High Risk Of Atherosclerotic Disease Research Articles

Factors affecting in-hospital clinical outcomes in patients with acute limb ischemia undergoing endovascular therapy or fogarty thrombectomy: a large-scale analysis based on the JROAD-DPC database

Abstract Background The etiology of acute limb ischemia (ALI) involves embolism as well as atherosclerotic thrombosis. Although endovascular therapy (EVT) or Fogarty thrombectomy (Fogarty TE) is the recommended revascularization method for ALI, treatment choice based on patient characteristics remains controversial. Purpose This study aimed to evaluate the differences in clinical outcomes between primary treatments and identify predictive factors affecting clinical outcomes in patients with ALI. Methods This retrospective study used data from the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database, from April 2012 to March 2020. We analyzed 18,701 patients with ALI and categorized them into medication and invasive treatment groups (EVT alone, Fogarty TE alone, bypass surgery alone, and hybrid treatment). The EVT-alone and Fogarty TE-alone groups were compared after propensity score matching, considering 19 clinically relevant covariates. The primary outcomes were in-hospital mortality, major amputation, and bleeding complications (anemia requiring transfusion or endoscopic hemostasis). The secondary outcomes were major adverse cardiovascular events (myocardial infarction, coronary intervention, heart failure, stroke, and cerebral hemorrhage), major amputation and/or death, hospitalization duration, and total cost during hospitalization. Results The EVT-alone group had more patients at a higher risk of atherosclerotic disease, including peripheral artery disease (PAD), chronic kidney disease (CKD), or hemodialysis. The Fogarty TE-alone group had more patients at a higher risk of embolism, including AF or AFL. After propensity score matching, in-hospital mortality (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.29–1.92, p<.0001), bleeding complications (OR: 1.28, 95% CI: 1.12–1.46, p=0.0002), and major amputation rates (OR: 1.44, 95% CI: 1.17–1.76, p=0.0004) were significantly higher in the EVT-alone group than in the Fogarty TE-alone group. Major amputation and/or death rates and total hospitalization costs were higher in the EVT-alone group than in the Fogarty TE-alone group. In interaction analyses, EVT demonstrated a favorable trend of lower risks of death and/or major amputation in patients with PAD, CKD, and diabetes mellitus (all risk factors for atherosclerotic disease), especially in those with PAD and CKD. Conclusions Fogarty TE may be the preferred primary treatment for patients with ALI, particularly those without PAD or CKD.Study flowchartForest plot analyzing interaction effect

Comparison of Clinical Outcomes in Patients with Acute Lower Limb Ischaemia Undergoing Endovascular Therapy and Open Surgical Revascularisation: A Large Scale Analysis in Japan

The recommended revascularisation methods for acute limb ischaemia (ALI), which is caused by embolism and atherosclerotic thrombosis, include endovascular therapy (EVT) and open surgical revascularisation (OSR); however, treatment choices based on patient characteristics remain controversial. This retrospective analysis from the Japanese Registry of All Cardiac and Vascular Diseases - Diagnosis Procedure Combination database (April 2012 to March 2020) evaluated differences in clinical outcomes and identified prognostic predictors in patients with ALI. This study analysed 10 977 patients with lower limb ALI. EVT was defined as catheter directed thrombolysis, percutaneous thrombectomy, or percutaneous angioplasty with balloon dilatation and or stenting. OSR was defined as Fogarty thrombectomy, bypass surgery, or thromboendarterectomy. The EVT and OSR groups were compared after propensity score matching (PSM) considering ten clinical covariates. The EVT group had more patients at higher risk of atherosclerotic disease than the OSR group. The OSR group had more patients at a higher risk of embolism, including atrial fibrillation and atrial flutter, than the EVT group. In the EVT group, 20.4% of patients underwent catheter directed thrombolysis using urokinase, the only thrombolytic agent available in Japan that is covered under insurance. After PSM, in hospital mortality (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.11 - 1.59; p = .002), major amputation rate (OR 1.43, 95% CI 1.19 - 1.72; p < .001), major amputation and or death rate (OR 1.42, 95% CI 1.24 - 1.62; p < .001), and total hospitalisation cost (1.16 vs. 0.97 million yen; p < .001) were statistically significantly higher in the EVT group than in the OSR group. In interaction analyses, peripheral artery disease (PAD) was a factor responsible for reducing OSR efficacy in terms of major amputation and or death rate (with PAD, OR 0.94, 95% CI 0.68 - 1.29; without PAD, OR 1.56, 95% CI 1.34 - 1.82; p = .004). In Japan, EVT was a less effective primary treatment for patients with ALI than OSR, except for those with PAD.

Colchicine prevents accelerated atherosclerosis in TET2-mutant clonal haematopoiesis.

Somatic mutations in the TET2 gene that lead to clonal haematopoiesis (CH) are associated with accelerated atherosclerosis development in mice and a higher risk of atherosclerotic disease in humans. Mechanistically, these observations have been linked to exacerbated vascular inflammation. This study aimed to evaluate whether colchicine, a widely available and inexpensive anti-inflammatory drug, prevents the accelerated atherosclerosis associated with TET2-mutant CH. In mice, TET2-mutant CH was modelled using bone marrow transplantations in atherosclerosis-prone Ldlr-/- mice. Haematopoietic chimeras carrying initially 10% Tet2-/- haematopoietic cells were fed a high-cholesterol diet and treated with colchicine or placebo. In humans, whole-exome sequencing data and clinical data from 37 181 participants in the Mass General Brigham Biobank and 437 236 participants in the UK Biobank were analysed to examine the potential modifying effect of colchicine prescription on the relationship between CH and myocardial infarction. Colchicine prevented accelerated atherosclerosis development in the mouse model of TET2-mutant CH, in parallel with suppression of interleukin-1β overproduction in conditions of TET2 loss of function. In humans, patients who were prescribed colchicine had attenuated associations between TET2 mutations and myocardial infarction. This interaction was not observed for other mutated genes. These results highlight the potential value of colchicine to mitigate the higher cardiovascular risk of carriers of somatic TET2 mutations in blood cells. These observations set the basis for the development of clinical trials that evaluate the efficacy of precision medicine approaches tailored to the effects of specific mutations linked to CH.

Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials

Inflammation and hyperlipidaemia jointly contribute to atherothrombotic disease. However, when people are treated with intensive statin therapy, the relative contributions of inflammation and hyperlipidaemia to the risk of future cardiovascular events might change, which has implications for the choice of adjunctive cardiovascular therapeutics. We aimed to evaluate the relative importance of high-sensitivity C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDLC) as determinants of risk for major adverse cardiovascular events, cardiovascular death, and all-cause-death among patients receiving statins. We did a collaborative analysis of patients with-or at high risk of-atherosclerotic disease, who were receiving contemporary statins and were participants in the multinational PROMINENT (NCT03071692), REDUCE-IT (NCT01492361), or STRENGTH (NCT02104817) trials. Quartiles of increasing baseline high-sensitivity CRP (a biomarker of residual inflammatory risk) and of increasing baseline LDLC (a biomarker of residual cholesterol risk) were assessed as predictors of future major adverse cardiovascular events, cardiovascular death, and all-cause death. Hazard ratios (HRs) for cardiovascular events and deaths were calculated across quartiles of high-sensitivity CRP and LDLC in analyses adjusted for age, gender, BMI, smoking status, blood pressure, previous history of cardiovascular disease, and randomised treatment group assignment. 31 245 patients were included in the analysis from the PROMINENT (n=9988), REDUCE-IT (n=8179), and STRENGTH (n=13 078) trials. The observed ranges for baseline high-sensitivity CRP and LDLC, and the relationships of each biomarker to subsequent cardiovascular event rates, were almost identical in the three trials. Residual inflammatory risk was significantly associated with incident major adverse cardiovascular events (highest high-sensitivity CRP quartile vs lowest high-sensitivity CRP quartile, adjusted HR 1·31, 95% CI 1·20-1·43; p<0·0001), cardiovascular mortality (2·68, 2·22-3·23; p<0·0001), and all-cause mortality (2·42, 2·12-2·77; p<0·0001). By contrast, the relationship of residual cholesterol risk was neutral for major adverse cardiovascular events (highest LDLC quartile vs lowest LDLC quartile, adjusted HR 1·07, 95% CI 0·98-1·17; p=0·11), and of low magnitude for cardiovascular death (1·27, 1·07-1·50; p=0·0086) and all-cause death (1·16, 1·03-1·32; p=0·025). Among patients receiving contemporary statins, inflammation assessed by high-sensitivity CRP was a stronger predictor for risk of future cardiovascular events and death than cholesterol assessed by LDLC. These data have implications for the selection of adjunctive treatments beyond statin therapy and suggest that combined use of aggressive lipid-lowering and inflammation-inhibiting therapies might be needed to further reduce atherosclerotic risk. Kowa Research Institute, Amarin, AstraZeneca.

Abstract 14822: Lipoprotein (a) is a Residual Risk Factor of Aortic Valve Calcification in Patients With High Risk of Atherosclerotic Disease

Introduction: The number of patients with aortic valve stenosis which results from aortic valve calcification (AVC), has been increasing in the elderly population. The risk factors of AVC include diabetes, dyslipidemia, and hypertension. However, control of these risk factors has not resulted in a decreased incidence of AVC. Increased Lipoprotein (LP) (a) and oxidized low-density lipoprotein (LDL), or decreased omega 3-fatty acids, are the candidates for serum biomarkers of residual risk factors. However, the most contributable risk factors for AVC has not been identified. Methods: We enrolled a total of 618 patients who underwent coronary angiography by computed tomography because of suspicion of coronary artery disease (CAD). Calcium scores were calculated using imaging software (3mensio Medical Imaging) and existence of coronary stenosis was evaluated. Patients who were suspected of having significant coronary stenosis underwent coronary angiography to confirm the existence of ischemic heart disease. Patients were evaluated for residual risk factors including Lp(a), oxidized LDL, omega 3- and 6-fatty acids, and C-reactive protein in addition to markers of conventional risk factors. Result: The calcium score in patients who received aortic valve replacement was significantly higher than that in patients who did not undergo AVR. There were no difference between the calcium scores in patients with CAD and those without CAD. Univariate analysis showed that the calcium score was associated with levels of Lp(a) (P&lt;0.01) but not with omega 3- and 6-fatty acids, oxidative LDL, hemoglobin A1c, LDL- and HDL-cholesterol, triglycerides, and C-reactive protein. Multivariate analysis showed that increased Lp(a) and age were independently correlated with the calcium score (P&lt;0.01), but sex and the existence of other conventional risk factors including hypertension, dyslipidemia, and chronic kidney disease were not. Conclusion: Serum Lp(a) is a potent risk factor for AVC in patients with high risk of atherosclerosis. Lowering Lp(a) may be a potential strategy for prevention of AVC. Intervention studies involving methods of lowering Lp(a) are needed to confirm the results.

Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia).

Familial dysbetalipoproteinemia (FDBL) is a rare inborn lipid disorder characterized by the formation of abnormal triglyceride- and cholesterol-rich lipoproteins (remnant particles). Patients with FDBL have a high risk for atherosclerotic disease. The effect of PCSK9 inhibition on lipoproteins and its subfractions has not been evaluated in FDBL. Three patients (65±7 years, 23±3 kg/m2, 2 females) with FDBL (diagnosed by isoelectrofocusing) and atherosclerosis (coronary and/or cerebro-vascular and/or peripheral arterial disease) resistant or intolerant to statin and fibrate therapy received evolocumab (140mg every 14 days). In addition to a fasting lipid profile (preparative ultracentrifugation), apoB and cholesterol concentrations were determined in 15 lipoprotein-subfractions (density gradient ultracentrifugation; d 1.006-1.21g/ml) before and after 12 weeks of evolocumab treatment. Patients with LDL-hypercholesterolemia (n = 8, 56±8 years, 31±7 kg/m2) and mixed hyperlipidemia (n = 5, 68±12 years, 30±1 kg/m2) also receiving evolocumab for 12 weeks were used for comparison. All patients tolerated PCSK9 inhibition well. PCSK9 inhibitors reduced cholesterol (29-37%), non-HDL-cholesterol (36-50%) and apoB (40-52%) in all patient groups including FDBL. In FDBL, PCSK9 inhibition reduced VLDL-cholesterol and the concentration of apoB containing lipoproteins throughout the whole density spectrum (VLDL, IDL, remnants, LDL). Lipoprotein(a) was decreased in all patient groups to a similar extent. This indicates that the dominant fraction of apoB-containing lipoproteins is reduced with PCSK9 inhibition, i.e. LDL in hypercholesterolemia and mixed hyperlipidemia, and cholesterol-rich VLDL, remnants and LDL in FDBL. PCSK9 inhibition may be a treatment option in patients with FDBL resistant or intolerant to statin and/or fibrate therapy.

Pitavastatin: Coronary Atherosclerotic Plaques Changes and Cardiovascular Prevention

Stains remain the first therapeutic approach in patients with dyslipidemia to control plasma lipids levels and cardiovascular risk. Multiple clinical trials have demonstrated the benefits of statins in reducing major cardiovascular adverse events in primary and secondary prevention. Moreover, in patients with coronary artery disease, statins decrease coronary atherosclerotic plaque volume and composition, inducing atheroma stabilization. Pitavastatin, is a new-generation lipophilic statin, indicated for the treatment of dyslipidemia and prevention of cardiovascular diseases. The purpose of this review, the first at our knowledge on this topic, is to summarize and examine the current knowledge about the effectiveness of pitavastatin in patients with coronary artery disease. The available data suggest that pitavastatin significantly, lowers the rate of adverse cardiovascular events, in patients at a high risk of atherosclerotic disease, with stable angina pectoris or with acute coronary syndrome. Moreover intravascular ultrasound have shown that pitavastatin induces favorable changes in plaque morphology, increasing the fibrous cap thickness, and decreasing both plaque and lipid volume indexes. Globally the efficacy of pitavastatin is greater or similar to other statins.

Abstract 10579: Vascular Impairment by Trimethylamine N-Oxide (TMAO) Uptake and the First Description of a TMAO Transporter in Endothelial Cells

Introduction: Trimethylamine N-oxide (TMAO) derived from dietary sources has been linked to a higher risk of atherosclerotic disease. However, the underlying mechanisms are not fully understood. Impairment of endothelial cells (ECs) by chronic inflammation or metabolic cues can lead to a loss of EC phenotype and function towards a mesenchymal cell type, a process contributing to atherosclerosis termed endothelial-to-mesenchymal transition (EndMT). Here, we investigate the potential uptake of TMAO and its impact on endothelial inflammation and EndMT. Methods &amp; Results: Using tandem mass spectrometry, we found ECs to take up TMAO in a time-dependent manner (0.5 nmol/mg within 30 min rising to 5.8 nmol/mg TMAO/total protein after 24 h). The induction of ICAM1 (+26.5-fold) and E-Selectin (+77.7-fold, both p&lt;0.05) indicated an inflammatory activation of ECs after TMAO uptake. The prolonged treatment of ECs with TMAO for 3 days induced EndMT, as indicated by increase of the mesenchymal markers Calponin 1 (+11.9-fold) and SM22 (+8.6-fold) and by a concomitant downregulation of endothelial LYVE1 (-92%, all p&lt;0.05). Functionally, the EC barrier function was significantly impaired after prolonged TMAO treatment leading to an increase in vascular permeability (+2.36-fold). The multitude of known human solute carrier proteins were screened in ECs for identification of a potential TMAO transporter. Single-cell RNA-sequencing revealed the Endothelial TMAO Transporter 1 (ETT1) to be upregulated in inflammatory-activated ECs of the myocardium. Overexpression of ETT1 resulted in a 61.7% higher intracellular TMAO concentration in ECs after 30 min of treatment. Downregulation of ETT1 by siRNA prevented TMAO-induced inflammation (-112% induction of E-Selectin and -105% induction of ICAM1) and EndMT (-315% induction of SM22 and -533% induction of Calponin 1) and restored EC barrier function (-78% induction of permeability). Conclusions: In summary, our study identifies that TMAO uptake into human ECs causes increased inflammation and induces EndMT. The TMAO-mediated impairment of EC function is prevented by down-regulation of the newly identified TMAO transporter ETT1. Our findings may help to better understand the interaction of diet and atherosclerosis.

Role of endometriosis in defining cardiovascular risk: a gender medicine approach for women’s health

The relationship between endometriosis and subclinical atherosclerosis represents an emerging topic in women’s health, as women with endometriosis are at higher risk of cardiovascular disease later in life. We investigated metabolic parameters and indirect endothelial markers related to atherosclerosis, in women suffering from stage III/IV of endometriosis compared with women without endometriosis. The study population comprised 643 women: 92 women (14.3%) with stage III/IV of endometriosis and 551 (85.7%) without endometriosis. By analyzing biohumoral parameters we observed a significant increased total cholesterol (p = 0.01), LDL-C (p = 0.01), triglycerides (p = 0.05) and homocysteinaemia (p = 0.04), lower vitamin B6 and folate (p = 0.07 and p = 0.03, respectively) values, and higher high-sensitive C reactive protein (p = 0.05) concentrations in stage III/IV in comparison to those observed in women without endometriosis. After adjustment for traditional cardiovascular risk factors, the poorer lipid profile (total cholesterol, LDL-C), as well as Lipoprotein (a), remained significantly associated with severity of endometriosis (p = 0.01 and p = 0.03, respectively). Our findings highlight the role of endometriosis as a gender-specific cardiovascular risk factor. The clinical relevance of our study lies in identifying women with stage III/IV of endometriosis at higher risk of atherosclerotic disease, who could benefit from an early cardiovascular screening to control future cardiovascular risk.

Coronary Artery Disease is More Severe in Patients with Non-Alcoholic Steatohepatitis than Fatty Liver.

Non-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of atherosclerotic disease. However, the relationships between the severity of coronary atherosclerosis and pathologic findings in patients with NAFLD remain unknown. We aimed to characterize the coronary artery lesions in patients with NAFLD using coronary computed tomography angiography (CCTA). Overall, 101 patients with liver biopsy-proven NAFLD who had chest pain or electrocardiographic abnormalities underwent CCTA. Coronary artery lesions, including coronary artery stenosis (CAS), calcium score (CACS, Agatston score), and coronary artery non-calcified plaque were assessed using multi-slice CT. Multivariate analysis showed that age, smoking status, prevalence of dyslipidemia (DLP) and non-alcoholic steatohepatitis (NASH), and stage of fibrosis were independent risk factors for CAS. Age, and the prevalence of DM and DLP, were independent risk factors for CACS, and the prevalence of NASH tended to be an independent risk factor. In addition, the prevalence of DLP and NASH were independent risk factors for non-calcified plaques. Coronary artery lesions are more common in patients with NASH than in those with non-alcoholic fatty liver, suggesting a higher risk in patients with NASH. Therefore, patients with NASH should be closely followed, with particular vigilance for coronary artery diseases.

Effect of Balloon Catheter Angioplasty Alone for Recurrent Bilateral Renal Artery Restenosis and Quick Deterioration for Hemodialysis: An Alternative for in-Stent Restenosis

Aim: Atherosclerotic renal artery stenosis is one of the main causes of secondary hypertension and results in a progressive loss of renal function. This case reports recurrent hypertensive pulmonary edema and worsening renal function successfully treated with multiple percutaneous renal interventions.&#x0D; Presentation of the Case: A 62-year-old female patient was admitted for carotid endarterectomy. She had uncontrolled blood pressure and worsened renal function. Bilateral renal artery stenosis was diagnosed and endovascular procedure plus stent was performed in both renal arteries. She was discharged with an improvement in renal function and blood pressure. Three months later, she presented a sudden onset of pulmonary hypertensive edema. Renal arteriography confirmed bilateral in-stent restenosis and a new bilateral angioplasty plus stent was fulfilled. Six months later, new worsening of dyspnea, severe renal dysfunction, and new hospitalization were indicated renal replacement therapy. Renal arteriography showed again bilateral renal artery in-stent restenosis and bilateral balloon catheter angioplasty with no stent was performed. She was discharged, with no need for hemodialysis, improved blood pressure and proposal for further discussion about surgical revascularization.&#x0D; Discussion: When severe reduction of glomerular filtration rate occurs in hypertensive patients with high risk for atherosclerotic disease, it seems prudent to examine renal arteries. Once a diagnosis is made, if blood pressure control cannot be achieved, mainly associated with progressive renal dysfunction, it is recommended restoration of renovascular supply.&#x0D; Conclusion: Percutaneous renal intervention with no-stenting in bilateral in-stent restenosis and recent onset of hemodialysis may contribute to reversion of renal dysfunction even in patients undergoing to previous interventions.

The potential for improving cardio-renal outcomes by sodium-glucose co-transporter-2 inhibition in people with chronic kidney disease: a rationale for the EMPA-KIDNEY study.

ABSTRACT Diabetes is a common cause of chronic kidney disease (CKD), but in aggregate, non-diabetic diseases account for a higher proportion of cases of CKD than diabetes in many parts of the world. Inhibition of the renin–angiotensin system reduces the risk of kidney disease progression and treatments that lower blood pressure (BP) or low-density lipoprotein cholesterol reduce cardiovascular (CV) risk in this population. Nevertheless, despite such interventions, considerable risks for kidney and CV complications remain. Recently, large placebo-controlled outcome trials have shown that sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduce the risk of CV disease (including CV death and hospitalization for heart failure) in people with type 2 diabetes who are at high risk of atherosclerotic disease, and these effects were largely independent of improvements in hyperglycaemia, BP and body weight. In the kidney, increased sodium delivery to the macula densa mediated by SGLT-2 inhibition has the potential to reduce intraglomerular pressure, which may explain why SGLT-2 inhibitors reduce albuminuria and appear to slow kidney function decline in people with diabetes. Importantly, in the trials completed to date, these benefits appeared to be maintained at lower levels of kidney function, despite attenuation of glycosuric effects, and did not appear to be dependent on ambient hyperglycaemia. There is therefore a rationale for studying the cardio-renal effects of SGLT-2 inhibition in people at risk of CV disease and hyperfiltration (i.e. those with substantially reduced nephron mass and/or albuminuria), irrespective of whether they have diabetes.

Apolipoprotein E Deficiency Increases Remnant Lipoproteins and Accelerates Progressive Atherosclerosis, But Not Xanthoma Formation, in Gene-Modified Minipigs

Deficiency of apolipoprotein E (APOE) causes familial dysbetalipoproteinemia in humans resulting in a higher risk of atherosclerotic disease. In mice, APOE deficiency results in a severe atherosclerosis phenotype, but it is unknown to what extent this is unique to mice. In this study, APOE was targeted in Yucatan minipigs. APOE-/- minipigs displayed increased plasma cholesterol and accumulation of apolipoprotein B-48-containing chylomicronremnants on low-fat diet, which was significantly accentuated upon feeding a high-fat, high-cholesterol diet. APOE-/- minipigs displayed accelerated progressive atherosclerosis but not xanthoma formation. This indicates that remnant lipoproteinemia does not induce early lesions but is atherogenic inpre-existing atherosclerosis.

CORONARY ARTERY DISEASE IN INDIVIDUALS WITH HUMAN IMMUNODEFICIENCY VIRUS COMPARED TO A SERONEGATIVE COHORT

Background: Individuals living with human immunodeficiency virus (HIV) are reported to have a higher risk for atherosclerotic disease due to both the individual and combined effects of their HIV and their antiretroviral therapy (ART). The objective of this study was to determine differences in risk

Interarm blood pressure differences predict target organ damage in type 2 diabetes.

Patients with type 2 diabetes mellitus are at high risk for atherosclerotic disease, and proper blood pressure measurement is mandatory. The authors examined the prevalence of an interarm difference (IAD) in blood pressure and its association with cardiovascular risk factors and organ damage (nephropathy, retinopathy, left ventricular hypertrophy, and vascular damage) in a large diabetic population. A total of 800 consecutive patients with type 2 diabetes mellitus were evaluated with an automated simultaneous bilateral device (men: 422 [52.8%]; mean age: 68.1±12.2years). Diabetic patients with systolic IAD ≥5 and systolic IAD ≥10mm Hg showed an increased risk of having vascular damage (adjusted odds ratios: 1.73 and 2.49, respectively) and higher pulse pressure. IAD is highly prevalent in patients with diabetes, is associated with vascular damage, even for IAD ≥5mm Hg, and should be accurately obtained to avoid underdiagnosis and undertreatment of hypertension.

PTH-338 Postoperative troponin i elevation in patients undergoing major abdominal surgery

Introduction In the UK, there is an ageing general surgical population with increasing comorbidity. Most studies evaluating postoperative elevation in troponin-I have focussed on surgery in individuals known or suspected to be at high risk of atherosclerotic disease. We aimed to determine the rates of postoperative elevation of troponin-I in patients following elective and emergency major abdominal surgery. Early identification of these patients is vital as this may allow cardiac risk modification improving long-term survival. Method One hundred patients were recruited. Demographic data was collected. Troponin-I was measured on day one and two postoperatively. If a raised troponin-I level was detected on either blood sample, an electrocardiogram was performed, the patient questioned about the presence of any symptoms and a prompt cardiology consultation was obtained. Results Fifty-five men and forty-five women were recruited (mean age 70.3, range 45–90). Thirteen of the hundred patients (13%) had postoperatively elevated troponin-I levels on day 1 or 2. Postoperative troponin-I elevation was associated with an increased mean age (P = 0.012) and with increasing CEPOD category of surgery (P = 0.009). No statistically significant difference was seen between groups for P-POSSUM scores of morbidity (P = 0.07) or mortality (P = 0.067). Conclusion Elevated postoperative troponin-I levels were identified in 13% of general surgical patients undergoing major abdominal surgery. All elevations were asymptomatic and not associated with any cardiological symptoms or ECG abnormality. Elderly patients undergoing emergency surgery are a high-risk group for perioperative cardiac damage which may contribute to the increased morbidity and risk of emergency general surgery. Disclosure of interest None Declared.

A Case of Post-partum Spontaneous Coronary Artery Dissection with Pulmonary Embolism: Survival with Thrombectomy and Stent Implant.

Spontaneous Coronary Artery Dissection (SCAD) is a rare life-threatening cause of acute coronary syndrome. It can affect young patients without atherosclerotic risk factors, particularly women in the antepartum or early post-partum period, as well as geriatric patients at high risk for atherosclerotic disease. The pathogenesis linking SCAD with pregnancy has not been fully elucidated. The few reported cases of SCAD in the setting of concomitant Pulmonary Embolism (PE) may highlight a potential mechanism in the pregnant or postpartum woman. Heretofore, cases of SCAD with the setting of pulmonary embolism have all been treated conservatively with medical therapy. We herein report a case of SCAD in the left anterior descending artery resulting in Non-ST elevation myocardial infarction and low ejection fraction associated with an acute pulmonary embolism in a young post-partum patient who was treated successfully with thrombectomy followed by stent placement. Her cardiac function returned to normal within six months with no recurrence of symptoms. To our knowledge, this is the first case of SC.

Impaired fibrous repair: a possible contributor to atherosclerotic plaque vulnerability in patients with type II diabetes.

Diabetes mellitus (DM) type II is increasing rapidly worldwide. Patients with DM II have a greater atherosclerotic burden and higher risk of developing cardiovascular complications. Inflammation has been proposed as the main cause for the high risk of atherosclerotic disease in DM II. In this study, we compared markers of inflammation and fibrous repair in plaques from subjects with and without DM II. Carotid endarterectomy specimens were obtained from 63 patients with and 131 without DM. Plaque structure, connective tissue proteins, inflammatory cells, and markers were analyzed by immunohistochemistry, ELISA, Mesoscale, and Luminex technology. Carotid plaques from diabetics had lower levels of extracellular matrix proteins, elastin, and collagen, which are critical for plaque stability. Plaques from diabetics had reduced levels of platelet-derived growth factor and matrix metalloproteinase-2, both important for tissue repair. No differences were observed in inflammatory markers in plaques from diabetic and nondiabetic patients. This study suggests that atherosclerotic plaques in subjects with DM II are more prone to rupture because of impaired repair responses rather than to increased vascular inflammation. Although this study did not have a mechanistic design, our findings suggest that targeting impaired repair responses in carotid plaques may help to increase our understanding of atherosclerotic plaque development and vulnerability in patients with DM II.

Use of a Treatment Optimization Algorithm Involving Statin-Ezetimibe Combination Aids in Achievement of Guideline-Based Low-Density Lipoprotein Targets in Patients With Dyslipidemia at High Vascular Risk Guideline-Based Undertaking to Improve Dyslipidemia Management in Canada (GUIDANC)

Background Despite the well-established benefits of strategies to reduce low-density lipoprotein cholesterol (LDL-C), many patients fail to achieve the guideline recommended targets. The objective of this study was to evaluate the impact of an enhanced 26-week algorithm-based treatment optimization strategy, involving titration of statin monotherapy and/or combination therapy with statin and ezetimibe, on achievement of guideline-based LDL-C targets in patients at high risk for atherosclerotic disease. Methods and Results In this national (172-physician) quality enhancement research initiative involving 2334 Canadian men and women (median age, 65 years) at high vascular risk who were not at the guideline-recommended LDL-C target despite statin therapy, 36.6% and 45.5% of patients achieved an LDL-C <2.0 mmol/L at visit 2 and visit 3, respectively, using the treatment optimization algorithm. The percentage of patients achieving the 2009 Canadian Cardiovascular Society (CCS)-recommended target of either LDL-C <2.0 mmol/L or a 50% or greater reduction from baseline increased from 6.8% at visit 1 to 43.3% at visit 2 and to 52.1% at visit 3. Attainment of LDL-C targets increased significantly with consecutive visits ( P < .001). Use of ezetimibe in combination with statin therapy was associated with greater target achievement. Conclusions Use of a structured treatment optimization algorithm, based on titration of statin dosages and incorporation of ezetimibe therapy when required, enabled the majority of high-risk patients to achieve guideline-recommended targets, thereby narrowing the care gap that exists in dyslipidemia management.

The experts debate: Perioperative beta-blockade for noncardiac surgery—proven safe or not?

Guidelines on perioperative management of patients undergoing noncardiac surgery recommend the use of prophylactic perioperative beta-blockers in high-risk patients who are not already taking them, and their continuance in patients on chronic beta-blockade prior to surgery. These recommendations were challenged recently by results of the Perioperative Ischemic Evaluation (POISE), a large randomized trial of extended-release metoprolol succinate started immediately before noncardiac surgery in patients at high risk for atherosclerotic disease. While metoprolol significantly reduced myocardial infarctions relative to placebo in POISE, it also was associated with significant excesses of both stroke and mortality. The merits and limitations of POISE and its applicability in light of other trials of perioperative beta-blockade are debated here by two experts in the field-Dr. Don Poldermans and Dr. P. J. Devereaux (co-principal investigator of POISE).