Aruna D Pradhan

Aruna D Pradhan
Partners HealthCare

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100
Publications
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Publications

Publications (100)
Article
Importance: Results of several small randomized clinical trials have suggested that supplements of marine ω-3 fatty acids may be beneficial in treating signs and symptoms of dry eye disease (DED). However, randomized clinical trial data to examine whether ω-3 fatty acid supplements can prevent DED are lacking. Objective: To evaluate whether long...
Article
Open in new tabDownload slide Graphical abstract Colchicine randomized controlled trials registered in ClinicalTrials.gov. Registered as either not yet recruiting, enrolling, or enrolling by invitation with >100 targeted enrolment. Accessed 1 March 2021. CV, cardiovascular; MI, myocardial infarction; TIA, transient ischaemic attack; CABG, coronary...
Article
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Nontraumatic lower-extremity amputation is a devastating complication of peripheral artery disease (PAD) with a high mortality and medical expenditure. There are ≈150 000 nontraumatic leg amputations every year in the United States, and most cases occur in patients with diabetes. Among patients with diabetes, after an ≈40% decline between 2000 and...
Preprint
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Background: Circulating lipid and lipoprotein levels have consistently been identified as risk factors for atherosclerotic cardiovascular disease (ASCVD), largely on the basis of studies focused on coronary artery disease (CAD). The relative contributions of specific lipoproteins to risk of peripheral artery disease (PAD) have not been well-defined...
Article
Background Triglycerides, cholesterol, and their metabolism are linked due to shared packaging and transport within circulating lipoprotein particles. While a case for a causal role of cholesterol-carrying low-density lipoproteins (LDLs) in atherosclerosis is well made, the body of scientific evidence for a causal role of triglyceride-rich lipoprot...
Article
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Importance Higher Mediterranean diet (MED) intake has been associated with reduced risk of type 2 diabetes, but underlying biological mechanisms are unclear. Objective To characterize the relative contribution of conventional and novel biomarkers in MED-associated type 2 diabetes risk reduction in a US population. Design, Setting, and Participant...
Article
Venous thromboembolism (VTE) is a major preventable disease that affects hospitalized inpatients. Risk stratification and prophylactic measures have good evidence supporting their use, but multiple reasons exist that prevent full adoption, compliance, and efficacy that may underlie the persistence of VTE over the past several decades. This policy s...
Article
Background Elevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populatio...
Article
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Background Plasma biomarkers of cardiometabolic health are invaluable tools for cardiovascular disease (CVD) and type 2 diabetes (T2D) risk stratification. Data driven patient classification may offer unbiased insights into dominant biologic risk factors that determine avenues for risk reduction. Methods We conducted an unsupervised learning (k-me...
Article
Background: Low-dose methotrexate (LD-MTX) is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis. Despite extensive clinical use for more than 30 years, few data on adverse event (AE) rates derive from randomized, placebo-controlled trials, where both causality and...
Article
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In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low le...
Article
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Background Pathologic angiogenesis is a hallmark of type 2 diabetes mellitus (T2DM) microvascular complications and may modulate adipogenesis and precede the onset of clinical diabetes mellitus; however, longitudinal data are unavailable. Placental growth factor is a potent proangiogenic factor that stimulates the formation of mature and durable ve...
Article
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Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East A...
Article
Background: Extreme sleep duration defined as either short (<6 hours) or long (>9 hours) sleep is positively associated with cardiovascular disease (CVD). Because sleep disturbance is prevalent in older women, we evaluated the relationship between extremes of sleep duration and type II diabetes (diabetes) in older women. Methods and Results: In a c...
Article
Background: Elevated triglyceride rich lipoproteins (TRLs) and small dense LDL (sdLDL) levels are hallmarks of atherogenic dyslipidemia and the cholesterol content of these particles is hypothesized to drive atherosclerotic risk. However, laboratory quantitation has thus far been impractical with limited prospective clinical data utilizing directly...
Article
Background Inflammation is causally related to atherothrombosis. Treatment with canakinumab, a monoclonal antibody that inhibits inflammation by neutralizing interleukin-1β, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial. We sought to determine whether an alternative approach to inflammation inhibition...
Article
Full-text available
Observational, genetic, and experimental data indicate that triglyceride rich lipoproteins (TRLs) likely participate causally in atherothrombosis. Yet, robust clinical trial evidence that triglyceride (TG) lowering therapy reduces cardiovascular events remains elusive. The selective peroxisome proliferator-activated receptor alpha modulator (SPPARM...
Article
Background -Despite strong and consistent prospective associations of elevated low-density lipoprotein-cholesterol (LDL-C) concentration with incident coronary and cerebrovascular disease (CCVD), data for incident peripheral artery disease (PAD) are less robust. Atherogenic dyslipidemia characterized by increased small LDL particle concentration (L...
Article
Background -The combination of statin therapy and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition markedly lowers low-density lipoprotein cholesterol (LDL-C) and reduces cardiovascular event rates. Whether residual inflammatory risk as measured by on-treatment high sensitivity C-reactive protein (hsCRP) remains an important clinica...
Article
Background: Sleep disturbances can be both a cause and consequence of circadian disruption resulting in cardiometabolic dysregulation. However, little is known about sleep debt, defined as the average sleep duration difference >=2 hours between weekend versus weekday and type II diabetes (T2D) mellitus particularly in older women. Methods and Resul...
Article
Background: Subclinical inflammation mediated in part by interleukin-1 beta (IL-1β) participates in peripheral insulin resistance and impaired pancreatic insulin secretion. Objectives: We tested the hypothesis that canakinumab, an IL-1β inhibitor, reduces incident diabetes. Methods: The Canakinumab Antiinflammatory Thrombosis Outcomes Study (C...
Article
Full-text available
Background: Subclinical myocardial injury, as measured by high-sensitivity cardiac troponin T (hsTnT), and myocardial stress, as measured by N-terminal pro-B-type natriuretic peptide (NT-proBNP), are related to glycemic control in patients with type 2 diabetes mellitus, and are strong predictors of adverse cardiovascular outcomes. We sought to det...
Article
Background: Inflammation in the tumour microenvironment mediated by interleukin 1β is hypothesised to have a major role in cancer invasiveness, progression, and metastases. We did an additional analysis in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a randomised trial of the role of interleukin-1β inhibition in atheroscle...
Article
Full-text available
Background: Type II diabetes (T2D) is preceded by prolonged insulin resistance and relative insulin deficiency incompletely captured by glucose metabolism parameters, high-density lipoprotein (HDL) cholesterol and triglycerides. Objective: Whether lipoprotein insulin resistance (LPIR) score, a metabolomic marker, is associated with incident diab...
Article
Objectives: The authors performed a meta-analysis of randomized controlled trials to compare the efficacy of initial endovascular treatment with or without supervised exercise training (SET) versus SET alone in patients with intermittent claudication. Background: Current guidelines recommend SET as the initial treatment modality for patients wit...
Article
Background: Sudden cardiac death (SCD) is often the first manifestation of cardiovascular disease (CVD) and preventive strategies within this broad population are lacking. Patients with diabetes represent a high risk subgroup, but few data exist regarding whether measures of glycemia mediate risk and/or add to SCD risk stratification. Objective:...
Article
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Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association s...
Article
Full-text available
Funding for this study was provided by the Academy of Finland (41071, 117787, 118065, 121584, 124282, 126925, 129494, 129322, 129378, 130326, 134309, 134791, 136895, 139635, 250207, 263836, 286284 and 263924); Ahokas Foundation; ALF/LUA research grant in Gothenburg; Amgen; Augustinus Foundation; Becket Foundation; Bristol-Myers Squibb; British Hear...
Article
Introduction: Current guidelines recommend supervised exercise training (SET) as the initial treatment modality for patients with intermittent claudication (IC), in addition to optimal medical therapy. The role of endovascular revascularization (ER) as a primary treatment option has been controversial. We performed a meta-analysis to compare the ef...
Article
Alcohol use, physical activity, diet, and cigarette smoking are modifiable cardiovascular risk factors that have a substantial impact on the risk of myocardial infarction, stroke, and cardiovascular death. We hypothesized that these behaviors may alter concentrations of cardiac troponin, a marker of myocyte injury, and B-type natriuretic peptide, a...
Conference Paper
Introduction: Diabetes mellitus (DM) is a strong risk factor for cardiovascular disease (CVD), a known risk factor for sudden cardiac death (SCD). Diabetes status and elevated fasting plasma glucose levels are associated with SCD; however, the association between long term hyperglycemia as measured by hemoglobin A1c (HbA1c) and risk of SCD, indepen...
Article
Natriuretic peptides are positively associated with incident cardiovascular disease (CVD), but data in women, particularly with regard to improvements in risk prediction, are sparse. We measured the N-terminal prohormone form of B-type natriuretic peptide (NT-proBNP) in 480 cases of incident CVD (myocardial infarction, stroke, and cardiovascular de...
Article
Enzymatically glycosylated proteins partake in multiple biological processes, including glucose transport and inflammation. We hypothesized that a novel biomarker (GlycA) of N-acetyl methyl groups originating mainly from N-acetylglucosamine moieties of acute-phase glycoproteins is related to incident type 2 diabetes mellitus and compared it with hi...
Article
Despite continued appreciation of the potential role of vitamin D and omega-3 fatty acids in the prevention of cancer and cardiovascular disease (CVD), there remain no completed large-scale, randomized trials of these agents for the primary prevention of cancer or CVD in a population that has not been selected on the basis of elevated risk. The vit...
Article
Full-text available
Once atrial fibrillation (AF) progresses to sustained forms, adverse outcomes increase and treatment success rates decrease. Therefore, identification of risk factors predisposing to persistence of AF may have a significant impact on AF morbidity. We prospectively examined the differential associations between traditional, lifestyle, and biomarker...
Article
Background: The metabolic syndrome is a clinical condition characterized by the presence of multiple interrelated risk factors for type 2 diabetes and cardiovascular disease. Component features include dysglycemia, increased blood pressure, increased triglycerides, decreased HDL cholesterol concentrations, and obesity (in particular, abdominal obe...
Article
Full-text available
Inflammation plays a fundamental role in atherothrombosis. Yet, whether direct inhibition of inflammation will reduce the occurrence of adverse cardiovascular outcomes is not known. The Cardiovascular Inflammation Reduction Trial (CIRT) (ClinicalTrials.govNCT01594333) will randomly allocate 7,000 patients with prior myocardial infarction (MI) and e...
Article
Background: Animal data suggest that natriuretic peptides play an important role in energy metabolism, but prospective studies evaluating a relationship between these peptides and type 2 diabetes mellitus (T2DM) in humans are few and results are conflicting. Methods: We used a prospective case-cohort approach (n = 491 T2DM cases, n = 561 referen...
Article
Background: In view of evidence that statin therapy increases risk of diabetes, the balance of benefit and risk of these drugs in primary prevention has become controversial. We undertook an analysis of participants from the JUPITER trial to address the balance of vascular benefits and diabetes hazard of statin use. Methods: In the randomised, d...
Article
The purpose of this study was to assess whether changes of major atrial fibrillation (AF) risk factors and/or intercurrent cardiovascular events could explain the relationship between type 2 diabetes mellitus (T2D) and incident AF. Previous studies found an increased risk of incident AF among individuals with T2D, but few, if any, of these studies...
Article
In view of evidence that statin therapy increases risk of diabetes, the balance of benefit and risk of these drugs in primary prevention has become controversial. We undertook an analysis of participants from the JUPITER trial to address the balance of vascular benefits and diabetes hazard of statin use. In the randomised, double-blind JUPITER tria...
Article
Background: Previous cross-sectional studies evaluating the relationship between diabetes prevalence and migraine status have found conflicting results. We examined the relationship between migraine and incident type 2 diabetes (T2D) in a cohort of adult women. Methods: Prospective cohort study conducted among participants in the Women's Health...
Article
Multiplex immunoassays are increasingly used in epidemiologic studies to measure inflammatory factors, however there are few published evaluations of this technology. Our objective was to compare a common multiplex immunoassay to singleplex immunoassays for measuring inflammatory factors, and to examine how combining data from each affects an epide...
Data
A/B: Mediation Analysis of individual and composite risk factors and their association with the SES-Incident Diabetes Relationship. (DOC)
Article
Full-text available
We prospectively examined whether socioeconomic status (SES) predicts incident type II diabetes (diabetes), a cardiovascular risk equivalent and burgeoning public health epidemic among women. Participants include 23,992 women with Hb(A1c) levels <6% and no CVD or diabetes at baseline followed from February 1993 to March 2007. SES was measured by ed...
Article
Adiponectin is linked to reduced diabetes risk and may be antiatherogenic, yet clinical data show no consistent relationship with incident cardiovascular events, especially among women. To our knowledge, no prior prospective studies have evaluated adiponectin, including high-molecular-weight (HMW) adiponectin, and incident peripheral artery disease...
Article
Full-text available
Prospective data regarding risk factors for peripheral artery disease (PAD) are sparse, especially among women; the relative contribution of systolic versus diastolic blood pressure control for incident PAD has not been well studied. We evaluated the association of self-reported blood pressure control with incident symptomatic PAD in middle-aged an...
Article
Full-text available
It is unclear whether models that include hemoglobin A(1c) (HbA(1c)) levels only for diabetic patients improve the ability to predict cardiovascular disease (CVD) risk compared with the currently recommended classification of diabetes as a cardiovascular risk equivalent. A total of 24 674 women (including 685 diabetic participants at baseline) and...
Article
Very low levels of cardiac troponin T are associated with an increased risk of cardiovascular death in patients with stable chronic coronary disease. Whether high-sensitivity cardiac troponin T levels are associated with adverse cardiovascular outcomes in individuals without cardiovascular disease (CVD) has not been well studied. Using 2 complement...
Article
Background: Smoking has a well-documented detrimental effect on risk for myocardial infarction and stroke, but less information is available regarding peripheral artery disease (PAD), particularly among women. Objective: To prospectively assess the association of current smoking status, cumulative smoking exposure, and smoking cessation with inc...
Article
Smoking has a well-documented detrimental effect on risk for myocardial infarction and stroke, but less information is available regarding peripheral artery disease (PAD), particularly among women. To prospectively assess the association of current smoking status, cumulative smoking exposure, and smoking cessation with incident symptomatic PAD in w...
Article
Although basic research has implicated abnormal glucose metabolism in the pathogenesis of hypertension (HTN), epidemiologic studies are limited. We assessed whether baseline hemoglobin A(1c) (HbA(1c)) was prospectively associated with HTN in the Women's Health Study (WHS). We analyzed 19,858 women initially free of HTN, diabetes, and cardiovascular...
Article
Full-text available
Diabetic dyslipoproteinemia is characterized by low HDL cholesterol and high triglycerides. We examined the association of lipoprotein particle size and concentration measured by nuclear magnetic resonance (NMR) spectroscopy with clinical type 2 diabetes. This was a prospective study of 26,836 initially healthy women followed for 13 years for incid...
Article
The metabolic syndrome (MetS) is associated with incident myocardial infarction and stroke and is linked with subclinical inflammation; however, prospective data pertaining to MetS and future peripheral artery disease (PAD) are sparse, with few studies examining the role of inflammation. We therefore evaluated the relationship between MetS, inflamm...
Article
As diabetes is in part an inflammatory condition, the initiation of insulin and/or metformin may beneficially reduce levels of inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP). To determine whether insulin alone or combined with metformin lowers levels of hsCRP, IL-6, and soluble tumor necrosis factor receptor 2 (sTNFr2)...
Article
Full-text available
Genetic variation of the estrogen receptor alpha (ESR1) and beta (ESR2) has been associated with components of the metabolic syndrome. The relationships of two ESR1 (rs2234693 and rs9340799) and three ESR2 (rs1271572, rs1256049, and rs4986938) polymorphisms with the metabolic syndrome were examined in 532 Caucasian female participants (median age 6...
Article
The latter half of the 20th century has witnessed rapid advances in medicine. Concurrently, secular trends in lifestyle practices in our increasingly sedentary society have led to burgeoning rates of obesity, metabolic syndrome, and type 2 diabetes. The number of Americans with type 2 diabetes more than doubled between 1980 and 2004 and the prevale...
Article
Subclinical inflammation is linked with the development of type 2 diabetes, and epidemiologic data suggest that this association may be stronger in women. Although small clinical studies have shown a prominent hypoglycemic effect of short-term high-dose aspirin, no randomized trials have directly evaluated the efficacy of aspirin in diabetes preven...
Article
Most current methods for normalizing cardiac dimensions for differences in body size assume a linear isometric relationship between variables. This approach may be flawed. We therefore compared the isometric and allometric modeling approach to assess the optimal scaling method (using the left atrial dimension [LAD] as an example) in a large group o...
Article
It is general practice to correct cardiac chamber size for body size by the process of scaling or normalization. Normalization is most commonly performed using simple linear or isometric correction; however, there is increasing evidence that this approach may be flawed. Likewise, there is little agreement concerning the appropriate scaling variable...
Article
Most investigations of novel biomarkers for prediction of cardiovascular disease pertain to coronary artery disease. Few large-scale prospective studies have critically assessed plasma-based factors as predictors of peripheral arterial disease (PAD), and comparative data between individual biomarkers and lipid levels are sparse, especially among wo...
Article
Using a transcriptional profiling approach, we recently identified myeloid-related protein 8/14 (MRP-8/14) to be expressed by platelets during acute myocardial infarction (MI). Elevated concentrations of MRP-8/14 are associated with a higher risk for future cardiovascular events in apparently healthy individuals but have not been assessed with resp...
Article
In a recent study, Rhodes et al. (1) questioned the accuracy of administrative coding for type 2 diabetes in children and young adults, noting a very low positive predictive value (PPV) of 16.6%. The article also highlighted the importance of adopting standardized and validated diagnostic protocols in epidemiologic studies. Using diagnostic criter...