Renal function and long-term mortality in patients with asymptomatic carotid atherosclerosis.

Renal dysfunction is a risk factor for mortality in patients with atherosclerosis. Estimated glomerular filtration rate (eGFR), cystatin C (CysC) and beta-2-microglobulin (B2M) are measures of renal function. It remains unclear, which of these parameters is the strongest predictor of outcome in patients with atherosclerosis. All-cause and cardiovascular mortality were prospectively investigated in 1,065 consecutive patients with asymptomatic carotid atherosclerosis. During a median follow-up of 6.3 years 275 patients died (25.8%), including 182 (66.2%) from cardiovascular causes. Estimated GFR, CysC and B2M were all significantly and independently associated with mortality. Inclusion of the renal parameters CysC and B2M but not of eGFR into a model with established cardiovascular risk factors improved the C-statistics significantly (p=0.0035 and 0.036, respectively; p=0.182 for eGFR). The net reclassification improvement (NRI) was 32.4% (p<0.0001) for CysC, 29% (p<0.0001) for B2M, and 16.5% (p=0.019) for eGFR. The integrated discrimination improvement (IDI) was 0.014 (p=0.0009) for CysC and 0.011 (p=0.005) for B2M while it was not significant for eGFR. Results were consistent for various subgroups with different extent of atherosclerosis. In summary, CysC and B2M were found to be independent predictors for mortality and had superior predictive value compared to eGFR in patients with asymptomatic carotid atherosclerosis. The clinical importance of these findings has to be validated in larger studies with a community-based approach.

The prognostic impact of soluble apoptosis-stimulating fragment on mortality in patients with carotid atherosclerosis.

BACKGROUND AND PURPOSE: Markers of apoptosis are associated with cardiovascular disease. The soluble apoptosis-stimulating fragment (sFAS) was found to be a predictor for outcome in patients with heart failure, but its importance in patients with atherosclerotic disease has not been fully understood as yet. The aim of the present study was to investigate the impact of sFAS on all-cause and cardiovascular mortality in patients with atherosclerosis in the carotid arteries. METHODS: We studied 981 of 1286 consecutive patients with neurological asymptomatic carotid atherosclerosis as evaluated by duplex Doppler sonography. Patients were prospectively followed for long-term all-cause and cardiovascular mortality. RESULTS: During a median follow-up of 6.2 years (interquartile range, 5.9 to 6.6 years), a total of 250 deaths (25.5%), including 165 (66%) cardiovascular deaths, were recorded. The risk for all-cause and for cardiovascular mortality, respectively, increased significantly with sFAS concentrations (P<0.001). The hazard ratio for all-cause death was elevated by 2.3-fold (P<0.001) and for cardiovascular death by 2.4-fold (P<0.001) in patients within the highest quintile of sFAS compared with patients within the lowest quintile, respectively. Results remained significant after adjustment for potential confounders and established cardiovascular risk factors, including high-sensitivity C-reactive protein. Patients with high sFAS but low high-sensitivity C-reactive protein had a comparable survival rate with those with elevated high-sensitivity C-reactive protein only (P=0.50). CONCLUSIONS: Markers of apoptosis, as measured by sFAS, were found to be independent risk predictors for death in patients with atherosclerotic disease in the carotid arteries.

Beta 2 microglobulin and the risk for cardiovascular events in patients with asymptomatic carotid atherosclerosis.

BACKGROUND AND PURPOSE: Atherosclerosis is a chronic inflammatory disease. Ongoing inflammation is associated with elevated levels of beta 2 microglobulin (B2M). We investigated B2M levels in a large cohort of patients with carotid atherosclerosis for the occurrence of major adverse cardiovascular events. METHODS: One thousand five of 1286 consecutive, neurologically asymptomatic patients with carotid atherosclerosis were followed for a median of 3 years (interquartile range, 2.5 to 3.5) for the occurrence of major adverse cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary bypass graft, stroke, and death. RESULTS: We recorded 359 major cardiovascular events in 271 (27%) patients. B2M was significantly associated with the occurrence of major adverse cardiovascular events. With increasing quartiles of B2M, the adjusted hazard ratios were 1.19 (95% CI, 0.81 to 1.73), 1.51 (95% CI, 1.05 to 2.18), and 1.88 (95% CI, 1.26 to 2.79) compared with the lowest quartile, respectively (P<0.001). Adjusted hazard ratios for the occurrence of death, myocardial infarction, and stroke for increasing quartiles of B2M were 1.25 (95% CI, 0.92 to 1.70), 1.52 (95% CI, 1.12 to 2.06), and 1.62 (95% CI, 1.16 to 2.67) compared with the lowest quartile, respectively (P<0.001). Through statistical estimation of improvement in risk stratification, addition of B2M to baseline risk factors improved the risk stratification for major cardiovascular events, at least as much as high-sensitivity C-reactive protein or even better. CONCLUSIONS: B2M was independently and significantly associated with adverse cardiovascular outcome in patients with prevalent asymptomatic carotid atherosclerosis.

Cystatin C and the risk for cardiovascular events in patients with asymptomatic carotid atherosclerosis.

BACKGROUND AND PURPOSE: Renal dysfunction is a risk factor for cardiovascular events in patients with atherosclerosis. Unlike serum creatinine or estimated glomerular filtration rate, cystatin C reflects renal dysfunction independent of factors such as sex, weight, and race. We investigated whether baseline serum levels of cystatin C predict major cardiovascular events in patients with asymptomatic carotid atherosclerosis and compared the predictive value of cystatin C to these established markers of renal function. METHODS: We prospectively studied 1004 of 1286 consecutive patients with carotid ultrasound scanning. Patients were followed for the occurrence of major cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary bypass graft, stroke, and death. RESULTS: During a median of 3 years of follow-up, we recorded 346 major cardiovascular events in 311 patients. The risk for a first major cardiovascular event increased significantly with increasing quintiles of cystatin C; hazard ratios ranged from 1.18 to 1.94 for the highest versus the lowest quintile (P<0.001 for trend). Creatinine levels showed no significant association with major cardiovascular events, and for glomerular filtration rate, only the lowest quintile was moderately associated with adverse cardiovascular outcome. CONCLUSIONS: Cystatin C was significantly and gradually associated with future cardiovascular events in patients with carotid atherosclerosis. In contrast, neither serum creatinine nor estimated glomerular filtration rate were significant predictors of adverse cardiovascular outcomes.

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

OBJECTIVES: We hypothesized that high sensitivity C-reactive protein (hs-CRP) and the presence of renal artery stenosis (RAS) might conjointly predict future major adverse cardiovascular events (MACE) in patients with peripheral artery disease (PAD). BACKGROUND: Clinical outcome in PAD is determined by the extent of atherosclerosis affecting additional vascular beds and the activity of the atherosclerotic process reflected by inflammatory serum markers. Data on the predictive value of hs-CRP on outcome in PAD patients with RAS is limited. METHODS: We prospectively enrolled 447 PAD patients who were admitted to our institution for angioplasty. Preintervention hs-CRP was assessed and renal angiograms were obtained. Patients were then followed clinically for the occurrence of MACE for median 15.6 months. Serum creatinine was obtained in all patients at 12 months. RESULTS: Incidental RAS >or=60% at baseline was found in 68 patients (15.2%), MACE were recorded in 111 patients during follow-up. Hs-CRP was significantly associated with the occurrence of MACE (p<0.001) and with 12 months creatinine levels (p=0.005). Adjusted hazard ratios for MACE for increasing quartiles of hs-CRP as compared to the lowest quartile were 1.11 (95% CI 0.53-2.35), 1.06 (95% CI 0.50-2.26) and 2.79 (95% CI 1.47-5.28). Analyzing joint effects of hs-CRP and RAS, we observed no significant interaction. CONCLUSION: Hs-CRP predicts cardiovascular and renal outcome in PAD patients irrespective of the presence of RAS. Patients with hs-CRP levels above 0.88 mg/dL were at particularly high risk for MACE.

Complications after peripheral vascular interventions in octogenarians.

PURPOSE: To investigate the incidence of complications after peripheral vascular interventions in patients aged 80 years and older compared to patients below the age of 80. METHODS: During a 20-month period, 619 consecutive patients (354 men; mean age 67 years, range 59-87) undergoing balloon angioplasty and stenting for lower limb revascularization were enrolled in the study. The incidence of procedure-related, access-site, and major complications within 30 days post intervention were recorded and compared between patients aged 80 years and older (n=72, 11.6%) and those under 80 years of age. RESULTS: Complication rates were significantly higher in octogenarians compared to patients below 80 years, including the rates of overall complications (18.1% versus 8.5%, p=0.010), major complications (11.1% versus 1.8%, p<0.001), all access site complications (12.5% versus 4.9%, p=0.009), and access site bleeding complications (12.5% versus 2.2%, p<0.001). By multivariable analysis, octogenarians had a 2.49-fold increased adjusted risk (95% CI 1.10 to 5.65, p=0.029) for any postintervention complication and a 10.99-fold increased adjusted risk (95% CI 2.76 to 45.74, p=0.001) for major complications compared to patients below 80 years. No specific risk factor for complications or major complications within the octogenarian population could be identified. CONCLUSION: Patients aged 80 years and older have a dramatically increased risk, particularly for major complications, after peripheral vascular interventions. Identification of risk factors and development of preventive strategies are urgently needed to improve procedure safety in this extremely vulnerable population.

Increasing carotid plaque echolucency is predictive of cardiovascular events in high-risk patients.

PURPOSE: Carotid plaque echolucency seen at ultrasonography (US) is a potential indicator of plaque instability and may help identify patients at risk for major adverse cardiovascular events (MACEs). The authors performed this study to determine whether decreasing gray-scale median (GSM) levels at repeat carotid US examinations are associated with future MACEs. MATERIALS AND METHODS: The study was approved by the institutional ethics committee and all patients provided informed consent. The authors prospectively studied 574 patients with carotid plaques of at least 30% from a group of 1268 consecutive patients who were initially asymptomatic with respect to carotid disease. GSM levels were determined with carotid US at baseline and after a median of 7.5 months (range, 6-9 months), and the mean change of the GSM was calculated. Patients were then followed up clinically for a median of 3.2 years for the occurrence of composite MACE. RESULTS: During the initial period, the median change in carotid GSM was 2.9 (interquartile range [IQR], -6.9 to 11.0). Of 574 study participants, 230 (40%) showed a reduction of GSM levels and 344 (60%) showed an increase. MACEs were observed in 177 (31%) of the 574 patients. Adjusted hazard ratios for the lowest quartile (GSM change less than -6.9), the second quartile (GSM change between -6.9 and 2.9), and the third quartile (GSM change between 3.0 and 11.0) were 1.71 (95% confidence interval [CI]: 1.09, 2.66), 1.36 (95% CI: 0.86, 2.16), and 1.22 (95% CI: 0.77, 1.95), respectively, compared with the highest quartile (GSM change greater than 11.0) (P = .018). CONCLUSION: Increasing echolucency of carotid artery plaques within a 6- to 9-month interval is predictive of midterm clinical adverse events of atherosclerosis.

Conventional balloon angioplasty versus peripheral cutting balloon angioplasty for treatment of femoropopliteal artery in-stent restenosis: initial experience.

PURPOSE: To prospectively determine whether cutting balloon angioplasty, when compared with conventional balloon angioplasty (CBA), improves morphologic and clinical outcome in patients with femoropopliteal in-stent restenosis. MATERIALS AND METHODS: Patients with symptomatic femoropopliteal in-stent restenosis were randomly assigned to undergo CBA or peripheral cutting balloon angioplasty (PCBA) for treatment of lesions up to 20 cm in length. Patients were followed up clinically and with duplex ultrasonography (US) at 1, 3, and 6 months for occurrence of a restenosis of 50% or higher. The Fisher exact test and Mann Whitney U test were used for statistical analyses. RESULTS: Forty patients were enrolled; one patient was lost to follow-up. In the remaining patients, CBA was performed in 22 patients; PCBA was used in 17 patients. Average lesion length was 80 mm +/- 68 (standard deviation). Restenosis rates at 6 months were 65% (11 of 17; 95% confidence interval: 42%, 88%) after PCBA versus 73% (16 of 22; 95% confidence interval: 54%, 92%) after CBA (P = .73). Ankle brachial index (0.83 vs 0.75, P = .26) and maximum walking capacity on the treadmill (117 m vs 103 m, P = .97) at 6 months were also not significantly different between the two groups. CONCLUSION: PCBA failed to prove superiority compared with CBA for treatment of femoropopliteal in-stent restenosis in this pilot study. In restenotic lesions with an average length of approximately 8 cm, both treatment modalities yielded disappointing 6-month patency rates.

De novo superficial femoropopliteal artery lesions: peripheral cutting balloon angioplasty and restenosis rates--randomized controlled trial.

PURPOSE: To prospectively determine, in a randomized controlled trial, whether cutting balloon angioplasty (CBA) yields superior morphologic and clinical outcomes at 6 months compared with the 6-month outcomes after conventional percutaneous transluminal angioplasty (PTA) in patients with short de novo superficial femoropopliteal artery (SFA) lesions. MATERIALS AND METHODS: This study was approved by the ethics committees of the two participating centers, and informed consent was obtained from all patients. The authors randomly assigned 43 patients (26 men, 17 women; median age, 69 years) who had 5 cm or shorter de novo SFA lesions in association with intermittent claudication or chronic limb ischemia to undergo CBA or PTA. The patients were followed up clinically, and restenosis was assessed with duplex ultrasonography (US) at 6 months. chi(2) and Mann-Whitney U tests were used to compare data between the two treatment groups. RESULTS: The US-determined 6-month restenosis rate was 32% (seven patients) in the PTA group versus 62% (13 patients) in the CBA group (P = .048). Sixteen (73%) PTA group patients versus eight (38%) CBA group patients were asymptomatic at follow-up (P = .059). There was no significant difference in ankle-brachial index (median, 0.83 vs 0.77 for PTA vs CBA group, respectively; P = .56) or pain-free walking distance (median, >1000 m vs 600 m for PTA vs CBA group, respectively; P = .17) between the two groups. CONCLUSION: CBA did not prove to be superior to conventional PTA for treatment of short de novo SFA lesions and yielded increased restenosis rates at 6 months.

Progression of carotid stenosis detected by duplex ultrasonography predicts adverse outcomes in cardiovascular high-risk patients.

BACKGROUND AND PURPOSE: The progression of carotid stenosis reflects the activity of atherosclerotic disease and may indicate a risk for systemic atherothrombotic complications. We investigated whether progressive carotid stenosis determined by duplex ultrasonography predicts adverse outcomes in cardiovascular high-risk patients. METHODS: We prospectively studied 1065 of 1268 consecutive patients initially asymptomatic with respect to carotid disease. Carotid ultrasound investigations at baseline and after a median of 7.5 months (range, 6 to 9 months) were performed to identify patients with progressive stenosis as defined by Doppler velocity criteria. Patients were then followed up clinically for a median of 3.2 years for the occurrence of major adverse cardiovascular events (composite MACEs: myocardial infarction, percutaneous coronary or peripheral interventions, coronary or vascular surgery, amputation, stroke, and all-cause mortality). RESULTS: We found progressive carotid stenosis in 93 patients (9%) by ultrasound and thereafter recorded 495 MACEs in 421 patients (40%) during clinical follow-up. Patients with progressive carotid stenosis had a significantly increased risk for cardiovascular events compared with patients with nonprogressive disease: adjusted hazard ratios and confidence intervals were 2.01 for composite MACEs (95% CI, 1.48 to 2.67, P<0.001), 2.38 for myocardial infarction (95% CI, 1.07 to 5.35, P=0.044), 1.59 for any coronary event (95% CI, 1.10 to 2.28, P=0.011), 2.00 for stroke (95% CI, 1.02 to 4.11, P=0.035), 2.42 for any peripheral vascular event (95% CI, 1.61 to 3.62, P<0.001), and 1.75 for cardiovascular death (95% CI, 1.03 to 2.97, P=0.039). CONCLUSIONS: Progression of carotid stenosis within a 6- to 9-month interval detected by duplex ultrasound predicts midterm clinical adverse events of atherosclerosis in high-risk patients affecting the coronary, cerebrovascular, and peripheral circulations.

Quality of life after balloon angioplasty versus stent implantation in the superficial femoral artery: findings from a randomized controlled trial.

PURPOSE: To investigate whether primary nitinol stenting in the superficial femoral artery (SFA) is beneficial to patients' quality of life (QoL). METHODS: One hundred four patients (55 men; mean age 66+/-19 years) with chronic limb ischemia and SFA disease were randomly assigned to primary stent implantation (n=51) or balloon angioplasty (n=53) with optional stenting for a suboptimal angioplasty result (17 of 53). QoL was measured by the SF-36 questionnaire at baseline and at 3, 6, and 12 months post intervention. RESULTS: QoL was significantly improved post intervention and up to 12 months in both treatment groups. Significant inverse associations were observed between QoL parameters and restenosis. Comparing primary stenting (n=51) versus balloon angioplasty with optional stenting (n=53) by the intention to treat, no significant differences in QoL were observed. Analyses of stented patients (n=68) versus balloon angioplasty (n=36) patients, however, demonstrated significantly improved measures of QoL after stenting. CONCLUSION: Endovascular revascularization of SFA disease improves QoL, and restenosis negatively affects QoL outcomes. After stent implantation, whether primary or secondary, QoL was significantly ameliorated compared to balloon angioplasty alone. However, it remains to be proven in larger cohorts whether primary stenting yields a QoL benefit compared to balloon angioplasty with optional secondary stenting.

Duplex sonography versus angiography for assessment of femoropopliteal arterial disease in a "real-world" setting.

PURPOSE: To evaluate the agreement of duplex ultrasound (DUS) versus digital subtraction angiography (DSA) for assessment of femoropopliteal arterial disease in a real-world clinical setting. METHODS: Consecutive patients with peripheral artery disease who were scheduled for a percutaneous intervention were included in this retrospective study. During an 18-month period, 491 patients (276 men; median age 73 years, interquartile range 64-81) were enrolled. A peak systolic velocity ratio (PSVR)>2.4 was the optimal cutoff for detecting a >50% stenosis by DSA. Findings of preprocedural DUS in the proximal, middle, and distal ipsilateral superficial femoral artery and in the popliteal segment were analyzed for agreement with preprocedural femoropopliteal DSA using kappa statistics. Only the target limb in each patient was analyzed, for a total of 1964 vascular segments. RESULTS: Agreement for the degree of stenosis in 10% increments was only moderate (weighted kappa 0.67, 95% CI 0.65 to 0.69). Using the PSVR>2.4 cutoff, agreement between DUS and DSA for a >50% stenosis was good (kappa 0.79, 95% CI 0.77 to 0.81). Sensitivity, specificity, positive predictive value, and negative predictive value for correctly detecting a >50% stenosis by DUS were 0.81 (0.78 to 0.84), 0.93 (0.91 to 0.94), 0.84 (0.81 to 0.87), and 0.91 (0.87 to 0.95), respectively. Comparable findings were observed within different patient subgroups. CONCLUSION: Agreement between DUS and DSA in the femoropopliteal segment is only moderate with respect to the absolute degree of stenosis. However, detection of a >50% stenosis can be done with acceptable precision in routine clinical practice using PSVR>2.4 as a threshold.

Sustained benefit at 2 years of primary femoropopliteal stenting compared with balloon angioplasty with optional stenting.

BACKGROUND: Primary stenting with self-expanding nitinol stents of the superficial femoral artery yielded improved morphological and clinical results compared with balloon angioplasty with optional stenting until 12 months in a randomized controlled trial. We now report 2-year data on restenosis and clinical outcomes of these patients. METHODS AND RESULTS: Of 104 patients with chronic limb ischemia and superficial femoral artery obstructions, 98 (94%) could be followed up until 2 years after intervention for occurrence of restenosis (>50%) by duplex ultrasound and for clinical and hemodynamic outcome by treadmill walking distance and ankle brachial index. Restenosis rates at 2 years were 45.7% (21 of 46) versus 69.2% (36 of 52) in favor of primary stenting compared with balloon angioplasty with optional secondary stenting by an intention-to-treat analysis (P=0.031). Consistently, stenting (whether primary or secondary; n=63) was superior to plain balloon angioplasty (n=35) with respect to the occurrence of restenosis (49.2% versus 74.3%; P=0.028) by a treatment-received analysis. Clinically, patients in the primary stent group showed a trend toward better treadmill walking capacity (average, 302 versus 196 m; P=0.12) and better ankle brachial index values (average, 0.88 versus 0.78; P=0.09) at 2 years, respectively. Reintervention rates tended to be lower after primary stenting (17 of 46 [37.0%] versus 28 of 52 [53.8%]; P=0.14). CONCLUSIONS: At 2 years, primary stenting with self-expanding nitinol stents for the treatment of superficial femoral artery obstructions yields a sustained morphological benefit and a trend toward clinical benefit compared with balloon angioplasty with optional stenting.

C-reactive protein predicts future cardiovascular events in patients with carotid stenosis.

BACKGROUND AND PURPOSE: Atherosclerosis is a systemic inflammatory disease. We demonstrated previously that high-sensitivity C-reactive protein (hs-CRP) is associated with short-term progression of carotid atherosclerosis. We now investigated whether baseline levels of hs-CRP predict midterm clinical outcome in these patients. METHODS: We prospectively studied 1065 of 1268 consecutive patients who were initially asymptomatic with respect to carotid artery disease and were investigated with serial carotid ultrasound examinations at baseline and after a 6- to 9-month interval. Patients were followed-up clinically for the occurrence of cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, and death. RESULTS: We recorded progression of carotid stenosis in 93 patients (9%) after 6 to 9 months, and 381 cardiovascular events in 337 patients (27%) during a median of 3 years of clinical follow-up (interquartile range, 2.5 to 3.5 years). The hs-CRP levels were significantly elevated in patients with progressive carotid stenosis (P<0.001), and hs-CRP was significantly associated with the occurrence of a first future cardiovascular event (P<0.001). Adjusted hazard ratios for a first cardiovascular event for increasing quintiles of hs-CRP were 1.41 (95% confidence interval, 0.92 to 2.17), 1.76 (95% confidence interval, 1.17 to 2.66), 2.22 (95% confidence interval, 1.48 to 3.32), and 2.41 (95% confidence interval, 1.61 to 3.60) as compared with the lowest quintile, respectively. This association was independent of traditional cardiovascular risk factors and the baseline degree of carotid stenosis. CONCLUSIONS: Inflammation was associated with morphological and clinical progression of atherosclerotic disease. Patients with elevated levels of hs-CRP exhibit an increased risk for adverse cardiovascular outcome attributable to clinical adverse events of progressive atherosclerotic disease.

Complement component C5a predicts restenosis after superficial femoral artery balloon angioplasty.

PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates.

Dental and periodontal status and risk for progression of carotid atherosclerosis: the inflammation and carotid artery risk for atherosclerosis study dental substudy.

BACKGROUND AND PURPOSE: Dental and periodontal disease are potentially involved in the pathogenesis of atherosclerosis. We investigated whether dental and periodontal status is associated with the presence and future progression of carotid stenosis. METHODS: We randomly selected 411 of 1268 participants from the prospective Inflammation and Carotid Artery Risk for Atherosclerosis Study and evaluated dental and periodontal status and oral hygiene at baseline measuring three World Health Organization-validated indices: DMFT (decayed, missing, filled teeth), SLI (Silness-Löe Index), and CPITN (community periodontal index for treatment needs), respectively. The degree of carotid stenosis was measured by duplex ultrasound at baseline and after median 7.5 months (range=6 to 9 months) to identify patients with progressive carotid stenosis. RESULTS: DMFT (P<0.01), SLI (P=0.048), CPITN (P=0.007), and edentulousness (P=0.007) were associated with the baseline degree of carotid stenosis. Atherosclerosis progression was observed in 48 of 411 patients (11.7%). DMFT (adjusted odds ratio [OR]=1.11, 95% CI=1.01 to 1.22, P=0.032) and SLI (adjusted OR=1.77, 95% CI=1.09 to 2.79, P=0.021), but not CPITN (adjusted OR=1.51, 95% CI=0.89 to 2.45, P=0.16) were significant predictors of disease progression, irrespective of traditional cardiovascular risk factors and the baseline degree of stenosis. Edentulous patients had a significantly increased risk for disease progression as compared with patients with teeth (adjusted OR=2.10, 95% CI=1.06 to 4.16, P=0.33). CONCLUSIONS: Dental status, oral hygiene, and particularly tooth loss are associated with the degree of carotid stenosis and predict future progression of the disease.

Asymmetric dimethylarginine predicts major adverse cardiovascular events in patients with advanced peripheral artery disease.

OBJECTIVE: Circulating concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, are elevated in conditions associated with increased cardiovascular risk. We investigated whether elevated ADMA concentrations predict major adverse cardiovascular events (MACE) in patients with advanced peripheral artery disease (PAD). METHODS AND RESULTS: We prospectively enrolled 496 of 533 consecutive patients with PAD (median age 70 years, 279 males). ADMA and L-arginine were assessed at baseline by high performance liquid chromatography. The occurrence of MACE (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, carotid revascularization, death) was evaluated during a follow-up of median 19 months (interquartile range 11 to 25). One hundred eighty-two MACE were observed in 141 patients (28%). MACE occurred in 39% of the patients in the highest quartile and 26% of those in the lowest quartile of ADMA (P=0.016, log-rank test for all quartiles). Adjusted hazard ratios for occurrence of MACE for increasing quartiles of ADMA compared with the lowest quartile were 0.87 (95% confidence interval [CI], 0.51 to 1.48), 1.12 (95% CI, 0.62 to 1.90), and 1.70 (95% CI, 1.02 to 2.88), respectively. We observed no association between cardiovascular outcome and L-arginine. CONCLUSIONS: High ADMA plasma concentrations independently predict MACE in patients with advanced PAD. This indicates that ADMA may be a new cardiovascular risk marker in these patients.

Myeloperoxidase predicts progression of carotid stenosis in states of low high-density lipoprotein cholesterol.

OBJECTIVES: We investigated the effect of myeloperoxidase (MPO) on progression of carotid stenosis in states of high and low high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels. BACKGROUND: Myeloperoxidase is pivotally involved in the pathogenesis of atherosclerosis. In vitro data suggest that MPO exerts deleterious effects via oxidative modulation of lipoproteins. METHODS: We prospectively studied 1,019 of 1,268 consecutive patients who were asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of median 7.5 months (range 6 to 9 months), categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. The MPO, HDL-C, and LDL-C levels were measured at baseline, grouped by medians, and correlated with progression of carotid atherosclerosis. RESULTS: Progression of carotid atherosclerosis was found in 100 of 1,019 patients (9.8%). Myeloperoxidase (p = 0.014) but not HDL-C (p = 0.95) or LDL-C (p = 0.30) were associated with progressive disease. However, MPO > or =310 ng/ml was significantly associated with progressive disease (adjusted odds ratio [OR] 2.57, 95% confidence interval [CI] 1.39 to 4.75) only in patients with HDL-C levels <49 mg/dl. Otherwise, in patients with higher HDL-C levels (> or =49 mg/dl), MPO > or =310 ng/ml did not predict disease progression (adjusted OR 1.42, 95% CI 0.72 to 2.78). No interaction of MPO with LDL-C was observed. CONCLUSIONS: Myeloperoxidase was associated with progression of carotid atherosclerosis in patients with HDL cholesterol levels below 49 mg/dl.

Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery.

BACKGROUND: Because stent implantation for disease of the superficial femoral artery has been associated with high rates of late clinical failure, percutaneous transluminal angioplasty is preferred for endovascular treatment, and stenting is recommended only in the event of suboptimal technical results. We evaluated whether primary implantation of a self-expanding nitinol (nickel-titanium) stent yielded anatomical and clinical benefits superior to those afforded by percutaneous transluminal angioplasty with optional secondary stenting. METHODS: We randomly assigned 104 patients who had severe claudication or chronic limb ischemia due to stenosis or occlusion of the superficial femoral artery to undergo primary stent implantation (51 patients) or angioplasty (53 patients). Restenosis and clinical outcomes were assessed at 6 and 12 months. RESULTS: The mean (+/-SD) length of the treated segment was 132+/-71 mm in the stent group and 127+/-55 mm in the angioplasty group. Secondary stenting was performed in 17 of 53 patients (32 percent) in the angioplasty group, in most cases because of a suboptimal result after angioplasty. At 6 months, the rate of restenosis on angiography was 24 percent in the stent group and 43 percent in the angioplasty group (P=0.05); at 12 months the rates on duplex ultrasonography were 37 percent and 63 percent, respectively (P=0.01). Patients in the stent group were able to walk significantly farther on a treadmill at 6 and 12 months than those in the angioplasty group. CONCLUSIONS: In the intermediate term, treatment of superficial-femoral-artery disease by primary implantation of a self-expanding nitinol stent yielded results that were superior to those with the currently recommended approach of balloon angioplasty with optional secondary stenting. (ClinicalTrials.gov number, NCT00281060.).