Berberine: A Multi-Target Natural PCSK9 Inhibitor with the Potential to Treat Diabetes, Alzheimer's, Cancer and Cardiovascular Disease.

Berberine is a natural product with a wide range of pharmacological effects. It has antimicrobial, anti-cancer, anti-inflammatory, anti-hyperlipidemic, neuroprotective, and cholesterollowering properties, among others. It has been used in traditional Chinese and Ayurvedic medicine for 3000 years and is generally well-tolerated with few side effects. Its main drawback is low oral bioavailability, which has hindered widespread clinical use. However, recent interest has surged with the emergence of evidence that berberine is effective in treating cancer, diabetes, Alzheimer's disease, and cardiovascular disease via multiple mechanisms. It enhances insulin sensitivity and secretion by pancreatic ß-cells in Type 2 Diabetes Mellitus in addition to reducing pro-inflammatory cytokines such as IL-6, IL-1ß, TLR4 and TNF-α. These cytokines are elevated in Alzheimer's disease, cardiovascular disease, and diabetes. Reductions in pro-inflammatory cytokine levels are associated with positive outcomes such as improved cognition, reduced cardiovascular events, and improved glucose metabolism and insulin sensitivity. Berberine is a natural PCSK9 inhibitor, which contributes to its hypolipidemic effects. It also increases low-density lipoprotein receptor expression, reduces intestinal cholesterol absorption, and promotes cholesterol excretion from the liver to the bile. This translates into a notable decrease in LDL cholesterol levels. High LDL cholesterol levels are associated with increased cardiovascular disease risk. Novel synthetic berberine derivatives are currently being developed that optimize LDL reduction, bioavailability, and other pharmacokinetic properties.

Association Between Idiopathic Thrombocytopenic Purpura and Hemorrhagic and Nonhemorrhagic Stroke.

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is characterized by a low platelet count. This may lead to an increased risk of hemorrhagic stroke but a lower rate of nonhemorrhagic stroke. The goal of this study was to evaluate the association between ITP and both hemorrhagic and nonhemorrhagic strokes using a large database. METHODS: We used the Nationwide Inpatient Sample (NIS) database to analyze the occurrence of hemorrhagic and nonhemorrhagic stroke in patients with and without a diagnosis of ITP from 2005 to 2014. RESULTS: Univariate analysis revealed a higher incidence of hemorrhagic stroke in patients with ITP in the year studied. (for example, in 2005: OR, 1.75; 95% CI, 1.57-1.94; P < 0.001; 2014: OR, 2.19; 95% CI, 2.03-2.36; P < 0.001). After adjusting for age, gender, race, and hypertension, hemorrhagic stroke remained significantly associated with ITP (in 2005: OR, 1.85; 95% CI, 1.49-1.89; P < 0.001; 2014: OR, 2.01; 95% CI, 1.86-2.18; P < 0.001) for all the years studied. Nonhemorrhagic stroke occurred at a lower rate in patients with ITP in most years (2006: OR, 0.91; 95% CI, 0.85-0.97; P = 0.004; 2014: OR, 0.88; 95% CI, 0.83-0.93; P < 0.001). Multivariate analysis confirmed a higher rate of nonhemorrhagic stroke in ITP patients. CONCLUSION: Our analysis showed that there was a higher rate of hemorrhagic stroke but a lower rate of ischemic stroke in ITP patients, suggesting an important role of platelets in the occurrence of stroke.

Gender based disparity in performing aortic valve surgery in the united state before availability of percutaneous valve implantation.

BACKGROUND: Aortic valve surgery has been performed increasingly in high-risk patients. The goal of this study was to evaluate this trend based on gender in the United States before the availability of percutaneous aortic valve replacement. METHOD: The Nationwide Inpatient Sample (NIS) database was utilized to calculate the age-adjusted utilization rate for aortic valve surgery from 1988 to 2011 in the United States using ICD-9 coding for aortic valve surgery. RESULTS: A total population of 258, 506 patients underwent aortic valve between 1988-2011 were available for our study over the age of 20. We found that the age-adjusted rate of aortic valve surgery gradually increased from 1988 until 2009 and stabilized thereafter with a persistently higher rate for men. For men age-adjusted rate in 1988 was 13.3 per 100,000 vs. 27.0 in year in the year 2011 per 100,000. For women, the age-adjusted rate in 1988 was 6.07 per 100,000 vs. 11.4 in year 2011 per 100.000). CONCLUSION: Aortic valve surgery utilization has stabilized in recent years in both genders in the United States. However, this rate has been persistently more than double in men. The cause of this higher utilization in males needs further investigation.

Higher Heart Rate Is Independently Associated With Abnormal Body Mass Index in a J Shape Pattern.

BACKGROUND: High heart rate (HR) is independently associated with higher cardiovascular mortality and usually occurs in sedentary persons. Inactivity can also lead to obesity. The purpose of this study was to evaluate the associations between body mass index as an independent marker of high HR. METHOD: Data generated from screening echocardiography, for the prevention of sudden death at the Anthony Bates Foundation, was used. Data from 1340 subjects, with documented HR and body mass index, between the ages 19-79 years with a mean age of 32 years, were studied. We correlated the presence of a high HR >90 beats per minute (bpm) with different body mass index (BMI) categories. RESULTS: High HR was significantly associated with higher BMI categories and underweight subjects in adults suggesting a J shape association. A total of 22.7% of participants with an HR of more than 90 bpm had BMI >40 kg/m 2 , versus 19.0% of patients with BMI of 35-40 kg/m 2 versus 13.5% of subjects with BMI of 30-35 kg/m 2 versus 12.2% of subjects with BMI of 25-30 kg/m 2 -29.9 kg/m 2 , versus in 10.3% of subjects with BMI between 18.5 and 25 kg/m 2 , P < 0.01) Furthermore, increased HR was also more prevalent in underweight patient (17.4% in subjects with BMI < 18.5 kg/m 2 ). CONCLUSION: High HR is strongly associated with obesity and underweight suggesting that maintaining a normal weight is associated with most positive effect on the cardiovascular system.

The Presence of Pneumonia Is Strongly Associated With Higher Prevalence of Non-ST-Elevation Myocardial Infarction Using a Large NIS Database.

OBJECTIVE: Inflammation is a risk factor for myocardial infarction. Pneumonia leads to severe inflammatory response. Some studies suggest higher risk of myocardial infarction in patients with pneumonia. We used a large inpatient database (National Inpatient Sample) to evaluate this association. METHODS: This study includes patients from a Nationwide Inpatient Sample hospital in 2005 to 2014 with International Classification of Diseases, Ninth Revision, and Clinical Modification codes consistent with pneumonia and non-ST elevation myocardial infarction (NSTEMI). Subjects were stratified into all hospitalized patients aged 30 and above. Univariate and multivariate analysis was performed adjusting for age, race, gender, tobacco use, diabetes mellitus, hypertension, and hyperlipidemia. RESULTS: NSTEMI was present in 3.2% of pneumonia patients versus 1.8% in the non-pneumonia population over 10-year period. For example, the 2005 database: [odds ratio (OR), 1.77; 95% confidence interval (CI), 1.73-1.80; P < 0.001]. For 2014, NSTEMI was present in 4.1% of pneumonia patients (PNA) versus 2.4% in the non-pneumonia population (OR, 1.72; 95% CI, 1.70-1.75; P < 0.001). NSTEMI remained independently associated with pneumonia following a multivariate analysis in 2005 (OR, 1.477; 95% CI, 1.447-1.508; P < 0.001) with a similar value in 2014 (OR, 1.445; 95% CI, 1.421-1.469; P < 0.001). CONCLUSIONS: Using a large inpatient database, we found that NSTEMI was strongly associated with PNA versus non-pneumonia population over a 10-year period. Suggesting acute inflammatory cytokines or hypoxia which occurs during lung infection may play a role in NSTEMI development, reinforcing the importance of acute cardiac monitoring in patients with PNA.

A comprehensive review of the ten main platelet receptors involved in platelet activity and cardiovascular disease.

Cardiovascular disease (CVD) is a major cause of death worldwide. Although there are many variables that contribute to the development of this disease, it is predominantly the activity of platelets that provides the mechanisms by which this disease prevails. While there are numerous platelet receptors expressed on the surface of platelets, it is largely the consensus that there are 10 main platelet receptors that contribute to a majority of platelet function. Understanding these key platelet receptors is vitally important for patients suffering from myocardial infarction, CVD, and many other diseases that arise due to overactivation or mutations of these receptors. The goal of this manuscript is to review the main platelet receptors that contribute most to platelet activity.

Association between Factor-V Leiden and occurrence of acute myocardial infarction using a large NIS database.

Factor V Leiden is an inheritable pro-thrombotic genetic condition caused by a point mutation at the 506th codon, resulting in activated protein C resistance. APC resistance has been shown to contribute to the development of venous thrombosis. However, the role of FVL in AMI has yet to be well defined in the current literature. To assess whether a mutation carrier is more apt to develop an AMI, we conducted a retrospective observational analysis of two populations aged 18-40 and 18 through end of life. We used ICD-10 codes to search the NIS, an electronic nationwide patient database, to establish our populations and obtain our data. The ICD-10 codes were specific for activated protein C resistance and acute myocardial infarction. Preliminary data indicated that FVL was related to AMI; however, this finding became insignificant in both populations when stratified for age. We concluded there was no association between Factor V Leiden and acute myocardial infarction across both examined populations. Future investigations into this field of research are warranted as there remains a need for more consensus among the scientific community. BACKGROUND: Medical literature regarding the correlation between Factor V Leiden (FVL) and acute myocardial infarctions (AMI) is controversial. We aim to investigate the association between FVL and AMI. MATERIALS AND METHODS: Using the Nationwide Inpatient Sample database, we evaluated any association between Factor V Leiden and acute myocardial infarction in 2016 using ICD-10 codes. RESULTS: Univariate analysis (18-40) showed an increase of AMI in patients with FVL 0.6% vs. 0.4%. However, after adjustment for age and comorbid conditions in multivariate analysis, FVL was not significantly associated with acute myocardial infarction (OR 1.44 (95% CI 0.913-2.273, p-value 0.117)). Univariate analysis (all patients over 18 years old) found that 2.9% of patients with FVL experienced AMI vs. 4.4% without the mutation. Multivariate analysis of the entire population ultimately showed no correlation between FVL and AMI. CONCLUSION: In a population over 18, Factor V Leiden did not correlate with an increased risk of acute myocardial infarction in our studied population.

All Aortic Valve Diseases Taken Together Are Not Associated With Obesity.

BACKGROUND: Obesity is a risk factor for cardiovascular disease. The goal of this study was to evaluate any association between aortic valve disease and obesity using a very large database. METHODS: The Nationwide Inpatient Sample database was utilized for statistical analysis using ICD-9 codes for aortic valve disease and obesity in the United States from 2003 to 2007. A 25% random sample of nonobese patients was used for comparison of aortic valve disease prevalence during the same 5-year period. RESULTS: A total of 1,971,812 patients with obesity were identified from 2003 to 2007. Comparing this population with a random sample of nonobese patients during the same years, there was no significant difference between obese and nonobese patients in regards to the prevalence of aortic valve disease (1.1-1.2% in 2003 and 2004, 1.2% in 2005-2007, P = NS). After adjusting for age, gender, and race, obesity was associated with lower prevalence of aortic valve disease in 2003-2007 (odds ratio 0.81-0.86, P < 0.01). CONCLUSIONS: Using a very large database, we found a decrease in the prevalence of aortic valve disease in the obese population. This suggests that obesity alone does not pathologically affect the aortic valve.

Splenectomy in patients with immune (idiopathic) thrombocytopenic purpura (ITP) appears to be protective against developing aortic valve disease.

BACKGROUND: Immune thrombocytopenia (ITP) has been shown to be independently associated with aortic valve disease (AVD). However, whether ITP patients who have undergone splenectomy are also at increased risk for AVD has not been researched. The goal of this study was to evaluate any association between AVD and splenectomy in patients with ITP. METHOD: We used the Nationwide Inpatient Sample from 2005 to 2014 as 10 consecutive years randomly selected. Using ICD-9 codes for AVD, ITP, and splenectomy, a total of 108,434 patients were identified with ITP, 4,282 of which had undergone splenectomy. We performed uni- and multivariate analysis adjusting for baseline characteristics. RESULTS: Univariate analysis revealed a significantly lower rate of AVD in ITP patients with splenectomy compared to no splenectomy in 2007, 2009, and 2010 with a trend of this association during the other years. For example, in 2007, 0.6% of ITP patients with history of splenectomy had AVD versus 2.0% of ITP patients without splenectomy (OR, 0.29; 95% CI, 0.09-0.91; P = 0.02). Similarly, in 2010, 0.2% of ITP patients with history of splenectomy had AVD versus 1.9% of ITP patients without splenectomy (OR, 0.13; 95% CI, 0.02-0.92; P = 0.02). After adjusting for age, gender, race, diabetes, hypertension, hyperlipidemia, and tobacco use, we confirmed that ITP patients with splenectomy have no association with prevalence of aortic valve disease (2005: OR, 0.48; 95% CI, 0.18-1.30; P = 0.15; 2014: OR, 0.88; 95% CI, 0.36-2.16; P = 0.77). CONCLUSION: Based on a large inpatient database, our previous finding of ITP patients' association with AVD is only present in patients without splenectomy, and splenectomy appears to exert a protective effect on developing aortic valve disease in ITP patients, warranting further investigation.

A Comprehensive Review of PCSK9 Inhibitors.

Cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. A major risk factor for this condition is increased serum low-density lipoprotein cholesterol (LDL-C) levels for which statins have been successful in reducing serum LDL-C to healthy concentrations. However, patients who are statin intolerant or those who do not achieve their treatment goals while on high-intensity statin therapy, such as those with familial hypercholesterolemia, remain at risk. With the discovery of PCSK9 inhibitors, the ability to provide more aggressive treatment for patients with homozygous and heterozygous familial hypercholesterolemia has increased. Ezetimibe reduces LDL-C by 15%-20% when combined with statin.2,3 Protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been found to achieve profound reductions in LDL-C (54%-74%) when added to statins. They have shown dramatic effects at lowering major adverse cardiovascular events (MACE) in high-risk patients4 with LDL-C levels ≥70 mg/dL and can be used in populations that are statin intolerant or not at goal levels with maximally tolerated statin therapy. PCSK9 inhibitors also produce minimal side effects. Myopathy, a common side effect for patients on statins, has been rare in patients on PCSK9 inhibitors. Randomized trials have shown that reduction in LDL-C has translated to clinical benefits even in patients who have not achieved their LDL-C target.

The effects of estrogen and hormone replacement therapy on platelet activity: a review.

Many studies have shown that an increase in cardiovascular disease in women is related to hormonal changes occurring particularly after menopause with increasing age. While the results of large clinical trials reporting no benefit of hormone replacement therapy (HRT) in cardiovascular disease have been known for some time, there is an increasing body of knowledge regarding the various mechanisms by which estrogen modulates platelet function that could in part explain the higher cardiovascular risk occurring in postmenopausal women and potential benefits of HRT on cardiovascular health. Our review summarizes our current knowledge regarding the effect of endogenous and exogenous estrogen on platelet activity, which can help researchers design future studies. We collected information from 21 peer-reviewed articles published from 1993 to 2021. Studies have indicated that postmenopausal women have higher platelet activity than premenopausal women, which can increase the risk of thrombo-embolic events and cardiovascular disease. Although some studies have reported pro-thrombotic effects of estrogen replacement therapy such as increased platelet activation and adhesion, other studies demonstrated decreased platelet aggregation by inhibiting GP IIb/IIIa receptor expression. This is mediated by estrogen receptors on the platelet membrane in a non-genomic manner and suggests an opportunity for the usage of estrogen replacement therapy with subtle changes in the formulation and route, particularly if started early after menopause. The effect of estrogen on platelet activity is promising as an important factor in reducing the risk of cardiovascular events, warranting further investigation.

Left ventricular hypertrophy is independently associated with all-cause mortality.

BACKGROUND: Left Ventricular Hypertrophy (LVH) is associated with adverse outcomes. The goal of this study was to evaluate any association between LVH and all-cause mortality using a large echocardiographic database. METHODS: We retrospectively evaluated 2,352 echocardiograms between the ages 16-99 years that were performed from 1983 to 1998 for clinical reasons in Southern California. Mortality data were extracted from the national mortality database at the end of the year 2007. Using uni- and multi-variant analysis, we evaluated any association between total mortality and echocardiographic presence of LVH defined as any wall thickness >11 mm. RESULTS: LVH was significantly associated with all-cause mortality [207/583 (35.5%) of patients died with LVH vs. 416/1769 (23.5%) of patients with normal wall thickness, P<0.001, HR 1.79, CI: 1.46-2.19]. Using multivariate analysis adjusting for age, gender, abnormal left ventricular systolic function, and significant valvular abnormalities, LVH remained independently associated with all-cause mortality (OR 1.39, CI 1.10-1.74, P=0.005). CONCLUSION: Using a large echocardiographic database, we found that LVH is independently associated with all-cause mortality. Our finding confirms the negative effect of LVH on the long-term outcome.

The presence of idiopathic thrombocytopenic purpura and incidence of acute non-ST elevation myocardial infarction.

Platelets play an integral role in the pathogenesis of acute coronary syndrome (ACS). The purpose of this study was to investigate any correlation between immune thrombocytopenia (ITP) and non-ST segment elevation myocardial infarction (NTSEMI), a common presentation of ACS. Using the large Nationwide Inpatient Sample (NIS) database, we studied any correlation between NSTEMI and ITP utilizing ICD-9 codes. We performed uni- and multivariate analysis adjusting for risk factors from the years 2002-2011. Data was extracted from 106,653 ITP patients and 79,636,090 controls. In multiple years of the study period (2002-2011), NSTEMI incidence was significantly higher in ITP patients when compared with non-ITP patients in the univariate analysis (odds ratio average 1.226). However, no significant association was found after adjusting for additional risk factors in multivariate analysis. Based on our large database study, ITP is not independently associated with NSTEMI incidence after adjusting for comorbidity.

Design, Synthesis, and In Vitro and In Vivo Evaluation of Novel Fluconazole-Based Compounds with Promising Antifungal Activities.

Demand has arisen for developing new azole antifungal agents with the growth of the resistant rate of infective fungal species to current azole antifungals in recent years. Accordingly, the present study reports the synthesis of novel fluconazole (FLC) analogues bearing urea functionality that led to discovering new azole agents with promising antifungal activities. In particular, compounds 8b and 8c displayed broad-spectrum activity and superior in vitro antifungal capabilities compared to the standard drug FLC against sensitive and resistant Candida albicans (C. albicans). The highly active compounds 8b and 8c had potent antibiofilm properties against FLC-resistant C. albicans species. Additionally, these compounds exhibited very low toxicity for three mammalian cell lines and human red blood cells. Time-kill studies revealed that our synthesized compounds displayed a fungicidal mechanism toward fungal growth. Furthermore, a density functional theory (DFT) calculation, additional docking, and independent gradient model (IGM) studies were performed to analyze their structure-activity relationship (SAR) and to assess the molecular interactions in the related target protein. Finally, in vivo results represented a significant reduction in the tissue fungal burden and improvements in the survival rate in a mice model of systemic candidiasis along with in vitro and in silico studies, demonstrating the therapeutic efficiency of compounds 8b and 8c as novel leads for candidiasis drug discovery.

Evaluating association between idiopathic thrombocytopenic purpura and hypertension.

PURPOSE: The role of platelets in the pathogenesis of hypertension is not well known. The aim of this study was to ascertain if patients with immune thrombocytopenia (ITP) had different rates of hypertension. MATERIALS AND METHODS: Using the Nationwide Inpatient Sample (NIS) database, we analyzed the correlation between hypertension and ITP from the years 2002-2011. RESULTS: We found no significant differences in the rate of hypertension between ITP and Non-ITP patients. For instance, in 2002, 25.90% of patients with ITP had a concurrent diagnosis of hypertension, compared with 26.53% of Non-ITP patients. Then in 2011, 31.95% of patients with ITP had a concurrent diagnosis of hypertension, compared with 32.31% of Non-ITP patients. CONCLUSION: Based on our large database, the presence of ITP does not appear to be associated with an increased or decreased risk of hypertension.

The presence of idiopathic thrombocytopenic purpura correlates with lower rate of acute ST-elevation myocardial infarction.

Background: Platelets are important in the pathogenesis of myocardial infarction (MI). We hypothesize that patients with acquired thrombocytopenia such as idiopathic thrombocytopenic purpura (ITP) may have lower MI rate. Materials & method: The Nationwide Inpatient Sample was used for this study. We analyzed the correlation between ST-elevation MI (STEMI) and ITP utilizing ICD-9 codes. Results: STEMI rate was lower in patients with ITP. We found that, in 2002, STEMI occurred in 0.64% of patients with ITP versus 0.89 (p < 0.007) and for 2011 0.30 versus 0.48 (p < 0.005). After adjusting for tobacco use, diabetes, hypertension, hyperlipidemia, gender and age, STEMI rate remained lower in ITP patients. Conclusion: ITP appears to be associated with lower STEMI rate suggesting low platelet count may exert protective effect from STEMI.

The effects of estrogen and hormone replacement therapy on cardiovascular systems.

Postmenopausal women have an increased risk of cardiovascular disease, which is believed to correlate with lower estrogen level. There are conflicting data regarding hormone replacement therapy (HRT) based on the timing of this therapy. After large randomized trials showed no cardiovascular benefit of hormone replacement, estrogen replacement therapy was dramatically reduced even though starting hormone replacement in early postmenopausal period had shown significant benefit. There are hardly any reviews discussing in detail the effect of HRT on cardiovascular system while briefly discussing other effects of this therapy in postmenopausal women. The novelty of this review is the comprehensive discussion of this effect that can help researchers and clinicians to design future research or trials. In this manuscript, the effect of HRT on cardiovascular system in clinical trials and basic science will be reported and potentially erroneous conclusions drawn by various studies will be discussed. Furthermore, various noncardiovascular effect of HRT will be analyzed.

Persistent reduction in the age adjusted mortality rate from aortic valve surgery in the United State with elimination of gender gap in recent years.

BACKGROUND: Advancement in the surgical techniques should translate into better outcome. The goal of this study was to evaluate mortality trends from aortic valve surgery in the United State using large inpatient database. METHOD: The Nationwide Inpatient Sample (NIS) database was used to calculate the age-adjusted mortality rate from aortic valve surgery from 1988 to 2011 in the United State using ICD-9 coding for aortic valve surgery. RESULTS: We found that age adjusted mortality rate from aortic valve surgery gradually decreased from 1988 until end of study in 2011 to the lowest level with elimination of gender gap that was seen in the early years. For men, age adjusted mortality rate from aortic valve surgery in 1988 was 438 per 100,000 with steady reduction to the lowest level of 214 per 100,000 in 2011 which remained unchanged from 2007. For women, age adjusted mortality from aortic valve surgery was 620 per 100,000 in 1988 with steady reduction to the lowest level of 235 per 100,000 in 2011 which also remained unchanged since 2007. CONCLUSION: Age adjusted mortality from aortic valve surgery has been gradually decreasing in the last decade and remained stable at the lowest rates in recent years suggesting improvement in surgical technics and post-surgical care.

History of the development of antifungal azoles: A review on structures, SAR, and mechanism of action.

With the increasing risk of invasive and life threating fungal infections, there is now a great concern regarding the lower discovery rate of antifungal drugs in comparison to antimicrobial agents. Drugs conventionally used in clinics are not adequate enough to combat the increasing fungal infections, especially fungal forms resistant to fluconazole. Among the limited antifungal agents in clinics, azoles have the largest number of drug candidates in clinical trials and are partly marketed due to the particular focus of pharmaceutical companies and medicinal scientific centers. With the rise in the number of papers on azole antifungal design and discovery, a more in-depth understanding the most recent and authentic information about this class of drugs might be beneficial. To this end, we for the first time summarized the state-of-the-art information about azole drugs, with a specific focus on those in the pipelines of pharmaceutical companies, into four generations with regard to their structural similarity. More importantly, this review highlights information on the structure activity relationship (SAR), target description, hybrid antifungal agents as possible future generation, and other useful issues to streamline research towards designing new efficient azole antifungal structures in future.

Idiopathic thrombocytopenic purpura is strongly associated with higher prevalence of aortic valve disease.

Aortic valve disease (AVD) has similarities to atherosclerosis in the case of aortic stenosis. The important role of platelet in the pathogenesis of atherosclerosis is known. The goal of this study is to evaluate whether platelet disorders play any role in aortic valve disease. We used patients with idiopathic thrombocytopenic purpura (ITP) for this study. We evaluated any association between ITP and AVD using a large inpatient database. The International Classification of Diseases, Ninth Revision, and Clinical Modification (ICD-9-CM) codes for ITP and AVD from the Nationwide Inpatient Sample (NIS) database were used for this study. Uni- and multivariate analyses were performed on data from 2002 to 2011 to evaluate any association between ITP and AVD. In the 2002 database, AVD was present in 1.73% of ITP patients versus 1.12% in the control population (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.34-1.81; p < 0.001). In the 2011 database, AVD was present in 1.96% of ITP patients versus 1.33% in the control population (OR, 1.48; 95% CI, 1.30-1.68; p < 0.001). ITP remained independently associated with AVD following a multivariate logistic regression analysis adjusting for age, gender, diabetes mellitus, hypertension, and hyperlipidemia in 2002 (OR, 1.35; 95% CI, 1.16-1.57; p < 0.001) with a trend of this association in 2011 (OR, 1.12; 95% CI, 0.98-1.27; p = 0.096). ITP was strongly associated with AVD over the 10-year period analyzed in a large inpatient database. The reason for this association is not known warranting further investigations.