scholarly journals Clonal Hematopoiesis Is Associated with Risk of Cardiovascular Disease in Individuals with Human Immunodeficiency Virus

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3277-3277
Author(s):  
Brian Wiley ◽  
Kristin Erlandson ◽  
Katherine Tassiopoulos ◽  
Yizhe Song ◽  
Rachel Presti ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Research Funding ◽  
Case Control ◽  
Reverse Transcriptase Inhibitors ◽  
Blood Draw ◽  
Clonal Hematopoiesis ◽  
Increased Risk ◽  
Living With Hiv

Abstract Introduction An estimated 1.2 million individuals in the United States are living with HIV (www.hiv.gov). Thanks to modern antiretroviral therapies (ART), the life expectancies of individuals living with HIV now approach those of people without HIV (Marcus 2020). But with this, an increase in the proportion of deaths due to non-infectious causes has occurred including, predominately, cardiovascular disease (CVD). Multiple studies have shown that HIV infection is an independent risk factor for cardiovascular disease. This increased risk is multifactorial due to an increased prevalence of traditional CVD risk factors and HIV-specific risk factors including ART, chronic inflammation and immune activation (Hsue 2010). Clonal Hematopoiesis, characterized by the expansion of blood cells stemming from a mutant hematopoietic stem/progenitor cell (HSPCs) is an emerging risk factor for cardiovascular disease. Mechanistically, this is thought to be driven, at least in part, by CH-induced proinflammatory circulating leukocytes (Jaiswal 2017, Bick 2020). Recent data suggest that inflammatory states may also promote the expansion of DNMT3A and TET2 CH mutant HSPCs suggesting a potential feedback loop (Zheng 2019, King 2019). CH has been recently reported to be increased among individuals living with HIV (Dharan 2021). Whether CH is a risk factor for HIV-associated CVD is not known. Given evidence of an increased prevalence of CH among those with HIV, we hypothesized that CH would predict risk of CVD. Methods We performed a nested case-control study drawn from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) observational study which was a long-term study of individuals with newly diagnosed HIV receiving ART (N=4,371). Cases who developed a cardiovascular event were matched to controls with no event based on age at blood draw and sex. Peripheral blood mononuclear cells (PMBCs) were isolated from the blood draw closest to the time of CVD event or time of censoring, for cases and controls respectively. Extracted DNA was subjected to whole exome sequencing (WES) at a median depth of 500x. We also included WES data from 267 children sequenced using the same platform as a technical panel of normal (PON). Mutation calling was performed using Mutect2, VarDict and Varscan2. We retained variants that met the following criteria: 1) passed by at least two callers 2) showed statistically significant higher variant allele fraction (VAF) compared to our PON 3) had VAF between 2-35% 4) at least 6 reads supporting the variant 5) passed additional post-calling filters for germline variants and sequencing artifacts 6) were annotated as a putative driver of CH based on previously defined criteria. Results Over 13 years of follow-up we observed 83 cardiovascular events: 4 cases of ASC, 14 of stroke, 25 of cerebrovascular accident, 37 of myocardial infarction, 2 of peripheral artery disease, and 1 heart failure. The mean age of our participants was 51.6 years, 81% were male, 35% percent were African-American, 17% were Hispanic and 2% were Asian. Among 161 participants (83 cases and 78 controls) we observed at least one CH mutation in 14% of participants (18% of cases and 10% of controls). The median VAF was 3.5% with 23 individuals harboring a median of 1 mutation (range 1-2). In a conditional logistic regression model adjusted for race, Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score and stratified by case-control matched pairs, CH was significantly associated with CVD (OR=3.70, 95% CI 1.03-13.23 p=0.045). Because of the possible confounding effects of classes of ART therapy on the CH-CVD association, we explored whether the prevalence of CH differed based on prior exposure to ART sub-class(es). We did not observe differences in the frequency of CH among individuals with prior exposure to different ART regimens (Non-Nucleoside Reverse Transcriptase Inhibitors 14%, Nucleoside reverse transcriptase inhibitors 17%, Protease inhibitors 20%, Integrase inhibitors 18%) Conclusions Among individuals with HIV, CH is associated with a nearly four-fold increased risk of CVD. These findings highlight the relevance of CH to HIV-associated CVD and provide support for interventions targeting potential CH-induced pro-inflammatory states among patients with HIV. Disclosures Erlandson: Gilead Sciences: Consultancy, Research Funding; Viiv Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy. Bolton: bristol myers squibb: Research Funding.

Peripheral Blood Cytopenia and Subsequent Risk of Cardiovascular Disease and Mortality

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5002-5002
Author(s):  
Radhika Gangaraju ◽  
Insu Koh ◽  
Marguerite R. Irvin ◽  
Leslie A. Lange ◽  
Damon E. Houghton ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Mortality Risk ◽  
Peripheral Blood ◽  
Cvd Risk ◽  
Clonal Hematopoiesis ◽  
Chd Risk ◽  
Increased Risk ◽  
Cvd Mortality

INTRODUCTION: African-Americans (blacks) have higher risk of stroke and coronary heart disease (CHD) - collectively referred to here as cardiovascular disease (CVD), than Caucasian-Americans (whites). Though partly explained by traditional cardiovascular risk factors, half of the excess risk in blacks is not explained by known risk factors. Recent data suggest increased risk of CVD and mortality in individuals with clonal hematopoiesis, which often presents as cytopenia. Using peripheral blood cytopenia as a marker of clonal hematopoiesis, we examined the association between cytopenia and risk of CVD and mortality in blacks and whites. METHODS: The REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study enrolled 30,239 US black and white adults between 2003 and 2007 (41% black). Socio-demographics and medical history were obtained by telephone interview, and laboratory studies (including complete blood count [CBC]) and physical exam from an in-home visit at baseline. Participants or their proxies were contacted every 6 months to ascertain CVD events, hospitalizations or deaths, and medical records were reviewed to confirm these events. Cytopenia was defined using thresholds in Table 1 as presence of 2 or more of the following: i) hemoglobin in age-, sex-, and race-specific lowest 5th percentile; ii) white cell count in race-specific lowest 5th percentile; iii) platelet count in lowest 5th percentile, and iv) macrocytosis (MCV >98fL). Participants with pre-baseline history of stroke (for analyses including stroke or CVD mortality) or CHD (for analyses including CHD or CVD mortality) and those with missing CBC were excluded. Cox proportional hazards models were used to calculate hazard ratios (HRs) of incident CVD and mortality associated with cytopenia. Models adjusted for socio-demographics (Model 1), Framingham stroke or CHD risk factors (Model 2), and estimated glomerular filtration rate and C-reactive protein (Model 3) were used. Differences in the association of cytopenia with outcomes by race were tested using cross-product interaction terms, using a p of <0.1 for interaction. RESULTS: The study included 19,544 participants who were followed for a median of ~9 years. There were 798 (4.3% of those at risk) incident stroke cases and 727 (4.3%) incident CHD cases; 1033 (5.3%) died of CVD, and 3933 (20.1%) died of all-causes. Cytopenia was present in 378 (1.9%) participants, ranging from 0.9% to 3.5% in blacks, 1.4 to 3.9% in whites, 1.6 to 3.9% in men, and 0.9 to 1.8% in women, with increasing prevalence by age. There was no association between cytopenia and stroke or CHD risk in any model. However, cytopenia was associated with increased risk of all-cause mortality (HR=1.73, 95%CI: 1.34-2.22), and CVD mortality (HR=1.56, 95% CI: 1.11-2.19) in the extended risk factor Model 3 and also in CVD risk factor adjusted model (Model 2), with little evidence of confounding (Table 2). While the race by cytopenia interaction term was not significant in any model for incident CHD or mortality, the interaction for cytopenia by race for stroke was statistically significant (p-interaction=0.08) in Model 2. The HR of stroke for cytopenia in blacks was 0.86 (95%CI: 0.46-1.61), and for whites was 1.96 (95%CI: 1.0-3.82). CONCLUSION: In this large biracial cohort, cytopenia was associated with increased all-cause and CVD mortality. Cytopenia was a race-specific risk factor for stroke affecting white Americans but not black Americans. With growing knowledge on the role of clonal hematopoiesis in CVD risk and mortality, further work is needed to determine if our phenotype of cytopenia is accurate in classifying clonal hematopoiesis and for determining the mortality risk. Given these findings, assessing clonal hematopoiesis and outcomes related to clonal hematopoiesis in diverse populations is critical to understanding the interactions between somatic mutations in hematopoietic cells and CVD/mortality risk. Disclosures Safford: Amgen: Research Funding.

scholarly journals Association between Risk Factors for Vascular Dementia and Adiponectin

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Juhyun Song ◽  
Won Taek Lee ◽  
Kyung Ah Park ◽  
Jong Eun Lee
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Signal Transduction ◽  
Vascular Dementia ◽  
Case Control ◽  
Case Control Studies ◽  
Insulin Signal Transduction ◽  
Increased Risk ◽  
The Brain

Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia.

scholarly journals Lifestyle Risk Factors and All-Cause and Cardiovascular Disease Mortality: Data from the Korean Longitudinal Study of Aging

2019 ◽  
Vol 16 (17) ◽  
pp. 3040 ◽  
Author(s):  
Inhwan Lee ◽  
Shinuk Kim ◽  
Hyunsik Kang
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Physical Inactivity ◽  
Mortality Data ◽  
Lifestyle Risk Factors ◽  
Disease Mortality ◽  
Increased Risk ◽  
Lifestyle Risk ◽  
Cvd Mortality

This study examined the association between lifestyle risk factors and all-cause and cardiovascular disease (CVD) mortality in 9945 Korea adults (56% women) aged 45 years and older. Smoking, heavy alcohol intake, underweight or obesity, physical inactivity, and unintentional weight loss (UWL) were included as risk factors. During 9.6 ± 2.0 years of follow-up, there were a total of 1530 cases of death from all causes, of which 365 cases were from CVD. Compared to a zero risk factor (hazard ratio, HR = 1), the crude HR of all-cause mortality was 1.864 (95% CI, 1.509–2.303) for one risk factor, 2.487 (95% confidence interval, CI, 2.013–3.072) for two risk factors, and 3.524 (95% CI, 2.803–4.432) for three or more risk factors. Compared to a zero risk factor (HR = 1), the crude HR of CVD mortality was 2.566 (95% CI, 1.550–4.250) for one risk factor, 3.655 (95% CI, 2.211–6.043) for two risk factor, and 5.416 (95% CI, 3.185–9.208) for three or more risk factors. The HRs for all-cause and CVD mortality remained significant even after adjustments for measured covariates. The current findings showed that five lifestyle risk factors, including smoking, at-risk alcohol consumption, underweight/obesity, physical inactivity, and UWL, were significantly associated with an increased risk of all-cause and CVD mortality in Korean adults.

scholarly journals Psoríase e Doença Cardiovascular

2013 ◽  
Vol 26 (5) ◽  
pp. 601
Author(s):  
Tiago Torres ◽  
Rita Sales ◽  
Carlos Vasconcelos ◽  
Manuela Selores
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Independent Risk Factor ◽  
Cardiovascular Comorbidities ◽  
Increased Risk ◽  
Systemic Inflammatory Disease ◽  
Obesity Hypertension

Psoriasis is a common, chronic and systemic inflammatory disease associated with several comorbidities, such as obesity, hypertension, diabetes, dyslipidaemia and metabolic syndrome, but also with an increased risk of cardiovascular disease, like myocardial infarction or stroke. The chronic inflammatory nature of psoriasis has been suggested to be a contributing and potentially independent risk factor for the development of cardiovascular comorbidities and precocious atherosclerosis. Aiming at alerting clinicians to the need of screening and monitoring cardiovascular diseases and its risk factors in psoriatic patients, this review will focus on the range of cardiometabolic comorbidities and increased risk of cardiovascular disease associated with psoriasis.

scholarly journals Thrombotic Events with NovoSeven® RT in Approved Indications Are Rare (0.2%) and Associated with Older Age (>= 65 y), Cardiovascular Disease, and Concomitant Use of aPCCs

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1203-1203
Author(s):  
Madhvi Rajpurkar ◽  
Stacy E. Croteau ◽  
Lisa N Boggio ◽  
David L Cooper
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Research Funding ◽  
Temporal Relationship ◽  
Factor Vii ◽  
Concomitant Treatment ◽  
Postmarketing Surveillance ◽  
Increased Risk ◽  
Fvii Deficiency

Abstract Introduction: Recombinant activated factor VII (NovoSeven®RT, Novo Nordisk A/S) is approved for treatment of bleeding and perioperative management in congenital hemophilia with inhibitors (CHwI), acquired hemophilia (AH), congenital factor VII (FVII) deficiency, and Glanzmann thrombasthenia (GT) with refractoriness to platelets. Serious thrombotic events (TEs) have been reported in clinical trials and postmarketing surveillance; however, the incidence of this risk (rate of thrombosis) is considered to be low within labeled indications. While many general risk factors are noted in the prescribing information (PI), the association of reported TEs with certain risk factors noted in the PI has not been established. Methods: A retrospective safety assessment of clinical trials and registries, used to support licensure and postmarketing surveillance, was performed from which the rate of thrombosis could be calculated in the 4 indicated disorders. Further, all postmarketing TE case reports in the Novo Nordisk safety database (including from registries, spontaneous reports, and the literature) were assessed to identify any of the risk factors listed in the PI and the temporal relationship to NovoSeven®RT use (defined as within 48 h given 2- to 3- hour half-life). Results: In clinical trials and registries used to support licensure and in postmarketing surveillance, overall rate of thrombosis was 0.17% of 12,288 bleeding and surgical episodes. There were 21 TEs identified (12 CHwI, 5 AH, 3 FVII deficiency, 1 GT). The specific risk by indication (Table 1) was 0.11% for CHwI (11,121 episodes), 0.19% for GT (518 episodes), 0.82% for FVII deficiency (367 episodes) and 1.77% for AH (282 episodes). Analysis of all postmarketing databases (Table 2) revealed 213 TEs (88 CHwI, 61 AH, 53 FVII deficiency, 11 GT). The majority were reported spontaneously (141), with fewer reported in the literature (47) or solicited in registries or investigator-sponsored studies (25). Of 213 TE cases, temporal relationship was assessed as plausible in 188 (88%) if NovoSeven®RT use was reported within 48 hours prior to TE or timing unknown; timing was more than 48 hours in 25 (12%) of cases. Overall, the most common associated risk factor was "elderly," defined in the PI as age ≥65 years (29%), and was particularly common in patients with AH and TE (67%). Another common factor was concomitant use of activated prothrombin complex concentrates (aPCC), identified in 18% of all TEs and 34% of TEs in CHwI. Broadly defined cardiovascular disease (including arrhythmias) was noted in 18% of all TEs (36% AH, 15% FVII deficiency, 9% CHwI) and was much more common than specific note of atherosclerotic disease (2%). Other risk factors listed in the PI were uncommon and, in some cases, never identified in TE reports (eg, postoperative immobilization, sepsis, liver disease, disseminated intravascular coagulation, neonates, pregnancy, postpartum hemorrhage, crush injury). Conclusions: Data show that the rate of TEs within licensed indications is low (0.17%), as was originally described in the US PI from 1999-2009. It has remained stable over time during postapproval surveillance in multiple US and global registries, with active surveillance for safety information across the 4 approved indications. In postmarketing safety report assessments of patients with CHwI receiving concomitant treatment with aPCCs, older patients, particularly those with AH who are receiving other hemostatic agents, and patients with a history of cardiac and vascular disease may have an increased risk of developing TE. Disclosures Rajpurkar: HEMA biologics: Honoraria; Bristol Myers Squibb: Research Funding; Shire: Honoraria; Pfizer: Honoraria, Research Funding; Novonordisk: Honoraria. Croteau:CSL-Behring: Consultancy; Catalyst Biosciences: Consultancy; Genetech: Consultancy, Research Funding; Novo Nordisk: Consultancy; Octapharma: Consultancy, Honoraria, Research Funding; Pfizer: Research Funding; Spark Therapeutics: Research Funding; Tremeau Pharmaceuticals: Consultancy; Bioveritiv: Consultancy; Biomarin: Consultancy; Bayer: Consultancy; Baxalta/Shire: Consultancy, Research Funding. Boggio:Novo Nordisk: Honoraria. Cooper:Novo Nordisk: Employment.

scholarly journals Maternal cardiovascular disease risk factors as predictors of preterm birth in California: a case–control study

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e034145
Author(s):  
Anne B. Rohlfing ◽  
Gregory Nah ◽  
Kelli K. Ryckman ◽  
Brittney D. Snyder ◽  
Deborah Kasarek ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Preterm Birth ◽  
Disease Risk ◽  
Case Control ◽  
Chronic Hypertension ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk ◽  
Early Preterm Birth

ObjectiveTo determine whether maternal cardiovascular disease (CVD) risk factors predict preterm birth.DesignCase control.SettingCalifornia hospitals.Participants868 mothers with linked demographic information and biospecimens who delivered singleton births from July 2009 to December 2010.MethodsLogistic regression analysis was employed to calculate odds ratios for the associations between maternal CVD risk factors before and during pregnancy (including diabetes, hypertensive disorders and cholesterol levels) and preterm birth outcomes.Primary outcomePreterm delivery status.ResultsAdjusting for the other maternal CVD risk factors of interest, all categories of hypertension led to increased odds of preterm birth, with the strongest magnitude observed in the pre-eclampsia group (adjusted OR (aOR), 13.49; 95% CI 6.01 to 30.27 for preterm birth; aOR, 10.62; 95% CI 4.58 to 24.60 for late preterm birth; aOR, 17.98; 95% CI 7.55 to 42.82 for early preterm birth) and chronic hypertension alone for early preterm birth (aOR, 4.58; 95% CI 1.40 to 15.05). Diabetes (types 1 and 2 and gestational) was also associated with threefold increased risk for preterm birth (aOR, 3.06; 95% CI 1.12 to 8.41). A significant and linear dose response was found between total and low-density lipoprotein (LDL) cholesterol and aORs for late and early preterm birth, with increasing cholesterol values associated with increased risk (likelihood χ2 differences of 8.422 and 8.019 for total cholesterol for late and early, and 9.169 and 10.896 for LDL for late and early, respectively). Receiver operating characteristic curves using these risk factors to predict late and early preterm birth produced C statistics of 0.601 and 0.686.ConclusionTraditional CVD risk factors are significantly associated with an increased risk of preterm birth; these findings reinforce the clinical importance of integrating obstetric and cardiovascular risk assessment across the healthcare continuum in women.

A Canadian Multicenter Case-Control Study of the Risk of Venous Thrombosis in Car and Airplane Travelers.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 491-491
Author(s):  
Lucie Opatrny ◽  
Stanley Shapiro ◽  
Marie-Jose Miron ◽  
Yury Monczak ◽  
Susan R. Kahn
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Media Coverage ◽  
Independent Risk Factor ◽  
Case Control Study ◽  
Case Control ◽  
Male Body ◽  
Increased Risk ◽  
Car Travel ◽  
Control Study

Abstract Background: The potential association between venous thromboembolism (VTE) and travel, particularly air travel (“economy class syndrome”), has been the subject of extensive media coverage. While it is biologically plausible that prolonged travel is an independent risk factor for VTE, epidemiological data to date are conflicting, and confounders have rarely been accounted for. Aim: To determine whether there is a greater risk of exposure to travel in patients with confirmed DVT compared with patients in whom DVT is ruled out. To examine the influence of confounding variables on the relation between DVT and travel. Methods: This was a Canadian multi-center case control study. Consecutive patients presenting to the vascular laboratory with clinically suspected DVT were eligible to participate. Cases were patients with objectively confirmed DVT on venous ultrasound; controls were patients in whom DVT was ruled out. Detailed recent travel history, medications and clinical characteristics were obtained via standardized, interviewer-administered questionnaires. Genetic testing for Factor V Leiden and Prothrombin gene mutations was performed. Unconditional multivariate logistic regression analyses with adjustment for confounders and testing for interactions were performed to examine the relation between DVT and (1) any travel, and (2) duration of travel. Plane and car travel were also analyzed separately. Results: There were 359 cases and 359 controls. Mean age among cases was 56 years and 50% were male. Among controls, mean age was 64 years and 35% were male. Body mass index, smoking status and patient location (inpatient vs. out-patient) were comparable between the two groups. The crude and adjusted odds ratio (OR) for exposure to travel in cases was 1.15 (95% confidence interval (CI): 0.78, 1.69) and 1.44 (95%CI: 0.86, 2.40), respectively. Travel of ≥ 12 hours’ duration was associated with a higher OR (adjusted OR 2.92, 95%CI: 0.54, 15.73) than shorter travel durations (adjusted OR 1.29; 95%CI: 0.62, 2.66). Analyzing plane and car travel separately showed that the adjusted OR for plane travel was 2.28 (95%CI: 0.94, 5.50) but for car travel was 1.00 (95%CI: 0.54, 1.83). Increasing durations of plane travel, but not car travel, resulted in higher ORs. For plane travel ≥ 12 hours, the crude OR was 8.22 (95%CI: 1.02, 66.05) and the adjusted OR was 7.10 (95% CI: 0.70, 72.35). No statistical interactions were detected between travel and thrombophilia, hormonal therapy, or clinical VTE risk factors. Interpretation: This is the largest case control study to date of the relation between DVT and travel that takes into account concurrent DVT risk factors. Plane travel but not car travel appears to be a mild independent risk factor for DVT. However, flights of 12 hours or longer were associated with a 7-fold increased risk of DVT. Our findings may have future implications regarding the use of thromboprophylaxis during long-haul travel.

scholarly journals Non-traditional Cardiovascular Risk Factors in Chronic Kidney Disease (CKD) and Haemodialysis Dependent patients - A Case Control Study

1970 ◽  
Vol 11 (2) ◽  
pp. 108-114 ◽  
Author(s):  
Ratan Das Gupta ◽  
Muhibur Rahman ◽  
HAM Nazmul Ahasan ◽  
Md Billal Alam ◽  
Md Titu Miah ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Case Control Study ◽  
Case Control ◽  
Factor Vii ◽  
Endstage Renal Disease ◽  
Increased Risk ◽  
Traditional Risk Factors ◽  
Dependent Patient ◽  
Control Study

Background: Compared with general population mortality rates are 10-20 times higher among patients with endstage renal disease, with 50% of this excess burden being attributable to cardiovascular disease. This excess risk is notentirely explained by elevation of traditional risk factors. Elevation of several Non-traditional risk factors associatedwith an increased risk for cardiovascular disease in CKD and haemodialysis dependent patients.Methods: It was a case control study which included total 96 subjects, 48 were non-dialysis CKD patients, 22Heamodialysis dependent patients and 26 healthy controls. Non-traditional risk factors homocysteine, fibrinogen,CRP, factor VII activity and haemoglobin estimated and compared with normal control population.Results: The study revealed that homocysteine , fibrinogen , CRP, factor VII significantly increased and haemoglobinwas significantly low in both non-dialysis CKD and haemodialysis dependent patients in comparison to control group.Mean homocysteine 15.38, 27.30, 23.76 μmol/L in control, non-dialysis CKD and haemodialysis dependent patientrespectively. Fibrinogen in control , non-dialysis CKD and haemodialysis dependent patient were 180.25 , 264.10 ,259.59 mg/dl respectively. CRP level in control, non-dialysis CKD and haemodialysis dependent patient were 3.90,52.59, 17.31 mg/L respectively. Factor VII activity in control was 94.18%, whereas in non-dialysis CKD it was103.97%, and 106.18 % in haemodialysis dependent patient. haemoglobin was 13.85 gm/dl in control , but in nondialysisCKD it was 8.08 gm/dl, and in haemodialysis dependent patients 9.46 gm/dl .cardiovascular disease in nondialysisCKD 54.56% and haemodialysis dependent patients 59.4%Conclusion: Haemoglobin is low and levels of homocysteine, fibrinogen, CRP, factor-VII activity are increasedamong the patients with CKD and haemodialysis dependent patients.Key words: Non-traditional; Cardiovascular; Chronic Kidney DiseaseDOI: 10.3329/jom.v11i2.5450J MEDICINE 2010; 11 : 108-114

scholarly journals Fibrinogen: Risk Factor for Cardiovascular Disease

2012 ◽  
Vol 1 (1) ◽  
pp. 1-8
Author(s):  
Dilli Ram Kafle
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Independent Risk Factor ◽  
Diabetic Patients ◽  
Medical College ◽  
Increased Risk ◽  
Patients With Diabetes

Patients with diabetes mellitus have 2 to 4 times increased risk for cardiovascular disease than non-diabetic patients. However this excess risk is not fully explained by the traditional cardiovascular risk factors (Hypertension, Hypercholesterolaemia, Smoking and Obesity) which are also associated with diabetes. Fibrinogen has been identified as an independent risk factor for cardiovascular disease and it is associated with traditional cardiovascular risk factors. Studies done in the Caucasians have shown fibrinogen to be higher in diabetic than the non-diabetic patients. Elevated fibrinogen in diabetic patients may be responsible for the increased cardiovascular risk in those patients. Elevated fibrinogen is also associated with increased mortality in general population.DOI: http://dx.doi.org/10.3126/jonmc.v1i1.7281 Journal of Nobel Medical College Vol.1(1) 2011 1-8

scholarly journals No Increased Risk of Cataract in Immune Thrombocytopenia Adult Patients Treated with Eltrombopag. a French Nationwide Nested Case-Control Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2363-2363
Author(s):  
Margaux Lafaurie ◽  
Bérangère Baricault ◽  
Vincent Soler ◽  
Myriam Cassagne ◽  
Laurent Sailler ◽  
...  
Keyword(s):  
Risk Factors ◽  
Research Funding ◽  
Case Control Study ◽  
Case Control ◽  
Adult Patients ◽  
Cumulative Exposure ◽  
Increased Risk ◽  
Nested Case Control ◽  
Control Study

Background: In preclinical studies, eltrombopag has been associated to an increased incidence of cataract in mice and rats. No increased risk has been observed in randomized controlled trials in immune thrombocytopenia (ITP) patients. During the eltrombopag extension study EXTEND, 28/302 patients developed or worsened cataract, i.e. 9.3% of the patients over a median duration of exposure of 2.4 years. Of note, 79% of these 28 patients had at least another risk factor of cataract. Real-life studies assessing the risk of cataract in ITP adult patients exposed to eltrombopag are lacking. Aim: To assess the risk of cataract with eltrombopag in a nationwide cohort of primary ITP adults. Methods: The population was the cohort of all incident primary ITP adult patients (≥18 years) in France from June 2010 (date of eltrombopag marketing in France) to June 2017. This cohort was identified within the national health insurance database using a validated algorithm combining drug exposures and international classification of diseases, version 10 (ICD-10) diagnosis codes (FAITH cohort; NCT03429660). A nested case-control study was conducted within the cohort. Cases were patients who had a surgery for cataract after ITP onset, identified using appropriate codes. Up to five controls for each case were matched on age and sex. Index date was the date of cataract surgery for cases, and the date of cataract surgery of the corresponding case for controls. Two analyses were conducted: one considering the exposure to eltrombopag as ever vs. never exposed; another considering the cumulative exposure to eltrombopag, categorized by never exposed, a 1-365 Defined Daily Dose (DDD) exposure, and a ≥365 DDD exposure. Covariables were the presence of diabetes mellitus, cumulative exposure to corticosteroids considered in prednisone equivalence dosage (by quartiles), and the presence of ophthalmological risk factors of cataract (including previous ophthalmological surgery, glaucoma and other anterior chamber risk factors). Conditional logistic regression models were used to compute adjusted odds ratios (aOR) and their 95% confidence intervals (CI). Results: The cohort included 8,502 incident primary ITP adults. During the follow-up (31,590 patient-years in total; mean follow-up: 44.4 months), 1,097 patients were exposed to eltrombopag, including 310 with a cumulative exposure ≥365 DDDs. Overall, 573 patients had a surgery of cataract; incidence: 1.90/100 person-years (95% CI: 1.75-2.06). Fifty-seven cases occurred in patients ever exposed to eltrombopag; incidence: 1.50/100 person-years (95%CI: 1.15-1.94) in this subgroup. The nested case-control study included the 573 cases and 2699 controls. Median age was 75 years and 50% were women; the median duration of disease was 24.8 months in cases and 24.2 months in controls; 57 (9.9%) cases and 314 (11.6%) controls were exposed to eltrombopag before the index date; 14 (2.4%) and 68 (2.5%) patients had cumulative exposure to eltrombopag ≥365 DDDs, respectively. Cases were more frequently exposed to corticosteroids (83.4% vs. 75.7%), with a higher cumulative exposure to corticosteroids (median: 2800 vs. 2188 mg prednisone equivalent). Diabetes mellitus was present in 25.7% of cases vs. 25.1% of controls while ophthalmological risk factors were present in 5.4% and 2.8%, respectively. In the ever/never exposed analysis, the aOR for eltrombopag was 0.79 (95% CI: 0.58-1.07). In the cumulative exposure analysis, the aOR was 0.76 (95% CI: 0.54-1.08) in the 1-365 DDD group as compared with the never exposed group, and 0.88 (95% CI: 0.49-1.59) in the ≥365 DDD group as compared with the never exposed group. Conclusions: This nationwide pharmacoepidemiological study did not identify an increased risk of cataract in primary ITP adult patients exposed to eltrombopag. Disclosures Moulis: Novartis pharma: Research Funding, Speakers Bureau; Amgen pharma: Research Funding, Speakers Bureau; CSL Behring: Research Funding.

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