovascular and renal outcome in patients with peripheral artery disease.

BACKGROUND: Patients with symptomatic peripheral artery disease (PAD) are considered cardiovascular high-risk patients. Our aim was to investigate whether incidental renal artery stenosis (RAS) increases the risk for adverse cardiovascular and renal outcomes in these patients. MATERIALS AND METHODS: We prospectively enrolled 487 consecutive patients admitted for revascularization of symptomatic PAD and performed a renal overview angiogram categorizing RAS as absent (0-29%), moderate (30-59%) and severe (>or= 60%) respectively. Clinical follow-up was for median 15 months (IQR 12-22) for the occurrence of major adverse events [MAE: composite of death, myocardial infarction (MI), stroke, percutaneous coronary intervention, coronary bypass surgery, amputation and kidney failure]. Glomerular filtration rates (GFR) were obtained at 12 months to quantify the course of renal function. RESULTS: A severe RAS was found in 76 patients (15.6%). Overall MAE occurred in 121 patients (24.8%), the composite endpoint of MI, stroke, amputation and death occurred in 101 patients (20.7%). Patients with a severe RAS had a 1.87-fold increased adjusted risk for MAE (95% CI 1.12-3.12, P = 0.017), a 2.51-fold increased adjusted risk for occurrence of the composite endpoint of MI, stroke, amputation and death (95% CI 1.45-4.34, P = 0.001) and a 2.93-fold increased risk for death (95% CI 1.41-6.08, P = 0.004), compared to those of patients without RAS respectively. We observed a significant association between the decrease of GFR over the 12-month follow-up period and the severity of RAS by multivariable analysis (P = 0.044). CONCLUSION: Severe RAS in patients with symptomatic PAD is an independent predictor of major adverse cardiovascular events, adverse renal outcome and mortality.

Haem oxygenase-1 genotype and cardiovascular adverse events in patients with peripheral artery disease.

BACKGROUND: A functional GT dinucleotide length polymorphism in the haem oxygenase-1 (HO-1) gene promoter is thought to be involved in the pathogenesis of cardiovascular disease. Short (< 25) (GT)n repeats are suggested to facilitate enhanced HO-1 up-regulation in response to injury and confer potent anti-inflammatory and antioxidative effects. MATERIALS AND METHODS: We investigated the association between the HO-1 GT-polymorphism and cardiovascular outcome in 472 patients with advanced peripheral artery disease. Cardiovascular risk profile and DNA samples for determination of the HO-1 genotype (carrier vs. noncarrier of a short (GT)n repeat allele) were obtained at baseline, and patients were followed for median 21 months for the occurrence of coronary events (myocardial infarction, percutaneous coronary interventions and coronary artery bypass graft), cerebrovascular events (stroke or carotid revascularization) and all-cause mortality. RESULTS: Coronary events occurred in 48 patients (9%), cerebrovascular events in 40 patients (9%) and 59 patients (13%) died. In total, 173 major adverse cardiovascular events (MACE) occurred in 133 patients (28%). Carriers of the short (GT)n repeat allele had a 0.46-fold reduced adjusted hazard ratio for coronary events (P = 0.016) as compared to noncarriers. No significant difference was found for cerebrovascular events, mortality and overall MACE. CONCLUSION: Apparently, the HO-1 genotype exerts potentially protective effects against coronary adverse events in patients with peripheral artery disease. Homozygous and heterozygous carriers of < 25 (GT)n repeats had lower rates of myocardial infarction, percutaneous coronary interventions and coronary bypass operations compared to patients with longer (GT)n repeats.

Outcome of conservative therapy of patients with severe intermittent claudication.

BACKGROUND: Intermittent claudication due to peripheral artery disease (PAD) can be treated conservatively, or by revascularization. OBJECTIVES: To assess the short-term outcome of conservatively-treated claudicants, and determine predictors for clinical improvement. Design. A retrospective cohort study. METHODS: We evaluated Fontaine stage, walking distance and ankle brachial index (ABI) at baseline and after median 9 months (interquartile range (IQR) 6-24) in 181 patients with severe claudication. RESULTS: We found clinical improvement by at least one Fontaine stage in 38 patients (21%) with an increased walking distance from baseline median 100 m (IQR 50-150) to follow-up median 650 m (IQR 300 to unlimited; p<0.001), but without changes in ABI (median 0.57, IQR 0.48-0.73 vs. median 0.54, IQR 0.45-0.81; p=0.10). One hundred and thirty-eight patients (76%) remained clinically and hemodynamically stable. A worsening of the clinical stage but without amputation was recorded in five patients (3%). Female gender (hazard ratio (HR) 0.51, p=0.052), diabetes (HR 0.35, p=0.020), and baseline ABI below 0.44 (HR 0.31, p=0.019) were associated with a reduced probability of clinical improvement. CONCLUSION: Certain patients with intermittent claudication show substantial clinical improvement with conservative medical therapy, despite any lack of hemodynamic improvement. Given the low number of patients with clinical deterioration in the short term, primarily conservative therapy should be the preferred initial option for most claudicants.