Atherosclerotic Vascular Events Research Articles

#1614 Fenofibrates and chronic kidney disease – Is there anything to worry about?

Abstract Background and Aims Chronic Kidney Disease (CKD) patients have increased risk of cardiovascular disease and dyslipidemia is a frequent comorbidity. Many patients are medicated with anti-lipidemic agents to reduce atherosclerotic disease and coronary vascular events. Fenofibrates are lipid-lowering agents used to treat mixed dyslipidemia and hypertriglyceridemia and are widely used by primary care physicians. Many studies described reversible increase in serum creatinine (SCr) associated with fenofibrates use, but the underlying mechanism is poorly understood. Whether hypercreatinemia is secondary to alterations in creatinine metabolism, tubular handling, or reflects a true impairment in kidney function remains unknown. This phenomenon is also fairly unknown to many primary care providers and, as a result, patients with a SCr rise while on fenofibrates are often referred to nephrology consultation. In this study, we have analyzed the effect of fenofibrate withdrawal on SCr, eGFR and hemoglobin (Hb) in patients referred to nephrology consultation for CKD or decrease of eGFR. Our aim was to understand the impact of fenofibrates withdrawal on kidney function and to look for factors that might influence the risk of fenofibrate nephrotoxicity. Methods We conducted a retrospective observational study, reviewed electronic medical records and collected data of all adult patients discontinued on fenofibrates at first nephrology consultation, between January 2022 and October 2023. Ninety patients were included, of which four were excluded due to simultaneous suspension of antihypertensive drugs. Patients were subsequently evaluated for clinical reasons from 2 to 6 months after the first appointment, with new laboratory data collected, including Hb, SCr and lipid profile. eGFR was calculated using MDRD 4 formula. Continuous variables were compared by t-test and categorical variables were compared by chi-square test. A p value of < 0.05 was considered statistically significant. All data was analyzed using Stata software. Results A total of eighty-six patients were included in this study, 65% (n=56) were male, mean age of 71.2 ± 11.4 years old; all patients were medicated with fenofibrates due to dyslipidemia and 77% (n=66) were also on statins; 94% (n=81) had hypertension, 60% (n=52) had type 2 diabetes mellitus, and 20% (n=17) had ischemic cardiopathy. Ninety-two percent (n=79) were taking renin-angiotensin system inhibitors (RASi). Nearly half the patients (49% n = 42) had stage 4 CKD and 45% (n = 39) had stage 3 CKD; Main causes of CKD were presumed diabetic kidney disease (34% n = 29) and ischemic nephropathy (15% n = 13), 30% (n = 26) of patients had undetermined etiology. Upon fibrate discontinuation, mean SCr was 2.1 ± 0.6 mg/dL and mean eGFR was 31.3 ± 10.9 mL/min/1.73 m2. Mean Hb was 12.5 ± 2.0 g/dL. After fenofibrate discontinuation, eGFR significantly improved in mean 15.2 mL/min/1.73 m2 (31.3 vs 46.5 mL/min/1.73 m2, p < 0.0001) with a mean reduction of SCr of 0.6 mg/dL (2.1 vs 1.5 mg/dL, p < 0.0001). Mean Hb increased 0.4 g/dL (12.4 vs 12.7 g/dL, p = 0.112). Mean total cholesterol was 168.4 ± 56.4 mg/dL and mean triglycerides was 234.8 ± 285.3 mg/dL. Only one patient was restarted on fenofibrate due to severe hypertriglyceridemia. Fenofibrate discontinuation effect on eGFR improvement remained statistically significant when adjusted for diabetes, hypertension, CKD etiology and RASi use. Conclusion Our study reports a consistent increase in eGFR and SCr decrease following discontinuation of fenofibrate, as other reports before. A true effect on eGFR could be supported by the Hb rise, though it did not reach statistical significance. The exact mechanism by which fenofibrates increase SCr remains to be clarified. Cardiovascular disease is the main cause of death amongst CKD population and the potential benefits of fenofibrates should not be disregarded. Our results suggest that patients started on fenofibrates should be carefully selected, specially if CKD is present, and kidney function monitoring should be considered. A drop in eGFR should prompt physicians to weigh on the strict indications for fenofibrates use.

Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients.

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = -0.27 and -0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.

Skin Perfusion Pressure Outperforms Ankle-Brachial Index in Predicting Mortality and Cardiovascular Outcomes in Hemodialysis Patients.

Skin perfusion pressure (SPP) and ankle-brachial index (ABI) are useful in screening for peripheral arterial disease in patients undergoing hemodialysis (HD). We compared the prognostic abilities of the SPP and ABI in predicting the composite outcomes of mortality and atherosclerotic vascular events. This single-center prospective cohort study enrolled 258 patients undergoing HD. The patients with SPP and ABI measurements were divided into tertiles. Log-rank tests, Cox regression analyses, and discrimination parameters were used for comparisons. Over a median follow-up period of 3.7 (1.4-5.0) years, 119 composite events were recorded. The incidence rates of composite events were 27.5, 13.3, and 9.1 per 100 person years, respectively, across the SPP tertiles (log-rank: p＜0.001), and 23.2, 13.2, and 11.6 per 100 person years across the ABI tertiles (p=0.003). With the 3rd tertiles as references, the 1st tertiles of the SPP and ABI were significantly associated with the composite outcome (adjusted hazard ratio [aHR]: 2.58, 95% confidence interval [CI]: 1.57-4.23 and aHR: 1.70, 95% CI: 1.06-2.73, respectively). Adding the tertiles of the SPP to a predictive model with established risk factors significantly improved the model performance. This improvement was larger than that of the ABI in terms of net reclassification (0.330 vs. 0.275) and integrated discrimination (0.045 vs. 0.012). Furthermore, in patients with a normal ABI, the 1st SPP tertile (＜71 mmHg) was significantly associated with the outcome (aHR, 1.97; 95% CI, 1.13-3.41) when compared to the 3rd tertile. Even patients with a normal ABI have a poor prognosis if their SPP levels are low. SPP outperformed ABI in predicting mortality and cardiovascular outcomes in HD patients.

The Association of Lung Function and Carotid Intima-Media Thickness in a Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study.

Impaired lung function is associated with atherosclerotic vascular events. Carotid intima-media thickness (cIMT) is a marker for subclinical atherosclerosis. However, few studies have examined the association between lung function and cIMT among never smokers or individuals stratified by age. We investigated the association between lung function and cIMT in the Japanese population. We conducted a cross-sectional study of 3,716 men and 8,765 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was evaluated using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) was measured using spirometry. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between lung function and cIMT and adjusted for potential confounders. A linear trend test was conducted by scoring the categories from 1 (lowest) to 4 (highest) and entering the score as a continuous term in the regression model. After adjusting for potential confounders including passive smoking, lower FEV1 and FVC were associated with higher cIMT in both men and women (P＜0.001 for linear trend). This association was confirmed even when we restricted our study to never smokers. Furthermore, even when we stratified by age, an inverse association between lung function and cIMT was confirmed in middle-aged (40-64 years) and elderly participants (65-74 years). Lower lung function was associated with higher cIMT in the Japanese population independent of age and smoking. Assessment of atherosclerosis or lung function may be required for individuals with lower lung function or atherosclerosis.

Hyperlipidemia-post-initiation-of-nilotinib-among-chronic-myeloid-leukemia-patients-in-a-tertiary-hospital-of-malaysia

Introduction: Nilotinib is effective in patients with chronic myeloid leukemia (CML), but is also associated with hyperlipidemia, which can be a risk factor for atherosclerotic vascular events. Objective: To determine the completeness in monitoring the fasting lipid profile (FLP), changes in lipid levels before and after the initiation of nilotinib, and changes in lipid levels after statin therapy. Method: This was a retrospective cohort study that included all patients with CML in the chronic or accelerated phase, who were receiving follow up under the haematology clinic of a regional referral hospital in the state of Perak, Malaysia. Patients who had been prescribed nilotinib from the beginning of January 2010 to June 2020 were included in the study, including patients who were still on treatment as well as those who, despite having their treatment discontinued during the observation period, still followed up in the clinic. The monitoring of FLP was defined as either “complete” (with both pre-initiation and post-initiation FLP available); or “incomplete” (with either one of pre-initiation or post-initiation FLP available); or “not ordered”. An LDL level of ≥ 2.6 mmol / L was considered suboptimal. Since the changes in FLP parameters were found to not be normally distributed, the data were evaluated using the Wilcoxon test, whereby a two-tailed p-value of P < 0.05 was considered statistically significant. Result: 61 patients who met the inclusion criteria were included. The FLP test was not ordered in 16 patients, incomplete in 33 patients and complete in 11 patients (18%). Patients who had completed the test displayed a significant increase in median HDL, LDL, and total cholesterol level from 1.27 to 1.46 mmol / L (p = 0.009), 2.10 to 3.30 mmol / L (p = 0.003) and 3.90 to 5.33 mmol / L (p = 0.005) respectively after the initiation of nilotinib. Statin was prescribed to 6 patients with a baseline mean LDL of 4.77 mmol / L, whereby the mean LDL was significantly reduced by 1.82 mmol / L (p = 0.003) after treatment. Conclusion: Patients experienced a significant increase in total cholesterol and LDL levels with nilotinib. Treatment with statin has elicited a significant reduction in LDL. Only a small proportion of patients received complete FLP monitoring, which warrants attention from the health authority.

Atherosclerotic cardiovascular events associated with immune checkpoint inhibitors in cancer patients.

Immune checkpoint inhibitors have demonstrated significant clinical benefits in many cancers, and the use of these drugs is rapidly expanding. Unfortunately, these agents can induce a wide range of immune-related adverse events through the activation of immune responses in non-target organs, including the cardiovascular system. Among cardiovascular immune-related adverse events, myocarditis is the most established and biologically plausible cardiac complication of immune checkpoint inhibitors therapy with immune-related pathophysiology. In contrast, atherosclerotic cardiovascular diseases, such as myocardial infarction and ischemic stroke, were not previously recognized as a part of the immune-related adverse event spectrum. However, there is now increasing preclinical and clinical evidence that suggests a possible correlation between immune checkpoint inhibitors therapy and atherosclerotic cardiovascular events, and cardiovascular disease is increasingly recognized as a toxicity of ICIs. Results from animal studies suggest that the blockade of the cytotoxic T-lymphocyte antigen 4 or programmed cell death protein 1 pathway plays a relevant role in promoting the progression of atherosclerotic lesions. Several clinical studies have reported an increased incidence of atherosclerotic vascular events after immune checkpoint inhibitor administration. Our findings suggest that clinicians should (i) recognize that immune checkpoint inhibitors can exacerbate atherosclerosis, (ii) consider the management of cardiovascular risk factors and (iii) perform periodic screening in patients receiving immune checkpoint inhibitors.

No evidence of association between habitual physical activity and ECG traits: Insights from the electronic Framingham Heart Study

No evidence of association between habitual physical activity and ECG traits: Insights from the electronic Framingham Heart Study

Acute arterial events across all vascular territories in the FOURIER trial

Abstract Background In the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trial, adding the PCSK9 inhibitor evolocumab to statin therapy reduced low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk. Although atherosclerotic coronary, cerebrovascular, and peripheral vascular events share a related pathobiology, the effect of aggressive LDL-C lowering with PCSK9 inhibition on the risk of acute arterial events across all three vascular beds is not well-described. Purpose To assess the efficacy of evolocumab on acute arterial events in all vascular territories including coronary, cerebral, and peripheral vascular beds. Methods In the FOURIER trial, patients (n=27,564) with stable atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on a statin were randomly assigned to evolocumab versus placebo and followed for a median of 2.2 years (1.8–2.5). Acute arterial events were defined as a composite of coronary (coronary heart disease [CHD] death, myocardial infarction [MI], or urgent coronary revascularization), cerebrovascular (ischemic stroke, transient ischemic attack [TIA], or urgent cerebral revascularization), or peripheral vascular (acute limb ischemia, major amputation, or urgent peripheral revascularization) events. Cox proportional-hazard models were used to assess the efficacy of evolocumab on these outcomes. Landmark and total event analyses were also done. Results Of the 2,210 first acute arterial events occurring during follow-up, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced the risk of a first acute arterial event by 19% (HR 0.81, 95% CI 0.74–0.88; P&amp;lt;0.001), with significant individual reductions in acute coronary (HR 0.83; 95% CI 0.75–0.91; P&amp;lt;0.001), acute cerebrovascular (HR 0.77; 95% CI 0.65–0.92; P=0.004), and acute peripheral vascular (HR 0.58; 95% CI 0.38–0.88; P=0.01) events (Figure, top). The magnitude of the risk reduction with evolocumab tended to increase over time, with a 16% reduction (HR 0.84; 95% CI 0.75–0.96) in the first year followed by a 24% reduction (HR 0.76; 95% CI 0.67–0.85) thereafter (Figure, bottom). There were 3,780 total acute arterial events (first plus recurrent), with a 22% reduction with evolocumab (incidence rate ratio [RR] 0.78; 95% CI 0.70–0.87). Evolocumab prevented 496 total acute arterial events as compared to 222 first events. Conclusions The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced the risk of acute arterial events across all vascular territories with a robust effect over time. These findings indicate a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The FOURIER trial was supported by Amgen.

Immune Checkpoint Inhibitors and Atherosclerotic Vascular Events in Cancer Patients.

In clinical trials and meta-analysis, atherosclerotic vascular events (AVEs) during treatment with immune-checkpoint inhibitors (ICIs) have been reported with low incidence. However, preclinical data suggest that these drugs can promote atherosclerosis inflammation and progression of atherosclerosis plaques, and there is now growing and convincing evidence from retrospective studies that ICIs increase the risk of atherosclerotic vascular events including arterial thrombosis, myocardial infarction and ischemic stroke. Prospective studies are needed to increase knowledge on long-term effect of ICIs or their combinations with other cardio-toxic drugs, but in the meantime a careful assessment and optimization of cardiovascular risk factors among patients treated with ICIs is advisable.

Low plantar skin perfusion pressure predicts long-term atherosclerotic vascular events and mortality in maintenance haemodialysis patients

Background and aimsEnd-stage renal disease is associated with an increased risk of atherosclerotic vascular disease (AVD). We investigated whether low plantar skin perfusion pressure (SPP), a useful indicator of peripheral arterial disease (PAD), predicts systemic AVD events and mortality in outpatients undergoing maintenance haemodialysis (HD). MethodsA total of 206 HD patients were enrolled and followed for 5 years. They were divided into 3 groups according to measured SPP: group 1 (G1), SPP >70 mmHg (n = 123); G2, SPP 50–70 mmHg (n = 61); and G3, SPP <50 mmHg (n = 22). ResultsDuring the follow-up period (median, 4.2 years), 56 AVD events (27.2%) and 68 deaths (33.0%) occurred. In G1, G2, and G3, the event-free survival rates were 74%, 55% and 19%, respectively, for AVD events (p < 0.01) and 73%, 54% and 26%, respectively, for mortality (p < 0.01). A Cox multivariate analysis showed that lower SPP was an independent predictor for AVD events [hazard ratio (HR) 3.12, 95% confidence interval (CI) 1.45–6.77, p < 0.01 for G3 vs. G1] and mortality (HR 3.06, 95% CI 1.57–5.98, p < 0.01 for G3 vs. G1). Furthermore, the addition of the SPP value to a model with established risk factors improved the predictability of increasing the net reclassification improvement (NRI; 0.463, p < 0.01) and integrated discrimination improvement (IDI; 0.039, p < 0.01) for AVD events. Similar results were obtained for mortality. ConclusionsLow plantar SPP can stratify risk and improve the predictability of both systemic AVD events and mortality in the maintenance HD population.

Accrual of Atherosclerotic Vascular Events in a Multicenter Inception Systemic Lupus Erythematosus Cohort

In previous studies, atherosclerotic vascular events (AVEs) were shown to occur in ~10% of patients with systemic lupus erythematosus (SLE). We undertook this study to investigate the annual occurrence and potential risk factors for AVEs in a multinational, multiethnic inception cohort of patients with SLE. A large 33-center cohort of SLE patients was followed up yearly between 1999 and 2017. AVEs were attributed to atherosclerosis based on SLE being inactive at the time of the AVE as well as typical atherosclerotic changes observed on imaging or pathology reports and/or evidence of atherosclerosis elsewhere. Analyses included descriptive statistics, rate of AVEs per 1,000 patient-years, and univariable and multivariable relative risk regression models. Of the 1,848 patients enrolled in the cohort, 1,710 had ≥1 follow-up visit after enrollment, for a total of 13,666 patient-years. Of these 1,710 patients, 3.6% had ≥1 AVEs attributed to atherosclerosis, for an event rate of 4.6 per 1,000 patient-years. In multivariable analyses, lower AVE rates were associated with antimalarial treatment (hazard ratio [HR] 0.54 [95% confidence interval (95% CI) 0.32-0.91]), while higher AVE rates were associated with any prior vascular event (HR 4.00 [95% CI 1.55-10.30]) and a body mass index of >40 kg/m2 (HR 2.74 [95% CI 1.04-7.18]). A prior AVE increased the risk of subsequent AVEs (HR 5.42 [95% CI 3.17-9.27], P < 0.001). The prevalence of AVEs and the rate of AVE accrual demonstrated in the present study is much lower than that seen in previously published data. This may be related to better control of both the disease activity and classic risk factors.

Pre-transplant diabetes predicts atherosclerotic vascular events and cardiovascular mortality in liver transplant recipients: a long-term follow-up study

Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome.Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method.Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060–29.183, p=0.049, and HR 86.097, CI 9.510–779.480, p=0.000, respectively).Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.

Impact of the new American College of Cardiology/American Heart Association definition of hypertension on atherosclerotic vascular events in systemic lupus erythematosus

BackgroundThe 2017 American College of Cardiology/American Heart Association guidelines defined hypertension at ≥130/80 mm Hg. Studies on patients with connective tissue diseases were not considered. Our aim was to assess...

Apolipoprotein B, Triglyceride-Rich Lipoproteins, and Risk of Cardiovascular Events in Persons with CKD.

Triglyceride-rich lipoproteins may contribute to the high cardiovascular risk of patients with CKD. This study evaluated associations of apo-B and markers of triglyceride-rich lipoproteins with cardiovascular events in people with CKD. Analyses were conducted in 9270 participants with CKD in the Study of Heart and Renal Protection (SHARP): 6245 not on dialysis (mean eGFR 26.5 ml/min per 1.73 m2), and 3025 on dialysis when recruited. Cox regression methods were used to evaluate associations of lipids with incident atherosclerotic and nonatherosclerotic vascular events, adjusting for demographics and clinical characteristics. Hazard ratios (HRs) were calculated per 1 SD higher level for apo-B, HDL cholesterol, LDL cholesterol, triglyceride-rich lipoprotein cholesterol (i.e., total cholesterol minus LDL cholesterol minus HDL cholesterol), non-HDL cholesterol, log triglyceride, and log ratio of triglyceride to HDL cholesterol. During a median follow-up of 4.9 years (interquartile range, 4.0-5.5 years), 1406 participants experienced at least one atherosclerotic vascular event. In multivariable adjusted models, positive associations with atherosclerotic vascular events were observed for apo-B (HR per 1 SD, 1.19; 95% confidence interval, 1.12 to 1.27), triglycerides (1.06; 1.00 to 1.13), the ratio of triglyceride to HDL cholesterol (1.10; 1.03 to 1.18), and triglyceride-rich lipoprotein cholesterol (1.14; 1.05 to 1.25). By contrast, inverse associations with nonatherosclerotic vascular events were observed for each of these lipid markers: apo-B (HR per 1 SD, 0.92; 0.85 to 0.98), triglycerides (0.86; 0.81 to 0.92), the ratio of triglyceride to HDL cholesterol (0.88; 0.82 to 0.94), and triglyceride-rich lipoprotein cholesterol (0.85; 0.77 to 0.94). Higher apo-B, triglycerides, ratio of triglyceride to HDL cholesterol, and triglyceride-rich lipoprotein cholesterol concentrations were associated with increased risk of atherosclerotic vascular events in CKD. Reducing triglyceride-rich lipoproteins using novel therapeutic agents could potentially lower the risk of atherosclerotic cardiovascular disease risk in the CKD population.

Serum folate and vitamin B12 levels are not associated with the incidence risk of atherosclerotic events over 12 years: the Korean Genome and Epidemiology Study

Atherosclerosis, a common cause of atherosclerotic vascular diseases, is associated with several risk factors including hyperhomocysteinemia, and vitamin B12 and folate are involved in homocysteine metabolism; thus, serum folate and vitamin B12 status may be associated with the risk of atherosclerotic vascular diseases mediated by homocysteine plasma concentrations. Therefore, we hypothesized that low vitamin B12 and folate levels are related to higher risks of atherosclerotic vascular disease and investigated the risk of atherosclerotic vascular events in Korean adults with low serum vitamin B12 and folate levels. This population-based cohort study followed 421 subjects aged 40-69 years for 12 years, 2003-2014. Over the follow-up period, 38 (9.0%) atherosclerotic events occurred. However, serum folate and vitamin B12 levels were not associated with the risk of stroke, coronary artery disease, or myocardial infarction or the development of peripheral arterial disease after adjustment for age, sex, smoking status, alcohol consumption, physical activity, body mass index, serum creatinine, and high-sensitivity C-reactive protein levels and a history of diabetes, hypertension, or dyslipidemia. In conclusion, the incidence of atherosclerotic vascular events in Korean adults aged 40-69 years was not associated with the serum folate or vitamin B12 status.

Use of Measures of Inflammation and Kidney Function for Prediction of Atherosclerotic Vascular Disease Events and Death in Patients With CKD: Findings From the CRIC Study

Traditional risk estimates for atherosclerotic vascular disease (ASVD) and death may not perform optimally in the setting of chronic kidney disease (CKD). We sought to determine whether the addition of measures of inflammation and kidney function to traditional estimation tools improves prediction of these events in a diverse cohort of patients with CKD. Observational cohort study. 2,399 Chronic Renal Insufficiency Cohort (CRIC) Study participants without a history of cardiovascular disease at study entry. Baseline plasma levels of biomarkers of inflammation (interleukin 1β [IL-1β], IL-1 receptor antagonist, IL-6, tumor necrosis factor α [TNF-α], transforming growth factor β, high-sensitivity C-reactive protein, fibrinogen, and serum albumin), measures of kidney function (estimated glomerular filtration rate [eGFR] and albuminuria), and the Pooled Cohort Equation probability (PCEP) estimate. Composite of ASVD events (incident myocardial infarction, peripheral arterial disease, and stroke) and death. Cox proportional hazard models adjusted for PCEP estimates, albuminuria, and eGFR. During a median follow-up of 7.3 years, 86, 61, 48, and 323 participants experienced myocardial infarction, peripheral arterial disease, stroke, or death, respectively. The 1-decile greater levels of IL-6 (adjusted HR [aHR], 1.12; 95% CI, 1.08-1.16; P<0.001), TNF-α (aHR, 1.09; 95% CI, 1.05-1.13; P<0.001), fibrinogen (aHR, 1.07; 95% CI, 1.03-1.11; P<0.001), and serum albumin (aHR, 0.96; 95% CI, 0.93-0.99; P<0.002) were independently associated with the composite ASVD-death outcome. A composite inflammation score (CIS) incorporating these 4 biomarkers was associated with a graded increase in risk for the composite outcome. The incidence of ASVD-death increased across the quintiles of risk derived from PCEP, kidney function, and CIS. The addition of eGFR, albuminuria, and CIS to PCEP improved (P=0.003) the area under the receiver operating characteristic curve for the composite outcome from 0.68 (95% CI, 0.66-0.71) to 0.73 (95% CI, 0.71-0.76). Data for cardiovascular death were not available. Biomarkers of inflammation and measures of kidney function are independently associated with incident ASVD events and death in patients with CKD. Traditional cardiovascular risk estimates could be improved by adding markers of inflammation and measures of kidney function.

Increased serum leptin levels are associated with metabolic syndrome and carotid intima media thickness in premenopausal systemic lupus erythematosus patients without clinical atherosclerotic vascular events

Aim To assess subclinical atherosclerosis and the role of inflammatory mediators, vascular endothelial cell activation markers and adipocytokines in systemic lupus erythematosus (SLE) in the presence or absence of metabolic syndrome (MetS). Methods We studied 66 premenopausal female SLE patients (20 with MetS) and 28 female healthy controls (HCs) without history of cardiovascular disease (CVD). Subclinical atherosclerosis was screened by measuring carotid intima media thickness (CIMT). Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor α (TNFα), interleukin 6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin, leptin and visfatin were measured. Results The mean age of MetS+SLE, MetS- and HC were 38.3 ± 6.7, 32.7 ± 9.3 and 29.9 ± 5.6 years, respectively. The mean disease duration, SLICC (Systemic Lupus International Collaborating Clinics damage index) and Systemic Lupus Erythematosus Disease Activity Index scores were 74.8 ± 54.9 months, 0.16 ± 0.48 and 1.18 ± 1.5, respectively, and were similar between MetS+and MetS- SLE patients. CIMT values were higher in both MetS+ and MetS- SLE patients than HCs ( p < 0.001). sICAM-1 and erythrocyte sedimentation rate levels were higher in both MetS+ and MetS- SLE patients than HCs ( p < 0.001; p = 0.002, p = 0.001). The SLE MetS+ group had higher CIMT values than SLE MetS- (right: p = 0.003; left: p = 0.025). Leptin levels and homeostatic model assessment (HOMA) scores were significantly higher in SLE MetS+ than SLE MetS- ( p = 0.018; p = 0.04). Leptin and CRP levels and body mass index, SLICC and HOMA scores were correlated with CIMT values (right: p = 0.03, p < 0.001, p < 0.001, p = 0.026 and p < 0.001, and left: p = 0.028, p = 0.03, p = 0.003, p = 0.002 and p = 0.025). Conclusions In premenopausal women with SLE without a history of CVD, CIMT values were increased and related to MetS. Leptin was increased in patients with MetS and correlated with CIMT values.

Periodontitis and Cardiovascular Risk

Atherosclerosis is a major component of the cardiovascular diseases and is centered by inflammation but its well-known predictors do not explain some of the atherosclerotic vascular disease events, generating the need to look for independent additional risk factors. Periodontitis, a chronic infection produced by oral bacteria and affecting the supporting structures of the teeth, seems to be linked with atherosclerosis and cardiovascular disease through several mechanisms, like genetic susceptibility, systemic inflammation, infection, and the molecular mimicry, the association being worsened in the presence of diabetes. The epidemiological studies revealed a modest but significant association between periodontal infections and cardiovascular disease, independent of the effect of confounding factors, but the definite effect of periodontitis and its treatment on the incidence of cardiovascular events requires further clarifications.

Abstract MP03: The AHA Life’s Simple 7 Metric is Inversely Associated with Subclinical Atherosclerosis Among South Asians: Findings From the Mediators of Atherosclerosis in South Asians Living in America Study

Objective: To examine the prevalence of the Life’s Simple 7 (LS7) metric and its associations with measures of subclinical atherosclerosis in a community-based cohort of South Asians in the U.S. Methods: We conducted a cross-sectional analysis of data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study consisting of 875 South Asians (mean age 55 y, SD=9.4, 47% women). Each LS7 component was assigned a score of 0 (poor), 1 (intermediate) and 2 (ideal) and these scores were summed to derive an overall cardiovascular health score ranging from 0 (poor adherence to AHA guidelines) to 14 (perfect adherence to AHA guidelines).Carotid intima media thickness (cIMT) and coronary artery calcium (CAC) were measures of subclinical atherosclerosis. Multivariate linear and multinomial logistic regression models were used to examine associations between the overall cardiovascular health score, modeled as tertiles, and subclinical atherosclerosis. Covariates included age, sex, insurance type, length of residency in the U.S., and acculturation. Results: The prevalence of having 0, 1, 2, 3, 4, 5, 6, and 7 ideal metrics was 1.6%, 8.3%, 20.1%, 27.9%, 21.6%, 15.8%, 4.7%, and 0%, respectively. The overall LS7 score ranged from 3-13, with median of 9; men had a lower median score compared with women (9 vs. 10, p&lt;0.05). In adjusted analyses, compared to those in the lowest tertile, those in upper tertiles had lower common cIMT (score:9-10: β= -0.06, 95% CI: -0.09 to -0.02; score:11-13: β= -0.07, 95% CI: -0.11 to -0.04), and internal cIMT (score:9-10: β= -0.14, 95% CI: -0.21 to -0.08; score:11-13: β= -0.14, 95% CI: -0.21 to -0.07). Higher LS7 scores were also associated with decreased odds of CAC. As compared to the lowest tertile of LS7, those in the highest tertile had 70% (OR=0.30, 95% CI: 0.19 to 0.47) lower odds of having CAC between 1 and 400, and 79% (OR=0.21, 95% CI: 0.08 to 0.54) lower odds of having CAC over 400. Conclusion: This is the first study to show that better cardiovascular health, as defined by the LS7 metrics, is associated with a lower burden of subclinical atherosclerosis in middle- and older-aged U.S. South Asians. Prospective follow-up of MASALA will determine whether the LS7 metric will predict incident atherosclerotic vascular disease events.

Abstract 241: Evaluation of the Parameters of the Euro Qol- 5 D Questionnaire Among Patients With Ischemic Heart Disease With Normal and Elevated BMI

Objective: The epidemic of obesity and obesity related morbidities is an important public health challenge, and is paralleled by growing incidence of metabolic syndrome which acts as a strong and significant risk factor for Ischemic heart disease and other atherosclerotic vascular events. The psychological impact of these chronic conditions can be very disturbing. In practical terms the functional effect of an illness and its therapy upon a patient, as perceived by the patient - could be estimated by introducing the quantitative approach of - Health Related Quality of Life (HRQoL). Aim: The aim of this study is to evaluate the impact of obesity on quality of life of patients with ischemic heart disease. Design and method: Questionnaire based cross sectional study was conducted among patients with established Coronary Artery Disease admitted in the Department of Cardiology in the University Hospital. 520 patients who were admitted in the Cardiology Department between 1st of January 2012 and 30th June 2014 with acute coronary syndrome or coronary angiographic or Electrocardiography evidence of ischemic heart disease were included in the study, stratified by age, sex and BMI ( normal weight 18.5 - 24.9, overweight 25 - 29.9, obese 30 and above). EuroQol - 5D (EQ-5D) was administered in the patients during their hospital stay. EQ-5D comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The height, weight and basic laboratory parameters were recorded. Results: Mean age of the participants was 65.1± 10.6 years. Male female ratio was 0.76. The distribution of patients in BMI groups was 36.8%/ 24.4%/ 38.8%. Statistically significant differences between BMI groups were seen in Usual activity (p=0.005) and self-care (p=0.044) dimensions of EQ-5D-5L with poorest outcome in the obese. We have found significantly positive correlation between BMI and usual activities (R=0.234, p=0.001) and between age and anxiety (R= 0.366 p=0.045). Mean BMI of patients with extreme problems with extreme problems with usual activities is significantly greater than those with lower intensity of problems. Patients with extreme anxiety tend to have higher mean age. Conclusion: Our study revealed that Ischemic heart disease patients with obesity had impaired QoL in terms of health, mobility, usual activity, discomfort and anxiety. Hence non-obese ischemic heart disease patients had a better sense of overall wellbeing.