Risk Factor For Vascular Events Research Articles

Hypertension, C Reactive Protein and Metabolic Profile: What is the Scenario in Patients Undergoing Arteriography?

High Blood Pressure (HBP), Diabetes Mellitus (DM), Metabolic Syndrome (MS) and Cardiovascular Diseases (CVD) are among the main causes of death worldwide and HBP is one of the most common chronic health problem representing an important and modifiable risk factor for vascular events and mortality. To study the association among high sensitivity CRP levels, and the biochemical, and anthropometric profile in hypertensive and non-hypertensive patients who underwent arteriography. This research was performed at the Haemodynamic Laboratory of the University Hospital in the city of Marilia - state of São Paulo, Brazil. Ninety-five subjects who underwent arteriography were included. Anthropometric (body mass index and waist circumference) and biochemical parameters (glycaemia, total cholesterol, HDL-c, LDL-c, triglycerides, and high sensitivity C reactive protein), were evaluated. Variables pertaining to blood pressure, atherogenic indices, diagnosis of metabolic syndrome and catheterization details were collected. Statistical analysis was performed with Chi-square test, Fisher, Student t-test and ANOVA complemented by Tukey test. Our results showed that 78.95% of the patients who underwent arteriography were suffering from HBP. Hypertensive individuals had significantly higher glycaemia (124.14±45.33 mg/dL) or DM, higher values of triglycerides (195.27±74.52 mg/dL), waist circumference (98.52±12.52 cm), body mass index (29.99±1.41 kg/m2) and hs-CRP (0.53±0.44 mg/dL). Most of the hypertensive patients (93.33%) presented with MS and were related to the presence of more severe lesions in the arteries and had passed through more invasive procedures like angioplasty and surgery. Our findings indicate that blood pressure control is of paramount importance to ensure better quality of life and life expectancy as it is associated with several risk factors that increase the morbidity and mortality.

Approach to patients with essential thrombocythaemia and very high platelet counts: what is the evidence for treatment?

Treatment of essential thrombocythaemia (ET) is directed at decreasing the risk of complications of the disease, including arterial and venous thrombosis and bleeding episodes. Established risk factors for vascular events in patients with ET include advanced age (>60years) and prior history of thrombosis or haemorrhage. The role, if any, of other potential risk factors, including cardiovascular risk factors, leucocytosis, high haematocrit, and JAK2 V617F has been analysed in multiple studies. The impact of thrombocytosis on the risk of vascular events has also been investigated. Many clinicians consider an elevated platelet count to be a risk factor for thrombosis or, when extreme, bleeding and utilize this as a criterion to start cytoreductive therapy. However, the relationship between thrombocytosis and vascular events is controversial and solid evidence to support the use of cytoreductive therapy in ET patients who have no other risk factors is lacking. In this review, we discuss current treatment recommendations for patients with ET, the biology underlying vascular events and risk factors thereof. We then review the evidence on the management of patients with ET and extreme thrombocytosis.

Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation

Backgroundvon Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein...

HDL Cholesterol as a Residual Risk Factor for Vascular Events and All-Cause Mortality in Patients With Type 2 Diabetes.

To evaluate whether low HDL cholesterol (HDL-c) levels are a risk factor for cardiovascular disease and mortality in patients with type 2 diabetes and whether it remains a residual risk factor when attaining low LDL cholesterol (LDL-c) treatment goals or when LDL-c is treated with intensive lipid-lowering therapy. We performed a prospective cohort study of 1,829 patients with type 2 diabetes included in the Second Manifestations of ARTerial disease (SMART) cohort. Cox proportional hazard models were used to evaluate the risk of HDL-c on cardiovascular events and all-cause mortality. Analyses were performed in strata of LDL-c levels (<2.0, 2.0-2.5, and >2.5 mmol/L) and lipid-lowering therapy intensity and were adjusted for age, sex, BMI, smoking, alcohol, LDL-c, triglycerides, systolic blood pressure, estimated glomerular filtration rate, glucose, and HbA1c. A total of 335 new cardiovascular events and 385 deaths occurred during a median follow-up of 7.0 years (interquartile range 3.9-10.4). No relation was found between plasma HDL-c and cardiovascular events (hazard ratio [HR] 0.97, 95% CI 0.93-1.01) or all-cause mortality (HR 0.99, 95% CI 0.96-1.03). Subgroup analysis supported effect modification by plasma LDL-c levels. In patients with LDL-c levels <2.0 mmol/L, higher HDL-c was related to higher risk for all-cause mortality (HR 1.14, 95% CI 1.07-1.21). Higher HDL-c was also related to higher risk for cardiovascular events in patients with LDL-c levels <2.0 mmol/L (HR 1.10, 95% CI 1.07-1.21) in contrast to patients with LDL-c levels between 2.0 and 2.5 mmol/L (HR 0.85, 95% CI 0.75-0.95) and >2.5 mmol/L (HR 0.96, 95% CI 0.91-1.00). In high-risk patients with type 2 diabetes with LDL-c levels <2.0 mmol/L, higher HDL-c at baseline is unexpectedly related to a higher risk for cardiovascular events and all-cause mortality in contrast to high-risk patients with type 2 diabetes with LDL-c levels between 2.0 and 2.5 mmol/L.

Serum Klotho (but not haplotypes) associate with the post-myocardial infarction status of older adults

OBJECTIVES:The number of deaths from vascular diseases is incredibly high worldwide, and reliable markers for major events are still needed. The current cross-sectional study investigated the association of Klotho haplotypes and Klotho serum levels with classic risk factors and a clinical history of vascular events.METHODS:Clinical, anthropometric, biochemical and nutritional assessments were conducted with 168 older adults, complemented by genotyping (rs9536314 and rs9527025) and the detection of serum Klotho (ELISA).RESULTS:Klotho levels and haplotypes did not associate with most classic risk factors for vascular events, including markers such as C-reactive protein and homocysteine. A positive association was only found between Klotho levels and the previous occurrence of a myocardial infarction by both correlational (p=0.006) and variance analyses (p<0.001), and these associations were independent of the context.CONCLUSION:Our results suggest that serum Klotho is higher in individuals with a clinical history of myocardial infarction but not with a history of coronary artery disease or stroke. None of the Klotho haplotypes were associated with the variables investigated herein.

Thrombotic Events in Lupus Anticoagulant Positive Patients Prospectively Correlate with Clinical Risk Factors - the Vienna Lupus Anticoagulant and Thrombosis Study (LATS)

INTRODUCTIONPatients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events (TE), which in turn increase the risk of death (Gebhart J et al. Blood. 2015. 125:3477). Understanding the determinants of thrombotic risk in LA patients may pave the way towards targeted thromboprophylaxis. To date, several retrospective studies have investigated the association between anamnestic thrombosis and certain factors, such as antibodies against cardiolipin and beta2-glycoprotein I. However, robust prospective evidence is still limited. We aimed to investigate clinical and laboratory risk factors for development of TE in patients with a persistently positive LA.PATIENTS & METHODS: In this prospective, observational cohort study with a baseline biobank we followed 150 patients (median age: 41.3 years, interquartile range (IQR): 32.3-60.2, female gender: n=122 (81.3%)), who tested repeatedly positive for the LA until the development of TE, death, or censoring. The primary endpoint was the time-to-TE during the observation period, defined as a composite of arterial or venous, independently-adjudicated thrombotic complications. Ninety-eight (65.3%) of the 150 patients had a history of at least one TE event (arterial TE: n=21, venous TE: n=84, both: n=7), and 70 (46.7%) were on oral anticoagulation at baseline. Sixty-five (43.3%) patients also had IgM and/or IgG isotype antibodies against cardiolipin and beta2-glycoprotein I ("Triple positivity"). For investigation of the LA, lupus-sensitive aPTT reagents were used (aPTT-LA, Diagnostica Stago, Asnieres, France). Prospective associations were analyzed using competing risk analysis treating death-from-any-cause as the competing event. Evaluated risk factors included (1) the lupus-sensitive activated partial thromboplastin time (aPTT-LA), (2) antibodies against cardiolipin, beta2-glycoprotein I, domain 1 of beta2-glycoprotein I, prothrombin, and "triple positivity", (3) general cardiovascular risk factors (diabetes, hypertension, smoking, and hypertriglyceridemia, body mass index), and (4) AnnexinA5 resistance (A5R). RESULTSDuring a median follow-up period of 8.7 years (range: 12 days - 12.4 years), 30 TE events occurred (arterial TE: n=14, venous TE: n=16), and 20 patients died. The cumulative incidence of TE at 1, 5, and 10 years of follow-up were 4.0% (95% Confidence Interval (CI): 1.7-8.1), 12.8% (95% CI: 7.9-18.9), and 24.4% (95% CI: 16.8-32.8), respectively. In univariable analysis, a prolonged aPTT-LA (Subhazard ratio (SHR) for aPTT≥118 seconds (i.e. 75th percentile of the aPTT-LA distribution)=2.59, 95%CI: 1.27-5.31, p=0.009), diabetes (SHR=4.36, 95%CI: 1.44-13.19, p=0.009), active smoking (SHR=2.35, 95%CI: 1.16-4.77, p=0.018), and elevated triglycerides (SHR per 50mg/dL increase=1.14, 95%CI: 1.09-1.18, p<0.001) were associated with a higher risk of TE events. In multivariable analysis, the only independent predictors of a higher thrombotic risk were a prolonged aPTT-LA (adjusted SHR=2.33, 95%CI: 1.06-5.13, p=0.035), diabetes (adjusted SHR=3.79, 95%CI: 1.12-12.89, p=0.033), and active smoking (adjusted SHR=2.62, 95%CI: 1.24-5.52, p=0.012). These results prevailed after adjusting for anticoagulation at baseline. Using these three parameters allowed identification of clinical subgroups with a very high and a low risk of TE events (cumulative risk of TE after 5 years 43.3% in the high risk group and 5.6% in the low risk group, respectively, Figure 1). The other risk factors did neither in univariable nor in multivariable analysis emerge as predictors of thrombotic risk in this large cohort. CONCLUSIONDiabetes and smoking, which are established risk factors for vascular events in the general population, turned out to be relevant also in patients with the LA. Moreover, a very long lupus sensitive aPTT was as well predictive for occurrence of TE in these patients. This effect was independent of anticoagulation. Interestingly, disease defining antibodies, such as those against cardiolipin or beta2-glycoprotein I (including those against domain I) were not associated with future occurrence of TE in this LA positive patient population. These data suggest that above standard anticoagulation, interventions to control and improve metabolic status and smoking habits might influence the rates of future TE in patients with known persistent LA. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

264P Is cisplatin a risk factor for vascular events in patients with germ cell tumor

264P Is cisplatin a risk factor for vascular events in patients with germ cell tumor

Study of Risk Factors for Vascular Events in Sickle Cell Disease Traced By Neuroimaging and Trans Cranial Doppler Changes

Background : silent and overt stroke comprise10-20% of complication of sickle cell disease. There was great risk of morbidity and mortality, some time with neurocognitive dysfunctions Objective: to identify the most important risk factor for neurologic events using MRI and TCD as aid for diagnosis., Methodology: descriptive study carried out over one year period in al-zahraa hospital .thirty patients with sickle cell disease enrolled. All test done as part of follow up, which include ,serum ferritin, blood count, MRI, and TCD. Data was analyzed by using SSPS version 18. Results: of total 30 patients enrolled, only one patient found to have overt stroke, two other with silent strokeand 14 patient got abnormal TCD study. Most of CNS events found in patients with low hemoglobin (p value0.015), low red blood counts (p value 0.001), and those with high hemoglobin S concentration. Blood transfusionnoticed to be protective against stroke. Conclusion: risk of cerebral stroke was related to, severity of anemia ,high concentration of hemoglobin S Recommendations: regular monitoring of cerebral blood flow by TCD and MRI decreased morbidity andmortality, together with improvement in social, and conditional affairs of patients.

Prediction of thrombotic and hemorrhagic events during polycythemia vera or essential thrombocythemia based on leukocyte burden

BackgroundEvidences suggest an association between leukocytosis and thrombotic or hemorrhagic complication in polycythemia vera (PV) and essential thrombocythemia (ET), but clinical implication is not well known. ObjectiveTo evaluate whether leukocyte burden during follow-up is related to thrombotic or hemorrhagic events in PV and ET. Patients/MethodsWe retrospectively analyzed patients with PV or ET treated at Seoul National University Bundang Hospital, Korea. Time-weighted averages of leukocytes during the follow-up period were defined as leukocyte burden and were calculated for each patient and compared between patient subgroups. In each patient with events, leukocyte burden for the 3-month period before the event was compared with that for the entire follow-up period. ResultsIn 102 patients with PV or ET, 35 events (16 thrombotic, 19 hemorrhagic) occurred in 29 patients (median follow-up, 54months). Leukocyte burden were significantly higher in patients with events than in event-free patients (12,015×103 /μL vs. 9,567×103/μL, P=0.003). The difference was more prominent in ET patients than in PV patients, and in patients with hemorrhagic events than in those with thrombotic events. In patients with events, the leukocyte burden in the pre-event period was higher than in the entire follow-up period (16,767×103/μL vs. 12,015×103/μL, P=0.002). In all patients, leukocyte burden during entire follow-up period of 11,000×103/μL or higher was an independent risk factor for vascular events. ConclusionIn PV or ET patients, leukocyte burden during disease course is related to increased incidence of thrombotic or hemorrhagic events.

High normal albuminuria is independently associated with aortic stiffness in patients with Type 2 diabetes

High normal albuminuria is associated with higher cardiovascular risk in patients with diabetes. Increased aortic stiffness is an established risk factor of vascular events. However, the relationship between albuminuria within the normal range (0-30 mg/g) and aortic stiffness in patients with Type 2 diabetes is unknown. A total of 614 normoalbuminuric subjects with Type 2 diabetes with spot urinary albumin:creatinine ratio ≤ 30 mg/g and estimated glomerular filtration rate ≥ 60 ml min⁻¹ 1.73 m⁻² were included in the study. Aortic stiffness was assessed by carotid-femoral pulse wave velocity. Pulse wave velocity increased progressively with the increase of albumin:creatinine ratio within the normoalbuminuric range (0-30 mg/g). Only 2.6% of the subjects with an albumin:creatinine ratio in the lowest quartile (0.7-3.4 mg/g) were classified as having aortic stiffness (pulse wave velocity ≥12 m/s). In contrast, the proportion of subjects with aortic stiffness increased significantly with the increase of albumin:creatinine ratio level (11.0%, 10.4% and 13.6% in albumin:creatinine ratio quartiles 2, 3 and 4, respectively, P = 0.008). A logistic regression model revealed that the odds of having aortic stiffness were increased by 56% with a 1-SD increase of log albumin:creatinine ratio after adjustment for age, gender, duration of diabetes, HbA1c , blood pressure, HDL and LDL cholesterol, estimated glomerular filtration rate, BMI, usage of renin-angiotensin system antagonists, statins and insulin. High normal albuminuria is associated with aortic stiffness in patients with Type 2 diabetes, which may in part explain their increased cardiovascular risk.

Daytime sleepiness and risk of coronary heart disease and stroke: results from the Nurses’ Health Study II

ObjectiveThe objective of this study was to determine whether daytime sleepiness is independently associated with coronary heart disease (CHD) and stroke or whether the positive association is explained by short sleep duration, disturbed sleep, and circadian disruption, conditions that are associated with cardiometabolic risk factors for vascular events. MethodsLongitudinal analyses of data from the Nurses’ Health Study II comprising 84,003 female registered nurses aged 37–54 at baseline were conducted in 2001 with follow-up until 2009. Multivariate Cox regression was used to explore the relationship between reported daytime sleepiness and the incidence of either CHD or stroke (n=500 cases). ResultsWomen who reported daytime sleepiness almost every day, compared with rarely/never, had an elevated adjusted risk of cardiovascular disease (CVD) (hazard ratio (HR)=1.58, 95% confidence interval (CI) 1.15–2.17). Controlling for sleep variables (sleep duration, snoring, shift work, and sleep adequacy) or potential metabolic biological mediators of disrupted sleep (diabetes, hypercholesterolemia, and hypertension) appreciably attenuated the relationship (HR=1.17, 95% CI 0.84–1.65; and HR=1.34, 95% CI 0.97–1.85, respectively). Controlling for both sleep variables and metabolic risk factors eliminated an independent association (HR=1.09, 95% CI 0.77–1.53). A similar pattern was observed for CHD and stroke individually. ConclusionsDaytime sleepiness was not an independent risk factor for CVD in this cohort of women, but rather, was associated with sleep characteristics and metabolic abnormalities that are risk factors for CVD.

JAK2V617F monitoring in polycythemia vera and essential thrombocythemia: Clinical usefulness for predicting myelofibrotic transformation and thrombotic events

The JAK2V617F allele burden has been identified as a risk factor for vascular events and myelofibrotic transformation in polycythemia vera (PV) and essential thrombocythemia (ET). However, all previous studies have evaluated a single time point JAK2V617F measurement. Therefore, the frequency and the clinical significance of changes in the JAK2V617F mutant load occurring during the disease evolution remain unknown. In the present study, JAK2V617F monitoring was performed during the follow-up of 347 patients (PV = 163, ET = 184). According to their JAK2V617F evolutionary patterns, patients were stratified as stable < 50% (n = 261), stable ≥50% (n = 52), progressive increase (n = 24) and unexplained decrease (n = 10). After a 2,453 person-years follow-up, a total of 59 thrombotic events, 16 major hemorrhages, and 27 cases of myelofibrotic transformations were registered. At multivariate analyses, patients with a persistently high (≥50%) or unsteady JAK2V617F load during follow-up had an increased risk of myelofibrotic transformation (Incidence rate ratio [IRR]: 20.7, 95% CI: 6.5-65.4; P < 0.001) and a trend for a higher incidence of thrombosis (IRR: 1.7, 1-3.3; P = 0.05) than patients with a stable allele burden below 50%. In conclusion, JAK2V617F monitoring could be useful in patients with PV and ET for predicting disease's complications, especially myelofibrotic transformation.

Aspirin Resistance in Chinese Stroke Patients Increased the Rate of Recurrent Stroke and other Vascular Events

To investigate the prevalent of aspirin resistance (AR) in Chinese stroke patients and its association with recurrent stroke and other vascular events, including cardiovascular disease and death. We prospectively enrolled 634 Chinese stroke patients. Aspirin was administrated to every patient from the first day of admission. Whole blood samples were collected for platelet aggregation testing after aspirin was administered for 7-10 days. A follow-up period of 12-24 months was performed to record vascular events and hemorrhagic side effects. Aspirin resistance (AR) was detected in 129 patients (20·4%), aspirin semi-resistance (ASR) in 28 patients (4·4%) and aspirin sensitivity (AS) in 477 patients (75·2%). Logistic regression analysis found that diabetes and high levels of low density lipoprotein cholesterol (LDL) were independent risk factors for ASR and AR. During a median follow-up period of 19·4 months, the prevalence of recurrent stroke, death from all causes, myocardial infarction and vascular events overall were higher in patients with AR + ASR than in patients with AS. Cox regression analysis found that diabetes and AR were independent risk factors for vascular events. Aspirin resistance is common in Chinese patient taking antiplatelet medications. Diabetes and high LDL may induce platelet activation and thrombosis and increase the occurrence of aspirin resistance. Patients who are detected to be aspirin resistant are at a greater risk of clinically important vascular events.

Clopidogrel for Atherothrombotic Event Management in Patients with Peripheral Arterial Disease (COOPER) Study: Safety and Efficacy of Clopidogrel versus Ticlopidine in Japanese Patients.

Peripheral arterial disease (PAD) has been recognized as an independent risk factor for vascular events and contributes to an adverse prognosis. Long-term administration of clopidogrel is recommended to prevent atherothrombotic events for patients with established PAD. We investigated the benefits of clopidogrel treatment in Japanese patients with PAD. COOPER (Clopidogrel for atherOthrombOtic event management in patients with PERipheral arterial disease) was a multicenter, randomized, double-blind study to evaluate the safety and efficacy of clopidogrel (75 mg/day) compared to ticlopidine (200 mg/day) in Japanese patients with PAD. The primary endpoint was the cumulative incidence of "safety events of interest" comprising clinically significant bleeding, blood disorders, hepatic dysfunction and other serious adverse events up to 12 weeks. The other safety events and vascular events were also assessed. Patients were followed up to 52 weeks. A total of 431 patients with PAD were randomly assigned to receive either clopidogrel or ticlopidine. The cumulative incidences of "safety events of interest" at 12 weeks were 2.4% and 13.6% of patients who received clopidogrel and ticlopidine, respectively (adjusted hazard ratio, 0.161; 95% confidence interval, 0.062 to 0.416; p <0.0001). Bleeding and vascular events were similar in both groups. Clopidogrel demonstrated a favorable benefit/risk profile than ticlopidine in Japanese patients with PAD. ( ClinicalTrials.gov, Identifier: NCT00862420).

Breast Cancer, Age, and Hypertension

See related article, pp 205–211 It has been estimated that 124 cases of breast cancer occur annually per 100 000 women in the United States alone, and 23.5 of 100 000 die every year despite the advances in therapeutic options that took place over the past decades. The absolute estimates for 2011 show 230 480 new cases, with 39 520 prospected fatal cases.1 This establishes breast cancer as the most frequent malignancy and at the same time the second leading cause of cancer mortality in women. The risk of fatal outcome in women treated for breast cancer is related to cancer biology, which determines the choice of and response to therapy, as well as to comorbid conditions and age. Age plays a special role in epidemiological considerations because it is regarded to be the strongest predictor of both morbidity and mortality in both sexes, irrespective of baseline medical status. However, ways by which ageing affects prognosis in a patient diagnosed with breast cancer have not yet been fully elucidated. Hypertension is the most important modifiable risk factor for vascular events. According to the World Health Organization, it is the top leading cause of death in all societies, irrespective of level of income. Hypertension has been found to lead to accelerated senescence of the cardiovascular system, a notion confirmed by observations from hypertensive animals of an increased turnover of cells, and reduced half-life of DNA, accompanied by the presence of shorter telomere fragments in kidneys of spontaneously hypertensive rats.2 On the other hand, prevalence of hypertension increases with advancing age, with age-related changes in cardiovascular structure and function, ranging from derangement of paracrine regulation in endothelium to large arterial stiffening, establishing the pathophysiologic background for the age-dependent increase in prevalence of hypertension. The high prevalence of hypertension implies that …

Incidence Rates and Risk Factors for Vascular Events in Patients With Essential Thrombocythemia: A Multicenter Study From Korea

Essential thrombocythemia (ET) is classified as a Philadelphia chromosome-negative classic myeloproliferative neoplasm. ET is a clonal stem cell disorder that is often associated with JAK2 mutations and shares phenotypic and pathogenetic similarities with other myeloproliferative neoplasms. Hemorrhagic complications and arterial and venous thrombosis are common in patients with ET. The aim of this retrospective analysis was to assess the cumulative incidence rate and risk factors for thrombohemorrhagic events in patients with ET based on a multicenter study in Korea. A total of 239 patients with ET, from February 1995 to April 2011, were retrospectively analyzed from 4 Korean academic institutions. Data were collected through the review of medical records, and vascular events were confirmed by diagnostic procedures for establishing thrombosis and hemorrhagic complications. Of the patients (median age, 61 years; median follow-up, 51.8 months), 32 (13.4%) experienced thrombohemorrhagic complications. The 10-year cumulative incidence rate showed a 20.6% incidence of thrombohemorrhagic events. In univariate analysis, the presence of JAK2 mutations, high-risk group, previous thrombohemorrhagic events, and >60 years old were shown to have higher incidences of vascular events than any other factors. In multivariate analysis, previous thrombotic events and JAK2 mutations were independent risk factors for vascular events (hazard ratio, 2.907 [95% CI, 1.142-7.406], P =.025; and 4.146 [95% CI 1.227-14.018], P = 0.022). Previous thrombotic history and the JAK2 V617F mutation were associated with a higher 10-year cumulative incidence rate of thrombohemorrhagic events.

The Risk of Vascular and Thromboembolic Events Is Increased In Young Low-Risk Germ Cell Cancer Patients by Cisplatin Containing Chemotherapy

AbstractAbstract 5119 Introduction:It has been previously reported that both short and long term vascular and thromboembolic events (TEE) occur following cisplatin containing chemotherapy for germ-cell cancer (GCC) (Bokemeyer et al. 1998, Weijl et al. 2000, Diekmann et al. 2010). It has also been shown that patients with GCC are at higher risk of TEE than patients with non-GCC, while on cisplatin-based chemotherapy (Piketty et al. 2005). Method:We reviewed all GCC patients treated in our department from 2008 until 2010 with cisplatin-based chemotherapy and assessed the incidence of TEE. Cases were analyzed with respect to risk factors for vascular events (obesity, diabetes, nicotine abuse, prior cardiovascular disease, prior TEE), tumor characteristics (low- vs. intermediate/high-risk GCC) and age. In addition, further analysis of hemostasis laboratory tests of these patients is being performed. Result:Eight patients (8/50=16%) treated with cisplatin-containing chemotherapy developed TEE. Of these TEE, two were myocardial infarctions, four pulmonary embolisms, one patient showed thrombosis of the jugular vein and one a peripheral (femoral) arterial thrombosis. TE-risk factors included: nicotine abuse in two patients, obesity and nicotine abuse in one patient and no identifiable factors in the others (hemostasis laboratory tests are currently being performed). The median age of these 8 patients was 42 years (range 16–61). Patients were treated with PEB (cisplatin, etoposide, bleomycin) or PIV (cisplatin, ifosfamide, etoposide) initially applying continuous heparin prophylaxis with 15000IE/day (d), d1-5 only during PEB or PIV, but no low-molecular weight heparin (LMWH-) and/or aspirin (ASS-) medication for venous and arterial TEE prophylaxis thereafter. With these clinically very relevant and severe TEEs, we have adapted our PEB- and PIV protocols, adding a LMWH prophylaxis (enoxaparin 40mg d6-21 after chemotherapy). Conclusion:We observed an increased risk of major thromboembolic and vascular events with an incidence rate of 16% in GCC patients after cisplatin-containing chemotherapy. Prior studies have identified TEE-risks in GCC and with cisplatin-chemotherapy, albeit LMWH- and/or ASS-prophylaxis - without clinical trials - has not been recommended as yet. Prospective studies investigating thrombosis prophylaxis measures are currently performed in order to achieve the best standard of care for these patients. Currently an extensive hemostasis diagnostic testing from all patients with TEE is being performed. Disclosures:No relevant conflicts of interest to declare.

Why are People with &amp;#x201C;Poor Lung Function&amp;#x201D; At Increased Atherothrombotic Risk?A Critical Review with Potential Therapeutic Indications

Patients classified as having a "poor lung function" in large populations studies are at increased risk of atherothrombosis, but potential mechanisms are unclear. A large proportion of these people are affected by chronic obstructive pulmonary disease (COPD), a recognized risk factor for vascular events. Systemic inflammation is the main atherothrombotic abnormality in COPD, but hypoxia-related platelet activation, pro-coagulant status and oxidative stress may play a role. Systemic inflammation is presumably a leading mechanism of atherothrombosis also in people who have a "restrictive" spirometric dysfunction, rather than the classic obstructive pattern of COPD. Many persons with "poor lung function" are affected by diabetes and their cardiovascular risk is therefore linked to the diabetic status. Patients affected by diabetes tend to have a "restrictive" dysfunction, rather than COPD. Recent studies show that restriction at spirometry precedes the onset of diabetes, thereby representing a marker of mechanisms involved in the pre-diabetic, insulin-resistant state. This is also proved by the fact that most patients with metabolic syndrome, a pre-diabetic condition, have a restrictive ventilatory pattern at spirometry. A significant proportion of people with "poor lung function" have visceral obesity, a cardiovascular risk factor. By hampering lung expansion, visceral obesity causes a restrictive ventilatory pattern. In conclusion, the term "poor lung function" includes various chronic illnesses with different mechanisms of atherothrombosis. Research is needed for better understanding why persons with lung dysfunctions have higher cardiovascular risk, and for identifying adequate preventive strategies.

Rationale, design, and baseline data of the Japanese Primary Prevention Project (JPPP)—A randomized, open-label, controlled trial of aspirin versus no aspirin in patients with multiple risk factors for vascular events

Prevention of atherosclerotic disease has become an important public health priority in Japan due to the aging of the population and changes in diet and lifestyle factors. The Japanese Primary Prevention Project (JPPP) is a multicenter, open-label, randomized, parallel-group trial that is evaluating primary prevention with low-dose aspirin in Japanese patients aged 60 to 85 years with hypertension, dyslipidemia, or diabetes mellitus. The study cohort will be followed for a mean of 4 years. The primary end point is a composite of death from cardiovascular causes (including fatal myocardial infarction [MI], fatal stroke, and other cardiovascular death), nonfatal stroke (ischemic or hemorrhagic), and nonfatal MI. Key secondary end points include a composite of cardiovascular death, nonfatal stroke, nonfatal MI, transient ischemic attack, angina pectoris, or arteriosclerotic disease requiring surgery or intervention; each component of the primary end point; noncerebrovascular and noncardiovascular death; and extracranial hemorrhage requiring transfusion or hospitalization. End point assessment is done by a central adjudication committee that is blinded to treatment assignments. Enrollment began in March 2005 and was completed in June 2007. A total of 14,466 patients were randomly allocated to receive enteric-coated aspirin, 100 mg/d, or no aspirin. At randomization, the study cohort had a mean (SD) age of 70.6 (6.2) years; 57.8% were women, 85.0% had hypertension, 71.7% had dyslipidemia, and 33.9% had diabetes. In the study cohort, 80.4% of patients had > or =3 risk factors. The JPPP is the largest primary prevention trial of aspirin in a Japanese population that is investigating whether the benefit of aspirin in reducing risk of vascular events outweighs any bleeding risk in elderly patients with multiple risk factors.

18F-FDG PET/CT Identifies Patients at Risk for Future Vascular Events in an Otherwise Asymptomatic Cohort with Neoplastic Disease

Our objective was to evaluate the association of arterial (18)F-FDG uptake and calcifications in large arteries as detected by (18)F-FDG PET/CT with the subsequent occurrence of vascular events in otherwise asymptomatic cancer patients. Clinical follow-up information was obtained for 932 cancer patients examined with whole-body (18)F-FDG PET/CT (median follow-up time, 29 mo). Among this cohort, 279 patients had died from their oncologic disease. In 15 of 932 patients (1.6%), a vascular event, defined as ischemic stroke, myocardial infarction, or revascularization, was registered. The maximal standardized uptake value (SUV) was divided by the blood-pool SUV, yielding a target-to-background ratio (TBR) for each arterial segment. The mean TBR as well as a calcified plaque sum score per patient were calculated in the major vessels: ascending, descending, and abdominal aorta, aortic arch, as well as iliac and carotid arteries. A significant correlation was observed between mean TBR and calcified plaque sum (P < 0.001). Although calcified plaque sum significantly correlated with all conventional risk factors for vascular events, mean TBR correlated only with age, the male sex, and hypertension. The Cox regression hazard model identified a mean TBR >or= 1.7 and a calcified plaque sum >or= 15 as independent predictors for the occurrence of a vascular event. Patients with both mean TBR and calcified plaque sum above these thresholds were identified as having the highest risk for a future vascular event. However, a mean TBR >or= 1.7 had greater prognostic value than did a calcified plaque sum >or= 15. In a large cohort of cancer patients, increased (18)F-FDG uptake in major arteries emerged as the strongest predictor of a subsequent vascular event. Concomitant severe vascular calcifications seemed to impart a particularly high risk. Given the small event rate in the present study, larger, prospective trials of patients without cancer are required to substantiate these promising results.