Incidence, Risk Factors, and Prognosis of Cholesterol Crystal Embolism Because of Percutaneous Coronary Intervention.

Cholesterol crystal embolism (CCE) is a rare but serious complication of percutaneous coronary intervention (PCI). However, its incidence, risk factors, and prognosis in the contemporary era are not well known. We included 23,184 patients who underwent PCI in our institution between January 2000 and December 2019 in this study. The diagnosis of CCE was made histologically or by the combination of cutaneous signs and specific blood test results. In patients with CCE, we evaluated the incidence, risk factors, and prognosis. A total of 88 patients (0.38%) were diagnosed with CCE. The incidence of CCE seemed to decline through the investigated 20 years. Positive predictors of CCE were age ≥70 years (68% vs 59%, p = 0.012), aortic aneurysm (23% vs 7.2% p <0.001), and a femoral approach (71% vs 45%, p <0.001), whereas a negative predictor of CCE was the use of an inner sheath (63% vs 77%, p <0.001). The rate of 1-year mortality and the requirement for chronic hemodialysis within 1 year after PCI in patients with CCE were 10% and 11%, respectively. The use of an inner sheath and a nonfemoral approach was associated with a lower incidence of CCE. In conclusion, because the prognosis of patients with CCE is still poor, preprocedural identification of high-risk patients and selection of low-risk procedures could be important for preventing CCE.

Proportion and risk factors of cholesterol crystal embolization after cardiovascular procedures: a retrospective national database study.

Cholesterol crystal embolization (CCE) is a rare, mainly iatrogenic condition. The proportion of CCE after cardiovascular procedures has not been fully elucidated. The purpose of this study was to determine the proportion of CCE diagnosed after cardiovascular procedures and to identify risk factors for CCE occurrence. Data on patients aged older than 40 years who underwent cardiovascular procedures between July 2010 and March 2017 were extracted from the Japanese Diagnosis Procedure Combination database. Inpatients diagnosed with CCE within 1 year after procedures in the same hospital were identified. Logistic regression analysis was performed to identify factors associated with the occurrence of CCE. There were 962 patients with CCE in 2,190,300 patients who underwent cardiovascular procedures. The overall proportion of CCE after cardiovascular procedures was 4.4 per 10,000 patients (95% confidence interval 4.1-4.7). The overall in-hospital mortality among patients with CCE was 11% (107/962). Older age, male sex, smoking, heart failure, peripheral vascular disease, cerebrovascular disease, renal insufficiency, diabetes mellitus, hypertension, and aortic aneurism and dissection were significantly associated with the higher occurrence of CCE. Compared with cardioangiography, several procedures were significantly associated with higher occurrence of CCE, including intra-aortic balloon pumping, percutaneous transluminal angioplasty of the renal artery, and transcatheter aortic valve implantation or balloon aortic valvuloplasty. CCE is rare but remains a severe complication of cardiovascular procedures. Atherosclerotic risk factors and certain cardiovascular procedures were associated with CCE.

[Update on cholesterol crystal embolism]. / État des lieux de la maladie des emboles de cholestérol.

Cholesterol crystal embolism is a systemic pathology associated with diffuse atherosclerosis. Pathophysiology corresponds to tissue necro-inflammation secondary to arteriolar occlusion associated with microembolism from atherosclerotic plaques of large diameter arteries. The clinical presentation is heterogeneous and polymorphic. Multiple organs may be the targets, but preferential damage is skin, kidneys and digestive system. It is a serious pathology, underdiagnosed, with a poor prognosis. The risk factors for developing the disease remain the same risk factors as atheroma. The factors favouring migration of microembolism remain mainly vascular interventional procedures; easy to diagnose, they oppose spontaneous embolic migrations or secondary to the introduction of antithrombotic treatment, whose diagnosis is more difficult and the prognosis more severe. The diagnosis of the disease remains mostly a diagnosis of elimination and often refers to a bundle of clinical, biological, morphological and histologic arguments. The treatment is poorly codified and the subject of few publications. It will favour both symptomatic treatment (and mainly that of pain) and complications (high blood pressure, renal insufficiency). The aetiological support remains less consensual. The treatment of atherosclerotic plaques consists, of course, in the correction of classical cardiovascular risk factors, the introduction of a statin. It will be discussed in the implementation of surgery or angioplasty to exclude potentially responsible atherosclerotic lesions. Eviction of antithrombotic therapy should be considered in terms of the benefit-risk balance, but often in favour of maintaining it. Finally, other treatments may be proposed in a case-by-case basis, such as oral or intravenous corticosteroid therapy, colchicine or LDL aphaeresis.

Better With Ultrasound: Arterial Line Placement.

Arterial catheterization is frequently performed in ICUs to facilitate hemodynamic monitoring and frequent blood sampling. Overall, arterial catheterization has high success and low complication rates, but in patients who are critically ill, the incidence of failure is higher because of hypotension, peripheral edema, and obesity. Ultrasound guidance significantly increases the likelihood of successful cannulation and decreases complications compared with traditional landmark-based techniques. Multiple ultrasound techniques for radial and femoral arterial catheter insertion have been described; this paper presents an approach for incorporating these tools into bedside practice, including illustrative figures and narrated video presentations to demonstrate the techniques described.

[Kidney disease care for the elderly]. / Spécificités des néphropathies du sujet âgé.

In our aging population, kidney disease management needs to take into account the frailty of the elderly. Standardized geriatric assessments can be proposed to help clinicians apprehend this dimension in their daily practice. These tools allow to better identify frail patients and offer them more personalized and harmless treatments. This article aims to focus on the kidney diseases commonly observed in elderly patients and analyze their specific nephrogeriatric care modalities. It should be noticed that all known kidney diseases can be also observed in the elderly, most often with a quite similar clinical presentation. This review is thus focused on the diseases most frequently and most specifically observed in elderly patients (except for monoclonal gammopathy associated nephropathies, out of the scope of this work), as well as the peculiarities of old age nephrological care.

Cholesterol-embolization syndrome: current perspectives.

Cholesterol-embolization syndrome (CES) is a multisystemic disease with various clinical manifestations. CES is caused by embolization of cholesterol crystals (CCs) from atherosclerotic plaques located in the major arteries, and is induced mostly iatrogenically by interventional and surgical procedures; however, it may also occur spontaneously. Embolized CCs lead to both ischemic and inflammatory damage to the target organ. Therefore, anti-inflammatory agents, such as corticosteroids and cyclophosphamide, have been investigated as treatment for CES in several studies, with conflicting results. Recent research has revealed that CES is actually a kind of autoinflammatory disease in which inflammasome pathways, such as NLRP3 and IL1, are induced by CCs. These recent findings may have clinical implications such that colchicine and IL1 inhibitors, namely canakinumab, may be beneficial in the early stages of CES.

Cholesterol embolization syndrome: An under-recognized entity in cardiovascular interventions.

Cholesterol embolization syndrome (CES) is a multi-systemic disease caused by embolization of atherosclerotic plaque contents from proximal large-caliber artery to distal small to medium arteries, occurring spontaneously or more commonly after vascular intervention. This report is a comprehensive review of the reported cases of CES found in our literature search. We discuss the risk factors, clinical manifestations, management, and prognosis of CES. The major predisposing factors for CES include older age, male sex, atherosclerotic cardiovascular risk factors, anticoagulation, and femoral access route. The composite incidence of atheroembolic renal disease was 92% and mortality 63%. Our review highlights the importance to recognize this disease entity for the cardiologist and nephrologist.

Association between absolute blood eosinophil count and CKD stages among cardiac patients.

Elevated eosinophil count was shown to be associated with the development of cholesterol embolization syndrome, a potentially life-threatening condition, after catheter-based procedures. We investigated the association between stages of chronic kidney disease (CKD) and the absolute eosinophil count (AEC) among cardiac patients. CKD stages were determined solely on the estimated glomerular filtration rate or requirement for hemodialysis. Eosinophilia is defined as an eosinophil count exceeding 500/µL. A total of 1022 patients were enrolled in the current study, and eosinophil counts (/µL) in the first through fourth eosinophil count quartiles were <88, 88 to 154, 155 to <238, and 238 ≤, respectively, and 29 patients (2.8 %) had eosinophilia. Correlation coefficient between the AEC and age was -0.188 (P = 0.001) in women and -0.042 (n.s.) in men (by Spearman's correlation test). Patients with higher CKD stages had a higher prevalence of the highest AEC quartile or eosinophilia. Logistic regression analysis using severe renal dysfunction (i.e., CKD stage 4 or 5) as the dependent variable, the highest AEC quartile had a significant positive association with an odds ratio of 1.99 (95 % confidence interval, 1.20-3.31, P < 0.01) after adjustment for sex, age, systolic blood pressure, and total white blood cell count. Similarly, after adjustment for the same variables, eosinophilia was associated with severe renal dysfunction with an odds ratio of 2.60 (95 % confidence interval, 1.08-6.26, P < 0.05). Eosinophil count was positively associated with higher CKD stages among cardiology patients, some fraction of which might be related to subclinical cholesterol embolization.

Atheroembolic disease--a frequently missed diagnosis: results of a 12-year matched-pair autopsy study.

Diagnosis of atheroembolic disease (AD) is challenging, because no specific test is available and AD often masquerades as other clinical conditions. We conducted the current study to investigate the relative frequency of autopsy-proven AD over time, to describe its clinical presentation, and to identify risk factors for AD. We screened 2066 autopsy reports from 1995 to 2006 for AD. For each AD case, a control patient without AD was matched for age, sex, and autopsy year. Diagnostic and therapeutic interventions (surgery, catheter interventions, and drug treatment) in the last 6 months before death, as well as clinical and laboratory parameters during the last hospitalization, were retrieved from electronic charts. We identified 51 patients with AD. Among these only 6 (12%) had been diagnosed clinically. The organs most often affected were kidney (71%), spleen (37%), and lower gastrointestinal tract (22%). The relative AD frequency decreased over time from 3.5 to 0.5 per 100 autopsies, whereas the frequency of clinically suspected and biopsy-proven AD remained constant. Among clinical signs, skin lesions such as livedo reticularis and blue toe (33% vs. 14%; p = 0.04) were significantly increased in AD patients compared with the matched controls. We also observed a trend for higher incidence of eosinophilia and proteinuria in AD patients. Vascular interventions within 6 months before death were highly associated with AD (55% vs. 29%; p = 0.01), and in a multivariable analysis this remained the only significant risk factor for AD. Thus, the diagnosis of AD is frequently missed. Vascular interventions represent the most important risk factor for AD and should be performed restrictively in high-risk patients.

[Atheroembolic renal disease: analysis of clinical and therapeutic factors that influence its progression]. / Enfermedad renal ateroembólica: un análisis de los factores clínicos y terapéuticos que influyen en su evolución.

Cholesterol embolism is a disease caused by distal showering of cholesterol crystal released from disintegration of arterial atheromatous plaques. It may occur spontaneously or more often after invasive vascular procedures or thrombolytic/anticoagulant agents. Forty five cases were diagnosed between 1989 and 2005 in three Spanish hospitals. The diagnosis was confirmed by histology or diagnostic ophthalmoscopic findings. The majority were male (93.3%), elder (55.5% were older than 70 years), smoker (91.1%), had hypertension (95.6%), with high prevalence of cardiovascular risk factors. At the time of diagnosis all patients presented acute renal failure. Mean serum creatinine at diagnosis was 4.3+/- 2.4 mg/dl. The acute renal failure was accompanied with eosinophilia (64.4%) and cutanous lesions (57.7%). 20% of cases occur spontaneously and 46.7% after endovascular manipulation (coronary angiography/arteriography) and only 8% after changes in anticoagulant treatment. After a follow-up of 12 +/- 16.3 months the 55.6% of patients need chronic dialysis, 64.4% died, 8 of them after the beginning of dialysis. Nine patients recovered renal function, with a mean creatinine of 3 +/- 1.7 mg/dl at the end of follow-up. The cardiovascular comorbididy and the clinical severity of the embolism don t have impact in the renal or patient survival. Renal survival (Kaplan-Mier) were better in spontaneous than in iatrogenic cholesterol embolism. Fifteen of 45 patients were treated with steroids. In treated patients we observed a high incidence of death (73.3% versus 60%) and fewer recovery of renal function (13.3% versus 23%), without statistical significance. The mean time to dialysis was shorter in treatment patients (p= 0.017). Statins treatment was not associated with outcome (renal or individual). In summary, atheroembolic renal disease represents an acute renal failure with special characteristics. Renal and individual outcome is poor, but some patients have spontaneous recovery of renal function. Renal survival was significantly better in spontaneous disease. We don t observe beneficial effect of steroid treatment.

Combined assessment of carotid vulnerable plaque, renal insufficiency, eosinophilia, and hs-CRP for predicting risky aortic plaque of cholesterol crystal embolism.

BACKGROUND: Cholesterol crystal embolism (CCE) is a serious complication of vascular procedures and based on the clinical features of patients with CCE, the aim of the present study was to establish screening criteria for aortic complex plaques (ACP) at high-risk of CCE. METHODS AND RESULTS: For the first study, 10 patients diagnosed as having CCE were recruited. They had prior multiple atherosclerotic disease and a high proportion of complex plaques of the carotid artery and aorta. Elevated levels of high-sensitivity C-reactive protein (hs-CRP), eosinophilia, and renal insufficiency were already recognized before CCE diagnosis. The second study prospectively enrolled 102 patients. ACP is related to CCE and predictive criteria of ACP were established. Among 19 patients with ACP, 2 presented with CCE. Multivariate analysis revealed carotid complex plaque, eosinophilia and multiple atherosclerotic risk factors as independent predictors of ACP. The criteria including these factors (multiple atherosclerotic risk factors, carotid complex plaque, hs-CRP > or =0.2 mg/dl, eGFR < or =60 ml . min(-1) . 1.73 m(-2), eosinophil count > or =400 /microl) could detect patients with ACP with 95% sensitivity, 94% specificity, and 79% positive predictive value. CONCLUSIONS: Multiple atherosclerotic risk factors, elevated hs-CRP, renal insufficiency, eosinophilia before CCE diagnosis and carotid complex plaques were features of patients with CCE. Diagnostic criteria including these characteristics effectively predict ACP patients at high-risk of CCE. (Circ J 2010; 74: 51 - 58).

Impact of blood pressure levels on different types of stroke: the Hisayama study.

OBJECTIVE: Clinical uncertainty remains whether the blood pressure classification and risk stratifications recommended by the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009) are useful in predicting the risks of stroke and its subtypes in the general Japanese population. METHODS: A total of 1621 stroke-free residents of a Japanese community aged at least 40 years were followed up for 32 years. Outcomes were total and cause-specific stroke (lacunar infarction, atherothrombotic infarction, cardioembolic infarction, cerebral haemorrhage and subarachnoid haemorrhage). Incidence was calculated by the pooling of repeated observations method. RESULTS: The age-adjusted incidence of total stroke rose progressively with higher blood pressure levels in both sexes (both P for trend <0.0001). A similar pattern was observed for lacunar infarction in both sexes and for cerebral haemorrhage in men: the differences were significant between optimal blood pressure and grades 1-3 hypertension (all P < 0.05). The age-adjusted incidence of atherothrombotic infarction in either sex and that of cardioembolic infarction and subarachnoid haemorrhage in women significantly increased in grade 3 hypertension (all P < 0.05). These associations remained substantially unchanged even after adjustment for other risk factors. In regard to risk stratification, the age-adjusted incidence of stroke significantly increased with the level of risk in both sexes. CONCLUSION: Our findings suggest that the blood pressure classification and risk stratifications recommended by the JSH 2009 guidelines are useful in predicting the risk of stroke in a general Japanese population, but the magnitude and patterns of the impact of blood pressure categories are different among stroke subtypes.

Renal function, atherothrombosis extent, and outcomes in high-risk patients.

BACKGROUND: Although prior data showed an association between chronic kidney disease (CKD) and atherothrombotic events, little is known about the risk profile and specific outcomes of atherothrombotic outpatients with CKD. METHODS: More than 69,000 outpatients at risk of atherothrombotic events were enrolled in the REACH Registry. Creatinine clearance (CrCl) was available for 51,208 patients divided into 4 groups: normal (CrCl > or =90 mL/min, n = 13,949), mild (60-89 mL/min, n = 19,474), moderate (30-59 mL/min, n = 15,883), and severe CKD (CrCl <30 mL/min, n = 1902). Baseline characteristics, number of arterial beds overtly affected, medications, overall mortality, cardiovascular death, myocardial infarction, stroke, congestive heart failure, peripheral arterial events, and bleeding events were assessed according to renal function. RESULTS: The number of arterial beds affected increased with severity of CKD. However, patients with severe CKD were less likely to receive medications of proven benefit. Severe CKD was an independent correlate of all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, peripheral arterial revascularization, or amputation. CONCLUSION: One third of outpatients at risk for atherothrombotic events have moderate to severe CKD. They are less likely to receive beneficial therapies despite a higher atherothrombotic burden and worse outcomes.

[Smoking and stroke]. / Rôle du tabagisme dans la pathologie vasculaire cérébrale.

Up to one quarter of all strokes are directly attributable to cigarette smoking, that percentage can get up to 50% for young adults admitted for an cryptogenic ischemic stroke. Cigarette smoking increases the relative risk of ischemic stroke about two-fold, three-fold for subarachnoid haemorrhage. Current smoking is not clearly identified as a risk factor for intra-cerebral haemorrhage. The risk is consistent for all subtypes of stroke according aetiology and is strongest for ischemic stroke caused by arterial atherothromboembolism. The risk is dependent upon the amount of cigarettes smoked and passive smoking is a substantial risk of stroke. The relative risk is maximal in middle age, declining with advancing years. The toxicity is higher among female smokers, especially when they have several risk factors such as oral contraceptiveS and migraine with aura. Whereas it is well known that the effectiveness of cigarette withdrawal reduces the risk of new vascular event, two thirds of young patients continue to smoke.

Case Report: Atheroembolic renal disease in a 72-year-old patient through coronary intervention after myocardial infarction.

Cholesterol embolization or atheroembolic renal disease (AERD) is an often underdiagnosed issue in patients featuring a prevalent risk profile. It is a multisystemic disease with progressive renal insufficiency due to foreign body reaction of cholesterol crystals flushed into a small vessel system of the kidneys from the arteriosclerotic plaques. The most common setting in which it occurs is iatrogenic after vascular catheterization and less frequent spontaneously. Typical clinical symptoms are delayed impairment of renal function, cutaneous manifestations such as livedo reticularis or purple toes with persistingly palpable arterial pulse, myalgia, systemic symptoms such as weight loss and fever, and abdominal and neurological symptoms. Diagnosis is generally made by clinical appearance, risk profile, and interval of time from intervention; a definitive diagnosis can only be made by renal biopsy. Even though the exact incidence is not known because most patients do not undergo biopsy due to older age, comorbidity, and other explanations for loss of renal function, it is estimated to be 4% after vascular intervention. Patient and renal outcome is dependent on comorbidity, risk profile, and preexisting chronic kidney disease (CKD). About 30% of patients are estimated to require maintenance dialysis and these patients have a high risk of death within 24 months after the first renal replacement therapy. Prognosis is also influenced by severity. The case reported is a 72-year-old male patient with preexisting CKD stage 3 undergoing percutaneous coronary intervention after myocardial infarction and consecutive AERD with typical clinical appearance 6 weeks after the event.

Validity of the ATP III diagnostic criteria for the metabolic syndrome in an elderly Italian Caucasian population: the Italian Longitudinal Study on Aging.

The metabolic syndrome (MetS) is represented by the co-occurrence of multiple metabolic and physiologic risk factors for both type 2 diabetes mellitus and atherosclerotic cardiovascular diseases. In spite of its high frequency and association with morbidity and mortality in the adult population, very little is known about its magnitude in the elderly and about the validity of the diagnostic criteria commonly used. The objective of this paper is to assess the prevalence rate of MetS and the validity of the Adult Treatment Panel III (ATP III) diagnostic criteria in an elderly Caucasian cohort, considering data from the Italian Longitudinal Study on Aging (ILSA), a population-based study with a sample of 5632 individuals aged 65-84 years at baseline (1992). Logistic regression models and ROC curve were used to test the validity of the cut off levels proposed. The prevalence of MetS was 31.5% in men, and 59.8% in women. The cut off levels suggested for both men and women by the ATP III panel indicated a significant association with the MetS for all components. Actually, the ROC analysis would suggest lower levels for glycaemia (106 mg/dl) in men, and higher levels for blood pressure in both men and women (145/95 and 135/90, respectively). Concluding, MetS is very common in the aged Caucasians and the diagnostic criteria proposed by the ATP III panel seem to be appropriate in older individuals. Small adjustments in the cut off levels could be suggested for glycaemia (men) and in blood pressure (men and women).

Cholesterol embolization in renal allografts: a clinicopathologic study of 12 cases.

Cholesterol embolization (CE) in renal allografts is a rare occurrence, the natural history and prognostic significance of which is poorly characterized. We studied the clinicopathologic features and outcome of the largest known series of CE in renal allografts and combined our cases with those in the literature. We identified renal allograft biopsies with CE from 1997 to September 2004 at University of Pittsburgh Medical Center (UPMC). All pathology material related to such biopsies were examined and correlated with clinical information to determine the most probable CE source. Among 5435 RAB, 19 from 12 cadaveric transplant recipients comprising 7 males and 5 females (median age=63 y) had CE. Donors consisted of 9 males and 2 females (median age=47 y). One donor's age and sex was unknown. The most probable CE source was recipient in 9 cases and donor in 3 cases. Five had acute renal failure without acute cellular rejection and 2 had CE-specific failed allografts. Of 19 RAB, the most frequent coexisting diagnosis was chronic allograft nephropathy (63%). The median follow-up time was 661 days. Combining UPMC and non-UPMC cases (n=37) revealed a statistically significant loss of grafts with donor-derived (P value=0.00459) and early CE (P value=0.00938). In renal allografts, CE most often correlated with recipient and donor atherosclerosis. It may present with acute renal failure, but usually not acute graft loss. Graft failure is significantly associated with donor-derived and early CE. Although its prognosis may be poor in the setting of primary nonfunction, prolonged graft survival may be seen.