Unused potential of lipid-lowering therapy in very high-risk patients with atherosclerotic cardiovascular disease. A retrospective data analysis.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in Europe. Although the 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the management of dyslipidaemias claim a target low-density lipoprotein cholesterol (LDL-C) value of <55 mg/dL for very high-risk patients by use of lipid-lowering therapy (LLT) and lifestyle adaptations, the target level achievement is not satisfactory. We examined LLT use in ASCVD patients exceeding LDL-C target levels at admission and its adaptations at discharge. METHODS AND RESULTS: Between January 2017 and February 2020, 1091 patients with LDL-C >100 mg/dL and ASCVD defined as diagnosis of angina pectoris (AP, n = 179), acute myocardial infarction (AMI, n = 317), chronic ischemic heart disease (CHD, n = 195), or peripheral artery disease (PAD, n = 400) were extracted from hospital records. LLT use on admission and discharge as well as recommendations on lifestyle and nutrition were analysed. On admission, 51% of the patients were not taking LLT. At discharge, 91% were prescribed statins and 87% were advised on lifestyle adaptation and/or pharmacological treatment. High-intensity statin use at discharge was present in 63% of the AP-group, 92% of the AMI-group, 62% of the CHD-group and 71% of the PAD-group. Ezetimibe was present in 16% and proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) in 1%. However, of those on high-intensity statin, 25% remained on insufficient statin dosage. CONCLUSION: Switch to high-intensity statins and use of ezetimibe and PCSK9i was low in chronic ASCVD patients. Even though statin intake was high in high-risk patients, target levels were still not reached.

Secondary Prevention in Lower Extremity Artery Disease Patients: Lipid-Lowering Therapy and Long-Term Guideline Adherence.

Lower extremity artery disease (LEAD) affects millions of elderly patients and is associated with elevated cardiovascular morbidity and mortality. Risk factor modification, including the therapy of dyslipidaemia, is mandatory to reduce cardiovascular event rates and to improve survival rates. However, only a minority achieve the recommended low-density lipoprotein cholesterol (LDL-C) target level < 55 mg/dL, according to the current ESC/EAS guidelines on the treatment of dyslipidaemia. This study elucidated the implementation of the lipid-lowering guideline recommendations of 400 LEAD patients with LDL-C > 100 mg/dL and their adherence to treatment adjustment during follow-up. Despite a sustained statin prescription in 93% of the patients, including 77% with high-intensity statins at follow-up, only 18% achieved the target level. Ezetimibe appeared in 21% and LDL-C goals were reached significantly more often with combination therapy. Recurrent revascularization appeared more often (28%) than coronary artery or cerebrovascular disease progression (14%) and 7% died. Despite the frequent use of high-intensity statins and expandable rates of ezetimibe, the progression of cardiovascular events remained inevitable. Only 18% of the patients had received recommendations on lifestyle modification, including dietary adaptations, which is key for a holistic approach to risk factor control. Thus, efforts for both pharmacological and behavioral strategies are needed to improve clinical outcomes and survival rates.

Access Site Related Vascular Complications following Percutaneous Cardiovascular Procedures.

Vascular access site complications (ASC) are among the most frequent complications of percutaneous cardiovascular procedures (PCP) and are associated with adverse outcome and high resources utilization. In this prospective study, we investigated patients with postprocedural clinical suspicion of ASC evaluated by duplex ultrasound (DUS) for the presence of ASC. We assessed the incidence, in-hospital outcome, treatment of complications and predictors for ASC. Overall, 12,901 patients underwent PCP during a 40 months period. Of those, 2890 (22.4%) patients had postprocedural clinical symptoms of ASC and were evaluated using DUS. An ASC was found in 206 of the DUS examined patients (corresponding to 7.1% of the 2890 DUS examined patients). In 6.7% of all valvular/TAVI procedures, an ASC was documented, while coronary, electrophysiological and peripheral PCP had a comparable and low rate of complications (1.2-1.5%). Pseudoaneurysm (PSA) was the most frequent ASC (67.5%), followed by arteriovenous fistula (13.1%), hematoma (7.8%) and others (11.7%). Of all PSA, 84 (60.4%) were treated surgically, 44 (31.6%) by manual compression and 11 (7.9%) conservatively. Three (0.02%) patients died due to hemorrhagic shock. In conclusion, femoral ASC are rare in the current era of PCP with PSA being the leading type of ASC. Nonetheless, patients with predisposing risk factors and postprocedural suspicious clinical findings should undergo a DUS to early detect and mitigate ASC-associated outcome.

Feasibility and impact of carbon dioxide angiography on acute kidney injury following endovascular interventions in patients with peripheral artery disease and renal impairment.

BACKGROUND: Post-contrast acute kidney injury (AKI) is a dreaded complication of endovascular revascularization using iodinated contrast medium in patients with peripheral artery disease and concomitant chronic kidney disease (CKD). This study sought to evaluate the incidence of AKI in patients with peripheral artery disease and CKD undergoing endovascular revascularization and using carbon dioxide (CO2) as contrast medium. METHODS AND RESULTS: From 04/2015 to 07/2018, all consecutive peripheral artery disease patients with CKD stage ≥ 3 referred for endovascular revascularization of symptomatic peripheral artery disease were prospectively included. During endovascular revascularization, CO2 as contrast medium was manually injected and iodinated contrast medium was additionally used when needed. The reference group consisted of 211 cardiovascular risk factor-matched patients undergoing endovascular revascularization with iodinated contrast medium only. CO2-guided endovascular revascularization was performed in 102 patients, thereof 16 (15.7%) patients exclusively with CO2. Baseline CKD stage ≥ 4 and iodinated contrast medium volume > 50 ml were disproportionally associated with post-procedural post-contrast AKI. At CKD stage 4 the odds ratio for post-contrast AKI was 13.2 (95% CI 1.489-117.004; p = 0.02) for iodinated contrast medium volume 51-100 ml and 37.7 (95% CI 3.927-362.234; p = 0.002) for iodinated contrast medium volume > 100 ml. The corresponding values at CKD stage 5 were 23.7 (95% CI 2.666-210.583; p = 0.005) and 28.3 (95% CI 3.289-243.252; p = 0.002), respectively. Radiation (dose area product) was significantly higher in the CO2-endovascular revascularization group (6.025 ± 6.926 cGy*cm2 vs. 4.281 ± 4.722 cGy*cm2, p = 0.009). CONCLUSION: CO2 is an applicable and safe alternative to iodinated contrast medium for endovascular revascularization in peripheral artery disease patients with concomitant CKD. Patients with CKD stage 4 or 5, being at highest risk for post-contrast AKI, should primarily be treated by CO2-guided endovascular revascularization.

[Medication-based secondary prevention in patients with peripheral arterial occlusive disease : An analysis based on secondary data]. / Medikamentöse Sekundärprävention bei Patienten mit peripherer arterieller Verschlusskrankheit : Eine sekundärdatenbasierte Analyse.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is an atherosclerotic vascular disease with high morbidity and mortality. A consistent medication-based secondary prevention is part of the essential and evidence-based treatment of PAOD. The aim of this study was to ascertain the status quo of medicinal secondary prevention based on submitted prescriptions. METHODS: In the time period from 2014 to 2017 patients with a confirmed PAOD coding (I70.2-/I73.9-) were identified based on secondary data of the Association of Statutory Health Insurance Physicians Westphalia-Lippe (KVWL). The prescriptions submitted with respect to platelet inhibitors, oral anticoagulants, lipid lowering therapy (LLT) and angiotensin-converting enzyme (ACE) inhibitors in the fourth quarter year after diagnosis coding were collated. RESULTS: In the diagnosis period 2014/2015 a total of 238,397 patients had PAOD in the catchment area of the KVWL. The proportion of submitted prescriptions in the fourth quarter year after diagnosis was 25.9% for LLT, 13.6% for acetylsalicylic acid, 4.5% for clopidogrel, 5.5% for vitamin K antagonists (VKA), 3.5% for non-vitamin K­dependent oral anticoagulants (NOAC) and 26.8% for ACE inhibitors. Over the course of the 3 years (n = 241,375 patients with PAOD 2016/2017) the proportion of submitted prescriptions for all substances except VKA increased (p < 0.001), whereby the largest relative increase was noted for NOAC (relative increase of 81.7%). CONCLUSION: The guideline-conform medicinal secondary prevention in patients with PAOD in Germany is still in need of improvement. A consistent implementation of evidence-based medicinal secondary prevention harbors a great potential for improvement of the overall prognosis in patients with PAOD.

Outcome of patients with chronic limb-threatening ischemia with and without revascularization.

Background: Patients with chronic critical limb-threatening ischemia (CLTI) are at high risk of amputation and death. Despite the general recommendation for revascularization in CTLI in the guidelines, the underlying evidence for such a recommendation is limited. The aim of our study was to assess the outcome of patients with CLTI depending on the use of revascularization in a retrospective real-world cohort. Patients and methods: Administrative data of the largest German Health insurance (BARMER GEK) were provided for all patients that were hospitalized for the treatment of CLTI Rutherford category (RF) 5 and 6 between 2009 and 2011. Patients were followed-up until December 31st, 2012 for limb amputation and death in relation to whether patients did (Rx +) or did not have (Rx -) revascularization during index-hospitalization. Results: We identified 15,314 patients with CLTI at RF5 (n = 6,908 (45.1%)) and RF6 (n = 8,406 (54.9%)), thereof 7,651 (50.0%) underwent revascularization (Rx +) and 7,663 (50.0%) were treated conservatively (Rx -). During follow-up (mean 647 days; 95% CI 640-654 days) limb amputation (46.5% Rx- vs. 40.6% Rx+, P < 0.001) and overall mortality (48.2% Rx- vs. 42.6% Rx+, P < 0.001) were significantly lower in the subgroup Rx+. Conclusions: In a real-world setting, only half of CLTI were revascularized during the in-hospital treatment. Though, revascularization was associated with significantly better observed short- and long-term outcome. These data do not allow causal conclusion due to lack of data on the underlying reason for applied or withheld revascularization and therefore may involve a relevant selection bias.

Unmet medical needs in intermittent Claudication with diabetes and coronary artery disease-A "real-world" analysis on 21 197 PAD patients.

BACKGROUND: Peripheral artery disease (PAD) is frequently co-prevalent with coronary artery disease (CAD) and diabetes (DM). The study aims to define the burden of CAD and/ or DM in PAD patients at moderate stages and further to evaluate its impact on therapy and outcome. METHODS: Study is based on health insurance claims data of the BARMER reflecting an unselected "real-world" scenario. Retrospective analyses were based on 21 197 patients hospitalized for PAD Rutherford 1-3 between 1 January 2009 to 31 December 2011, including a 4-year follow-up (median 775 days). RESULTS: In PAD patients, CAD is prevalent in 25.3% (n = 5355), DM in 23.5% (n = 4976), and both CAD and DM in 8.2% (n = 1741). Overall, in-hospital mortality was 0.4%, being increased if CAD was present (CAD alone: OR 1.849; 95%-CI 1.066-3.208; DM alone: OR 1.028; 95%-CI 0.520-2.033; CAD and DM: OR 3.115; 95%-CI 1.720-5.641). Both, CAD and DM increased long-term mortality (CAD alone: HR 1.234; 95%-CI 1.106-1.376; DM alone: HR 1.260; 95%-CI 1.125-1.412; CAD and DM: HR 1.76; 95%-CI 1.552-1.995). DM further increased long-term amputation risk (DM alone: HR 2.238; 95%-CI 1.849-2.710; DM and CAD: HR 2.199; 95%-CI 1.732-2.792), whereas CAD (alone) did not. CONCLUSIONS: In a greater perspective, the data identify also mild to modest stage PAD patients at particular risk for adverse outcomes in presence of CAD and/or DM. CAD and DM both are related with a highly increased risk of long-term mortality even in intermittent claudication, and DM independently increased amputation risk.

Impact of diabetes type on treatment and outcome of patients with peripheral artery disease.

BACKGROUND: The prevalence of diabetes mellitus and its associated complications such as peripheral artery disease is increasing worldwide. We aimed to explore the distinct impact of type 1 diabetes mellitus and type 2 diabetes mellitus on treatment and on short- and long-term outcome in patients with peripheral artery disease. METHODS: Retrospective analysis of anonymized data of hospitalized patients covered by a large German health insurance. Assessment of patient's characteristics (comorbidities, complications, etc.) and outcome using multivariable Cox regression and Kaplan-Meier curves. RESULTS: Among 41,702 patients with peripheral artery disease, 339 (0.8%) had type 1 diabetes mellitus and 13,151 (31.5%) had type 2 diabetes mellitus. Patients with diabetes mellitus had more comorbidities and complications than patients without diabetes mellitus ( p < 0.001). Type 1 diabetes mellitus patients exhibited the highest risk for limb amputation at 4-year follow-up (44.6% vs 35.1%, p < 0.001), while type 2 diabetes mellitus patients had higher mortality than type 1 diabetes mellitus (43.6% vs 31.0%, p < 0.001). CONCLUSION: Although the fraction of type 1 diabetes mellitus among patients with peripheral artery disease and diabetes mellitus is low, it represents a subset of patients being at particular high risk for limb amputation. Research focused on elaborating the determinants of limb amputation and mortality in peripheral artery disease patients with diabetes mellitus is warranted to improve the poor prognosis of these patients.

Association of CKD with Outcomes Among Patients Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND AND OBJECTIVES: Despitethe multiple depicted associations of CKD with reduced cardiovascular and overall prognoses, the association of CKD with outcome of patients undergoing transcatheter aortic valve implantation has still not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from all hospitalized patients who underwent transcatheter aortic valve implantation procedures between January 1, 2010 and December 31, 2013 in Germany were evaluated regarding influence of CKD, even in the earlier stages, on morbidity, in-hospital outcomes, and costs. RESULTS: A total of 28,716 patients were treated with transcatheter aortic valve implantation. A total of 11,189 (39.0%) suffered from CKD. Patients with CKD were predominantly women; had higher rates of comorbidities, such as coronary artery disease, heart failure at New York Heart Association 3/4, peripheral artery disease, and diabetes; and had a 1.3-fold higher estimated logistic European System for Cardiac Operative Risk Evaluation value. In-hospital mortality was independently associated with CKD stage ≥3 (up to odds ratio, 1.71; 95% confidence interval, 1.35 to 2.17; P<0.05), bleeding was independently associated with CKD stage ≥4 (up to odds ratio, 1.82; 95% confidence interval, 1.47 to 2.24; P<0.001), and AKI was independently associated with CKD stages 3 (odds ratio, 1.83; 95% confidence interval, 1.62 to 2.06) and 4 (odds ratio, 2.33; 95% confidence interval, 1.92 to 2.83 both P<0.001). The stroke risk, in contrast, was lower for patients with CKD stages 4 (odds ratio, 0.23; 95% confidence interval, 0.16 to 0.33) and 5 (odds ratio, 0.24; 95% confidence interval, 0.15 to 0.39; both P<0.001). Lengths of hospital stay were, on average, 1.2-fold longer, whereas reimbursements were, on average, only 1.03-fold higher in patients who suffered from CKD. CONCLUSIONS: This analysis illustrates for the first time on a nationwide basis the association of CKD with adverse outcomes in patients who underwent transcatheter aortic valve implantation. Thus, classification of CKD stages before transcatheter aortic valve implantation is important for appropriate risk stratification.

The Impact of Chronic Kidney Disease on Hospitalized Patients With Peripheral Arterial Disease and Critical Limb Ischemia.

Peripheral arterial disease (PAD) and chronic kidney disease (CKD) are major public health problems worldwide. Evaluations of large-scale data on morbidity, outcome, and costs in patients having PAD with CKD are essential. Cross-sectional nationwide population-based analysis of all hospitalizations for PAD during 2009 in Germany focused on the stage-related impact of CKD on morbidity, in-hospital mortality, amputations, length of hospital stay, and health-related expenditure. The total number of hospitalizations was 483 961. Of those, 132 993 (27.5%) had CKD. Chronic kidney disease caused 1.8-fold higher amputation rate ( P < .001) with a stepwise increasing rate with higher CKD stage. Chronic kidney disease doubled in-hospital mortality of patients with PAD (7.8%; n = 10 421) versus 4.0% (n = 14 174, P < .001) with a stepwise increasing risk with higher CKD stage ( P < .001). The highest in-hospital mortality occurred in patients with coprevalence of CKD stage 4 and Fontaine stage IV (16.4%, n = 1176, P < .001). Chronic kidney disease caused 15% higher costs and 21% increased length of stay compared to the whole PAD cohort. This analysis demonstrates the stage-related influence of CKD on morbidity, in-hospital mortality, amputations, length of hospital stay, and reimbursement costs of hospitalized patients with PAD.

Aging and Outcome in Patients With Peripheral Artery Disease and Critical Limb Ischemia.

BACKGROUND, OBJECTIVES, DESIGN: Aging of the population is one of the major challenges facing public health systems. The impact of aging on acute and long-term outcome of patients with peripheral artery disease (PAD) and critical limb ischemia (CLI) is currently not sufficiently clarified. This analysis consists of comprehensive, anonymized data obtained from the largest public health insurance in Germany. RESULTS: A total of 41,740 PAD patients with an index hospitalization between January 1, 2009, and December 31, 2011, and a follow-up time up to 4 years were included (40-49 years: n = 1179; 50-59 years: n = 5415; 60-69 years: n = 10,565; 70-79 years: n = 13,313; 80-89 years: n = 9714; and 90-100 years: n = 1554). Advanced age was associated with female gender (men-women ratio up to 1:3.3), less smoking, less frequent obesity, more often chronic heart failure (up to 9-fold), chronic kidney disease (up to 4-fold), fewer angiographies (up to 0.8-fold), fewer endovascular (up to 0.5-fold) and surgical revascularizations (up to 0.9-fold), higher rates of amputation (up to 2.5-fold), acute renal failure (up to 3.7-fold), in-hospital mortality (up to 12-fold), myocardial infarction (up to 2.8-fold), ischemic stroke (up to 1.5-fold), infection (up to 1.4-fold), and sepsis (up to 1.8-fold) (each P < .001). During follow-up, advanced age was a highly significant independent predictor of long-term mortality, myocardial infarction, and stroke (each P < .001). Lengths of hospital stay (up to 1.3-fold longer) and reimbursement costs (up to 1.1-fold higher) were clearly associated with advanced age (each P < .001). CONCLUSIONS: This study demonstrates the impact of aging on morbidity, in-hospital treatment, complications, and acute and long-term outcome of PAD patients.

Amputations and mortality in in-hospital treated patients with peripheral artery disease and diabetic foot syndrome.

AIMS: The prevalence of diabetes mellitus (DM) and its associated complications such as peripheral artery disease (PAD) and diabetic foot syndrome (DFS) are increasing worldwide. We aimed to determine the contemporary acute and long-term outcome of patients with PAD and DFS in Germany. METHODS: Nationwide, anonymized data of 40,335 patients hospitalized for PAD and/or DFS from the years 2009-2011 were analyzed and followed up until 2013. Patients were classified into 3 groups: DFS, PAD+DM and PAD without DM. In-hospital and long-term outcome (1156days, 95% CI 1.151-1.161) regarding major and minor amputation and mortality was assessed. Cumulative amputation-free survival and overall survival rates were calculated using Kaplan-Meier analysis. RESULTS: The proportion of DFS, PAD+DM and PAD only was 17.3%, 21.5% and 61.2%, respectively. At index-hospitalization, DFS patients had the highest amputation (31.9% vs. 11.1% vs. 6.0%), yet the lowest revascularization rate (18.2% vs. 67.8% vs. 71.6%) compared to patients with PAD only and PAD+DM (P<0.001). Cumulative 4-year survival (57.4%, 60.8% and 70.0%) and amputation-free-survival (45.4%, 74.4% and 86.5%) were lowest for DFS followed by PAD+DM and PAD only (P<0.001). CONCLUSIONS: Patients with diabetes, particularly those with DFS, have persistent high rates of limb amputation and of mortality in a real-world setting. Our data emphasize the need for further dedicated research to identify and target the underlying causes of the extraordinary poor outcome in this high risk population.

Acute and chronic anemia and short- and long-term outcome of patients with peripheral arterial disease and critical limb ischemia.

BACKGROUND: Evident data about the additive effect of "the fifth cardiovascular risk factor" (anemia) and peripheral arterial disease (PAD) focused on morbidity and outcome of patients with PAD are currently still missing. METHODS AND RESULTS: A total of 41,882 PAD patients were included. Of these, 5566 (13.3%) suffered from anemia. Patients with anemia were older (P<0.001), suffered more often from chronic kidney disease (P<0.001), coronary artery disease (P<0.001), and more severe PAD (P<0.001). However, they received significantly less endovascular revascularizations (P<0.001), had higher amputation rates (acute anemia: 3.7-fold, P<0.001; nutritional, aplastic, and anemia in chronic disease: 2.9-fold, P<0.001), higher in-hospital mortality rates (acute anemia: 6.4-fold, P<0.001; nutritional, aplastic, and anemia in chronic disease: 4.6-fold; P<0.001), had significantly higher in-hospital complications (P<0.001) compared to those without anemia. During a follow-up time up to 4years (until Dec. 31st, 2012, median 775days, 25th-75th percentiles 469-1120days) nutritional, aplastic, and anemia in chronic disease and acute anemia were high significant predictors of long-term mortality and amputation (each P<0.001). Lengths of hospital stay and reimbursement costs were higher (nutritional, aplastic, and anemia in chronic disease: 2-fold higher (P<0.001), acute anemia: 3-fold higher (P<0.001)) than in patients without anemia. CONCLUSION: This study illustrates from a large, comprehensive database the association of acute, nutritional, aplastic, and anemia in chronic disease on morbidity, in-hospital treatment and complications, short- and long term outcome, and costs of patients with PAD.

Low Rates of Revascularization and High In-Hospital Mortality in Patients With Ischemic Lower Limb Amputation: Morbidity and Mortality of Ischemic Amputation.

BACKGROUND: To assess the nationwide contemporary burden of cardiovascular risk factors, comorbidities, and in-hospital mortality in patients with lower limb amputation (LLA) due to peripheral arterial disease and critical limb ischemia (CLI) in Germany. METHODS: German nationwide data for 2005 and 2009 were analyzed regarding in-hospital rates of major and minor ischemic LLA, risk factors, comorbidities, surgical and endovascular revascularizations, and in-hospital mortality. RESULTS: In 2005, a total of 22 479 major (7.8%) and 28 262 minor (9.8%) LLAs were performed with a relative decrease of -21.8% in major LLA, yet with a relative increase of +2% in minor LLA rate in 2009. The overall revascularization rate before amputation was 46% in 2005 and 57% in 2009. In-hospital mortality for non-CLI, minor, and major amputees was 3.3%, 4.6%, and 19.8%, respectively (P < .001 for major vs minor LLA and non-CLI). CONCLUSION: The total number of ischemic LLA and amputation-related in-hospital mortality remains high in Germany in the 21st century. The poor outcome of patients with CLI might in part be due to underuse of revascularizations prior to amputation.

Long-term mortality after invasive diagnostic and endovascular revascularization in PAD patients.

BACKGROUND: The aim of this study was to assess the long-term, all-cause mortality among PAD patients hospitalized for invasive diagnostics and/or endovascular revascularization (ER) and the applied secondary prevention management. METHODS: From 2005 to 2009, at our center 582 consecutive patients underwent invasive peripheral angiography in part in combination with coronary angiography and/or ER. Patients were classified according to their Fontaine stage into 3 subgroups: Fontaine I/IIa, Fontaine IIb, and Fontaine stages III and IV (which were classified as critical limb ischemia, CLI). Demographic and clinical data were retrospectively obtained and patients followed up. RESULTS: Mean age increased with higher Fontaine stages (P=0.009). The proportion of patients with diabetes and anemia was lowest in Fontaine stage IIb and highest in CLI (each p<0.001). The cumulative all-cause mortality during follow-up was 17% in Fontaine stage I/IIa, 22% in Fontaine stage IIb and 34% in CLI, respectively (P<0.001). In multivariate cox regression models including diabetes mellitus, gender, age, creatinine and baseline hemoglobin, patients with Fontaine stage IIb had a 1.4-fold (95%CI 0.60-3.16) and those with CLI a 2.3-fold (95%CI 1.03-5.08) increased mortality compared to Fontaine stage I/IIa. At baseline, patients with CLI received significantly less beta blocker, statins, ACE or AT1 inhibitors and less anticoagulants; at follow-up only statins were significantly less often prescribed to CLI patients (all p<0.05). Univariate analyses showed that a therapy with statins (HR 0.64; CI 0.43-0.96; P=0.03) and antiplatelet/anticoagulant agents (HR 0.5; CI 0.27-0.94; P=0.03) significantly reduced mortality. CONCLUSIONS: Long-term mortality in CLI patients doubles the rate in patients with Fontaine stage I/IIa. Non-adherence to evidence-based recommendations and guidelines such as inadequate use of cardioprotective drugs might contribute to the observed high mortality rates in patients with CLI.

Outcome of patients with reduced ankle brachial index undergoing open heart surgery with cardiopulmonary bypass.

OBJECTIVES: In open heart surgery using cardiopulmonary bypass, perfusion of the lower extremities is markedly reduced which may induce critical ischaemia in patients with pre-existing peripheral artery disease. Whether these patients have an increased risk for amputation and should better undergo peripheral revascularization prior to surgery remains unclear. METHODS: From 1 January 2009 to 31 December 2010, 785 consecutive patients undergoing open heart surgery were retrospectively included. In 443 of these patients, preoperative ankle brachial index (ABI) measurements were available. The cohort was divided into four groups: (i) ABI < 0.5, (ii) ABI 0.5-0.69, (iii) ABI 0.7-0.89 or (iv) ABI ≥ 0.9. Follow-up data of 413 (93.2%) patients were analysed with regard to mortality and amputations. RESULTS: The groups differed significantly in terms of age, cardiac risk factors, performed cardiac surgery and renal function. Postoperative delayed wound healing was significantly associated with lower ABI (25.9, 15.2, 27.0 and 9.6% in Groups I-IV, respectively, P = 0.003), whereas 30-day mortality was not significantly higher in patients with lower ABI (0, 4.3, 8.1 and 3.9%, respectively, P = 0.4). Kaplan-Meier models showed a significantly lower long-term survival over 4 years in patients with reduced ABI (P = 0.001, long-rank test) while amputations occurred rarely with only one minor amputation in Group II (P = 0.023). CONCLUSIONS: Patients with reduced ABIs undergoing heart surgery showed more wound-healing disturbances, and higher long-term mortality compared with those with normal ABIs. However, no perioperative ischaemia requiring amputation occurred. Thus, reduced ABIs were not associated with increased peripheral risks in open heart surgery but ABI may be helpful in selecting the site for saphenectomy to potentially avoid delayed healing of related wounds in legs with severely impaired arterial perfusion.

Long-Term Mortality After Invasive Angiography and Endovascular Revascularization in Patients With PAD Having Chronic Kidney Disease.

Peripheral arterial disease (PAD) and chronic kidney disease (CKD) are associated with increased mortality rates. We assessed long-term outcomes of patients with PAD and CKD. Patients with PAD undergoing invasive angiography and/or endovascular revascularization between 2005 and 2010 were retrospectively classified into 5 CKD stages. A follow-up was performed and 572 patients were included, 116 patients (20%) had normal renal function, 245 were in CKD stage 2 (43%), 156 in CKD stage 3 (27%), and 55 in CKD stages 4 + 5 (10%). Diabetes mellitus, hypertension, and anemia were more frequent in higher CKD stages (P < .03). During follow-up (mean 1135 days; 95% confidence interval 1159-1259), cumulative mortality was 21% and increased with advanced CKD stages (9%, 16%, 29%, and 47%, respectively, P < .001). In multivariate Cox regression models, higher CKD stages were significantly associated with poor survival. Medication adherence for secondary prevention was significantly lower than recommended but irrespective of CKD stages. Kidney function is an independent predictor of worse long-term survival in patients with PAD. While standard medications were used less often than recommended, no differences between CKD stages were noted.

CKD and Acute and Long-Term Outcome of Patients with Peripheral Artery Disease and Critical Limb Ischemia.

BACKGROUND AND OBJECTIVES: Despite the many studies showing an association between CKD and a high risk of ischemic events and mortality, the association of CKD with peripheral arterial disease (PAD) still has not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This large cohort study assessed the association of CKD, even in the earlier stages, with morbidity, short- and long-term outcome, and costs among patients with PAD. RESULTS: We identified 41,882 patients with PAD who had an index hospitalization between January 1, 2009, and December 31, 2011. Of these, 8470 (20.2%) also had CKD (CKD stage 2: n=2158 [26%]; stage 3: n=3941 [47%]; stage 4: n=935 [11%]; stage 5: n=1436 [17%]). The ratio of women to men was 1:1.2. Compared with patients without known CKD, those with CKD had higher frequencies of coronary artery disease (1.8-fold higher; P<0.001), chronic heart failure (3.3-fold higher; P<0.001), and Rutherford PAD categories 5 and 6 (1.8-fold higher; P<0.001); underwent significantly fewer revascularizations (0.9-fold fewer; P<0.001); had a nearly two-fold higher amputation rate (P<0.001); had higher frequencies of in-hospital infections (2.1-fold higher; P<0.001), acute renal failure (2.8-fold higher; P<0.001), and sepsis (1.9-fold higher; P<0.001); had a 2.5-fold higher frequency of myocardial infarction (P<0.001); and had a nearly three-fold higher in-hospital mortality rate (P<0.001). In an adjusted multivariable Cox regression model, CKD remained a significant predictor of long-term outcome of patients with PAD during follow-up for up to 4 years (until December 31, 2012; median, 775 days; 25th-75th percentiles, 469-1120 days); the hazard ratio was 2.59 (95% confidence interval, 2.21 to 2.78; P<0.001). The projected mortality rates after 4 years were 27% in patients without known CKD and 46%, 52%, 72%, and 78% in those with CKD stages 2, 3, 4, and 5, respectively. Lengths of hospital stay and reimbursement costs were on average nearly 1.4-fold higher (P<0.001) in patients who also had CKD. CONCLUSIONS: This analysis illustrates the significant and important association of CKD with in-hospital and long-term mortality, morbidity, amputation rates, duration and costs of hospitalization, in-hospital treatment, and complications in patients with PAD.

The Preinterventional Cystatin-Creatinine-Ratio: A Prognostic Marker for Contrast Medium-Induced Acute Kidney Injury and Long-Term All-Cause Mortality.

BACKGROUND/AIMS: Contrast medium-induced acute kidney injury (CI-AKI) is an important iatrogenic complication following the injection of iodinated contrast media. The level of serum creatinine (SCr) is the currently accepted 'gold standard' to diagnose CI-AKI. Cystatin C (CyC) has been detected as a more sensitive marker for renal dysfunction. Both have their limitations. METHODS: The role of the preinterventional CyC-SCr ratio for evaluating the risk for CI-AKI and long-term all-cause mortality was retrospectively analyzed in the prospective single-center 'Dialysis-versus-Diuresis trial'. CI-AKI was defined and staged according to the Acute Kidney Injury Network classification. RESULTS: Three hundred and seventy-three patients were included (average age 67.4 ± 10.2 years, 16.4% women, 29.2% with diabetes mellitus, mean baseline glomerular filtration rate 56.3 ± 20.2 ml/min/1.73 m(2) [as estimated by Chronic Kidney Disease Epidemiology Collaboration Serum Creatinine Cystatin C equation], 5.1% ejection fraction <35%). A total of 79 patients (21.2%) developed CI-AKI after elective heart catheterization, and 65 patients (17.4%) died during follow-up. Multivariate analyses by logistic regression confirmed that the preinterventional CyC-SCr ratio is independently associated with CI-AKI (OR 9.423, 95% CI 1.494-59.436, p = 0.017). Also, the Cox regression model found a high significant association between preinterventional CyC-SCr ratio and long-term all-cause mortality (mean follow-up 649 days, hazards ratio 4.096, 95% CI 1.625-10.329, p = 0.003). CONCLUSION: The preinterventional CyC-SCr ratio is independently associated with CI-AKI and highly significant associated with long-term mortality after heart catheterization.

Atrial fibrillation is a risk marker for worse in-hospital and long-term outcome in patients with peripheral artery disease.

OBJECTIVES: To investigate the relevance of atrial fibrillation or flutter (AF) for outcome of patients who are hospitalized for peripheral artery disease (PAD) and/or critical limb ischemia (CLI). METHODS AND RESULTS: We compared baseline data, co-morbidities, procedural data as well as in-hospital and long-term outcome of 41,882 patients who were hospitalized with PAD or CLI between 2009 and 2011 according to whether they did or did not have atrial fibrillation/flutter. Follow-up was available until December 2012. Of these, 5622 patients (13.4%) had AF. AF patients were significantly older (78±9 vs. 70±11years) and had significantly more comorbidities, such as diabetes (40.8 vs. 31.1%), chronic kidney disease (40.1 vs. 19.0%), coronary artery disease (38.0 vs. 23.0%) and chronic heart failure (26.9 vs. 7.2%, each p<0.001). They had more advanced PAD as shown by higher Rutherford classes. In-hospital complications including acute renal failure, myocardial infarction, stroke sepsis and death occurred significantly more often (each p<0.001). Duration of hospital stay was significantly longer and costs were markedly higher in patients with AF (each p<0.001). Using multivariate Cox regression analyses regarding long-term outcomes, AF was an independent predictor for death (HRR 1.46; 95% CI 1.39-1.52, p<0.001), ischemic stroke (HRR 1.63; 95% CI 1.44-1.85) and amputation (HRR 1.14; 95% CI 1.07-1.21). CONCLUSION: Presence of AF in patients admitted for PAD and CLI is associated with worse in-hospital and long-term outcome than in patients without AF. This effect was independent of numerous other comorbidities and stage of vascular disease.