Sunita Dodani

Can dysfunctional HDL explain high coronary artery disease risk in South Asians

BACKGROUND Coronary artery disease (CAD) is the leading cause of mortality and morbidity in United States, and South Asian immigrants (SAIs) have a higher risk for CAD compare to Caucasians. Traditional risk factors do not completely explain high risk, and some of the unknown risk factors need to be explored. We assessed dysfunctional pro-inflammatory high density lipoprotein (HDL) in SAIs and assessed its association with sub-clinical CAD using carotid intima-media thickness (IMT) as a surrogate marker for atherosclerosis. METHODS Cross-sectional study on SAIs aged 40-65 years. Sub-clinical CAD was measured using carotid intima media thickness (IMT) as a surrogate marker of atherosclerosis. Dysfunctional or pro-inflammatory HDL was determined by novel cell free assay and HDL inflammatory Index. RESULTS Dysfunctional HDL was found in the 50% participants, with HDL-inflammatory index of >or=1.00, suggesting pro-inflammatory HDL (95% CI, 0.8772-1.4333). The prevalence of sub-clinical CAD using carotid IMT (>or=0.80 mm) was seen in 41.4% (95% CI, 0.2347-0.5933). On logistic regression analysis, positive carotid IMT was found to be associated with dysfunctional HDL after adjusting for age, family history of cardiovascular disease, and hypertension (p=0.030). CONCLUSIONS The measurement of HDL level as well as functionality plays an important role in CAD risk assessment. Those SAIs with dysfunctional HDL and without known CAD can be a high risk group requiring treatment with lipid lowering drugs to reduce future risk of CAD. Further large studies are required to explore association of dysfunctional HDL with CAD and identify additional CAD risk caused by dysfunctional HDL.

Carotid intima media thickness and low high-density lipoprotein (HDL) in South Asian immigrants: could dysfunctional HDL be the missing link?

Introduction South Asian immigrants (SAIs) in the US exhibit higher prevalence of coronary artery disease (CAD) and its risk factors compared with other ethnic populations. Conventional CAD risk factors do not explain the excess CAD risk; therefore there is a need to identify other markers that can predict future risk of CAD in high-risk SAIs. The objective of the current study is to assess the presence of sub-clinical CAD using common carotid artery intima-media thickness (CCA-IMT), and its association with metabolic syndrome (MS) and pro-inflammatory/dysfunctional HDL (Dys-HDL). Material and methods A community-based study was conducted on 130 first generation SAIs aged 35–65 years. Dys-HDL was determined using the HDL inflammatory index. Analysis was completed using logistic regression and Fishers exact test. Results Sub-clinical CAD using CCA-IMT ≥ 0.8 mm (as a surrogate marker) was seen in 31.46%. Age and gender adjusted CCA-IMT was significantly associated with type 2 diabetes (p = 0.008), hypertension (p = 0.012), high-sensitivity C-reactive protein (p < 0.001) and homocysteine (p = 0.051). Both the presence of MS and Dys-HDL was significantly correlated with CCA-IMT, even after age and gender adjustment. The odds of having Dys-HDL with CCA-IMT were 5 times (95% CI: 1.68, 10.78). Conclusions There is a need to explore and understand non-traditional CAD risk factors with a special focus on Dys-HDL, knowing that SAIs have low HDL levels. This information will not only help to stratify high-risk asymptomatic SAI groups, but will also be useful from a disease management point of view.

The long-term burden of severe sepsis and septic shock: Sepsis recidivism and organ dysfunction.

BACKGROUND Severe sepsis and septic shock mortality has improved; however, rates of persistent (28–90 days) and long-term (>90 day) organ dysfunction in sepsis survivors are unknown. METHODS Secondary analysis of a prospective cohort of adult emergency department patients with severe sepsis. RESULTS Of 110 sepsis admissions, we obtained follow-up on 51 of 78 survivors of whom 41% (21 of 51) had persistent organ dysfunction: pulmonary, 18% (9 of 51); renal, 22% (11 of 51); coagulopathy, 10% (5 of 51); cardiovascular, 6% (3 of 51); hepatic, 2% (1 of 51); and neurologic, 3% (3 of 51). We obtained follow-up on 40 of 73 survivors at more than 90 days of whom 38% (15 of 40) had long-term organ dysfunction: pulmonary, 13% (5 of 40); renal, 18% (7 of 40); coagulopathy, 3% (1 of 40); cardiovascular, 5% (2 of 40); hepatic, 0%; and neurologic, 5% (2 of 40). Readmission rate within 90 days was 32% (25 of 78), and recurrent sepsis was the cause of readmission in 52% (13 of 25). Baseline SOFA scores from the index sepsis admission were compared using Wilcoxon rank-sum test and were significantly different in participants with organ dysfunction versus those without organ dysfunction at less than 90 days (z, −2.51; p = 0.01). CONCLUSION Readmission with recurrent sepsis and organ dysfunction occurs frequently in sepsis survivors. Baseline SOFA score may be predictive of sepsis recidivism and persistent or recurrent organ dysfunction. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level IV.

Carotid intima media thickness and low HDL in South Asian immigrants: could dysfunctional HDL be the missing link?

Introduction South Asian immigrants (SAIs) in the US exhibit higher prevalence of coronary artery disease (CAD) and its risk factors compared with other ethnic populations. Conventional CAD risk factors do not explain the excess CAD risk; therefore there is a need to identify other markers that can predict future risk of CAD in high-risk SAIs. The objective of the current study is to assess the presence of sub-clinical CAD using common carotid artery intima-media thickness (CCA-IMT), and its association with metabolic syndrome (MS) and pro-inflammatory/dysfunctional HDL (Dys-HDL). Material and methods A community-based study was conducted on 130 first generation SAIs aged 35–65 years. Dys-HDL was determined using the HDL inflammatory index. Analysis was completed using logistic regression and Fishers exact test. Results Sub-clinical CAD using CCA-IMT ≥ 0.8 mm (as a surrogate marker) was seen in 31.46%. Age and gender adjusted CCA-IMT was significantly associated with type 2 diabetes (p = 0.008), hypertension (p = 0.012), high-sensitivity C-reactive protein (p < 0.001) and homocysteine (p = 0.051). Both the presence of MS and Dys-HDL was significantly correlated with CCA-IMT, even after age and gender adjustment. The odds of having Dys-HDL with CCA-IMT were 5 times (95% CI: 1.68, 10.78). Conclusions There is a need to explore and understand non-traditional CAD risk factors with a special focus on Dys-HDL, knowing that SAIs have low HDL levels. This information will not only help to stratify high-risk asymptomatic SAI groups, but will also be useful from a disease management point of view.

Apo lipoprotein A1 gene polymorphisms predict cardio-metabolic risk in South Asian immigrants

Objectives: Coronary artery disease (CAD) is a leading cause of death globally with increasing burden in South Asians in the US. Specific genetic variants that influence CAD have not been fully assessed in South Asian Immigrants. The goal is to identify Apo lipoprotein A1 (APOA1) gene polymorphisms and their association with CAD risk factors, metabolic syndrome and dysfunctional HDL (Dys-HDL). Methods: A community-based study on South Asians aged 35-65 years without CAD was conducted. APOA1 gene sequencing was performed and genotypes compared with cardiovascular findings. Results: The prevalence of metabolic syndrome and dysfunctional-HDL was 29.7% and 26%, respectively. Six novel APOA1 gene single nucleotide peptides (SNPs) were analyzed. Three of the six SNPs (G2, G3, and G5) were found to be associated with metabolic syndrome; G2 (T655C) (p=0.044), G3 (T756C) (p=0.037) and G5 (T1001C) (p=0.037). APOA1 gene SNP G1 (T319C) was highly correlated with low HDL levels (p=0.001). In our study, both associations of APOA1 SNPs with metabolic syndrome and low HDL remained after age-adjustment. Conclusion: Discovery of novel gene polymorphisms will help to understand further the causes of excess CAD risk in South Asians so that preventative strategies targeted to high-risk group can be developed.

Can novel Apo A-I polymorphisms be responsible for low HDL in South Asian immigrants?

Coronary artery disease (CAD) is the leading cause of death in the world. Even though its rates have decreased worldwide over the past 30 years, event rates are still high in South Asians. South Asians are known to have low high-density lipoprotein (HDL) levels. The objective of this study was to identify Apolipoprotein A-I (Apo A-I) polymorphisms, the main protein component of HDL and explore its association with low HDL levels in South Asians. A pilot study on 30 South Asians was conducted and 12-h fasting samples for C-reactive protein, total cholesterol, HDL, low-density lipoprotein (LDL), triglycerides, Lipoprotein (a), Insulin, glucose levels, DNA extraction, and sequencing of Apo A-I gene were done. DNA sequencing revealed six novel Apo A-I single nucleotide polymorphisms (SNPs) in South Asians, one of which (rs 35293760, C938T) was significantly associated with low (<40 mg/dl) HDL levels (P = 0.004). The association was also seen with total cholesterol (P = 0.026) and LDL levels (P = 0.032). This pilot work has highlighted some of the gene-environment associations that could be responsible for low HDL and may be excess CAD in South Asians. Further larger studies are required to explore and uncover these associations that could be responsible for excess CAD risk in South Asians.

The relationship of intravenous fluid chloride content to kidney function in patients with severe sepsis or septic shock

BACKGROUND Previous studies suggest a relationship between chloride-rich intravenous fluids and acute kidney injury in critically ill patients. OBJECTIVES The aim of this study was to evaluate the relationship of intravenous fluid chloride content to kidney function in patients with severe sepsis or septic shock. METHODS A retrospective chart review was performed to determine (1) quantity and type of bolus intravenous fluids, (2) serum creatinine (Cr) at presentation and upon discharge, and (3) need for emergent hemodialysis (HD) or renal replacement therapy (RRT). Linear regression was used for continuous outcomes, and logistic regression was used for binary outcomes and results were controlled for initial Cr. The primary outcome was change in Cr from admission to discharge. Secondary outcomes were need for HD/RRT, length of stay (LOS), mortality, and organ dysfunction. RESULTS There were 95 patients included in the final analysis; 48% (46) of patients presented with acute kidney injury, 8% (8) required first-time HD or RRT, 61% (58) were culture positive, 55% (52) were in shock, and overall mortality was 20% (19). There was no significant relationship between quantity of chloride administered in the first 24 hours with change in Cr (β = -0.0001, t = -0.86, R(2) = 0.92, P = .39), need for HD or RRT (odds ratio [OR] = 0.999; 95% confidence interval [CI], 0.999-1.000; P = .77), LOS >14 days (OR = 1.000; 95% CI, 0.999-1.000; P = .68), mortality (OR = 0.999; 95% CI, 0.999-1.000; P = .88), or any type of organ dysfunction. CONCLUSION Chloride administered in the first 24 hours did not influence kidney function in this cohort with severe sepsis or septic shock.

APOA1 gene polymorphisms in the South Asian immigrant population in the United States.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of death in the United States. South Asian immigrants (SAIs) from the Indian subcontinent living in the US are disproportionately at higher risk of CAD than other immigrant populations. Unique genetic factors may predispose SAIs to increased risk of developing CAD when adopting a Western lifestyle including a higher-fat diet, more sedentary behavior and additional gene-environment interactions. SAIs are known to have low levels of the protective high density lipoprotein (HDL) and an altered function for Apo-lipoprotein A-1 (ApoA1), the main protein component of HDL cholesterol. One gene that may be genetically distinctive in this population is APOA1 which codes for ApoA-1 protein, a potentially important contributing factor in the development of CAD. MATERIALS AND METHODS: DNA sequencing was performed to determine the status of the seven single-nucleotide polymorphisms (SNPs) in the APOA1 gene from 94 unrelated SAI adults. Genotypes, allelic frequencies, and intragenic linkage disequilibrium of the APOA1 SNPs were calculated. RESULTS: Several polymorphisms and patterns were common among persons of south Asian ethnicity. Frequencies for SNPs T655C, T756C and T1001C were found to be different than those reported in European Caucasian individuals. Linkage disequilibrium was found to be present between most (13 of 15) SNP pairings indicating common inheritance patterns. CONCLUSIONS: SAIs showed variability in the sequence of the APOA1 gene and linkage disequilibrium for most SNPS. This pattern of APOA1 SNPs may contribute to decreased levels of HDL cholesterol reported in SAIs, leading to an increased risk for developing CAD in this population.

Assessing the Impact of Health Literacy on Education Retention of Stroke Patients

Introduction Inadequate health literacy is a pervasive problem with major implications for reduced health status and health disparities. Despite the role of focused education in both primary and secondary prevention of stroke, the effect of health literacy on stroke education retention has not been reported. We examined the relationship of health literacy to the retention of knowledge after recommended stroke education. Methods This prospective cross-sectional study was conducted at an urban safety-net hospital. Study subjects were patients older than 18 admitted to the hospital stroke unit with a diagnosis of acute ischemic stroke who were able to provide informed consent to participate (N = 100). Health literacy levels were measured by using the short form of Test of Functional Health Literacy in Adults. Patient education was provided to patients at an inpatient stroke unit by using standardized protocols, in compliance with Joint Commission specifications. The education outcomes for poststroke care education, knowledge retention, was assessed for each subject. The effect of health literacy on the Stroke Patient Education Retention scores was assessed by using univariate and multivariate analyses. Results Of the 100 participating patients, 59% had inadequate to marginal health literacy. Stroke patients who had marginal health literacy (mean score, 7.45; standard deviation [SD], 1.9) or adequate health literacy (mean score, 7.31; SD, 1.76) had statistically higher education outcome scores than those identified as having inadequate health literacy (mean score, 5.58; SD, 2.06). Results from multivariate analysis indicated that adequate health literacy was most predictive of education outcome retention. Conclusions This study demonstrated a clear relationship between health literacy and stroke education outcomes. Studies are needed to better understand the relationship of health literacy to key educational outcomes for primary or secondary prevention of stroke and to refine stroke education for literacy levels of high-risk populations.

Coronary Artery Diseases in South Asian Immigrants: An Update on High Density Lipoprotein Role in Disease Prevention

Over the past several years, the overall prevalence and incidence of cardiovascular diseases (CVD) including coronary artery diseases (CAD) have declined in the United States (US) and in many developed countries. However, among South Asian in general and South Asian immigrants (SAIs) in particular, a disturbing trend toward high rates of CAD has been noted. This trend is associated with a high prevalence of conventional risk factors and metabolic syndrome in this population, yet these conventional risk factors may not account for the greater CAD risk among SAIs. A search for additional markers is warranted, to enable early detection and prevention of CAD in this high risk group. High density lipoprotein (HDL) is one of the predictor of CAD and is considered to be cardio-protective. However, some of the recent studies have shown that HDL is not only ineffective as an antioxidant but, paradoxically, appears to be pro-oxidant, and has been found to be associated with CAD. Such HDL is called dysfunctional HDL. We present here an overview CAD and CAD risk factors in general and dyslipidemias in particular in SAIs. In addition, the evolving theories on dysfunctional HDL and its impact on CAD are also briefly presented.