Browsing by Subject "Cholesterol"
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Item Open Access Birth Cohort, Age, and Sex Strongly Modulate Effects of Lipid Risk Alleles Identified in Genome-Wide Association Studies.(PLoS One, 2015) Kulminski, Alexander M; Culminskaya, Irina; Arbeev, Konstantin G; Arbeeva, Liubov; Ukraintseva, Svetlana V; Stallard, Eric; Wu, Deqing; Yashin, Anatoliy IInsights into genetic origin of diseases and related traits could substantially impact strategies for improving human health. The results of genome-wide association studies (GWAS) are often positioned as discoveries of unconditional risk alleles of complex health traits. We re-analyzed the associations of single nucleotide polymorphisms (SNPs) associated with total cholesterol (TC) in a large-scale GWAS meta-analysis. We focused on three generations of genotyped participants of the Framingham Heart Study (FHS). We show that the effects of all ten directly-genotyped SNPs were clustered in different FHS generations and/or birth cohorts in a sex-specific or sex-unspecific manner. The sample size and procedure-therapeutic issues play, at most, a minor role in this clustering. An important result was clustering of significant associations with the strongest effects in the youngest, or 3rd Generation, cohort. These results imply that an assumption of unconditional connections of these SNPs with TC is generally implausible and that a demographic perspective can substantially improve GWAS efficiency. The analyses of genetic effects in age-matched samples suggest a role of environmental and age-related mechanisms in the associations of different SNPs with TC. Analysis of the literature supports systemic roles for genes for these SNPs beyond those related to lipid metabolism. Our analyses reveal strong antagonistic effects of rs2479409 (the PCSK9 gene) that cautions strategies aimed at targeting this gene in the next generation of lipid drugs. Our results suggest that standard GWAS strategies need to be advanced in order to appropriately address the problem of genetic susceptibility to complex traits that is imperative for translation to health care.Item Open Access Health beliefs and desire to improve cholesterol levels among patients with hyperlipidemia.(Patient education and counseling, 2016-05) Zullig, Leah L; Sanders, Linda L; Thomas, Steven; Brown, Jamie N; Danus, Susanne; McCant, Felicia; Bosworth, Hayden BObjective
Because hyperlipidemia is asymptomatic, many veterans affairs (VA) patients may not perceive it seriously. We assessed key Health Belief model concepts to describe patients' cholesterol-related health beliefs and examine associations between patient-level factors and desire to improve cholesterol control.Methods
We used baseline data from an ongoing randomized clinical trial. Eligible patients were receiving care at the Durham VA and had CVD risk-total cholesterol levels >130 mg/dL and/or <80% medication adherence in the previous 12 months. A survey assessed patients' health beliefs about high cholesterol and self-reported medication adherence. Multivariable logistic regression examined whether there was an association between desire to control cholesterol and cholesterol status.Results
Approximately 64% (n=155) of patients perceived high cholesterol as 'very serious'. In multivariable logistic regression analysis, patients who perceived high cholesterol as 'very serious' (OR 2. 26, p=0.032) and/or with high self-efficacy (OR 4.70, p<0.001) had increased odds of desiring cholesterol control.Conclusion
The factors most significantly associated with desire to improve cholesterol control were perceiving hyperlipidemia as 'very serious and self-efficacy for cholesterol control.Practice implication
Educating patients, with the goal of appropriately increasing their perceived risk of disease, is likely necessary to impact cholesterol control.Item Open Access HIV and Hepatitis C-Coinfected Patients Have Lower Low-Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent "PCSK9-Lipid Paradox".(Journal of the American Heart Association, 2016-04) Kohli, Payal; Ganz, Peter; Ma, Yifei; Scherzer, Rebecca; Hur, Sophia; Weigel, Bernard; Grunfeld, Carl; Deeks, Steven; Wasserman, Scott; Scott, Rob; Hsue, Priscilla YBackground
Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and improve outcomes in the general population. HIV-infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus (HCV) coinfection, making PCSK9 inhibition a potentially attractive therapy.Methods and results
We studied 567 participants from a clinic-based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL-C level was 100 mg/dL (IQR 77-124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol, LDL-C, and high-density lipoprotein cholesterol levels were lower in coinfected patients compared with controls (P<0.001). PCSK9 was 21% higher in HIV/HCV-coinfected patients versus controls (95% CI 9-34%, P<0.001) and 11% higher in coinfected individuals versus those with HIV infection alone (95% CI 3-20%, P=0.008). After adjustment for cardiovascular risk factors, HIV/HCV coinfection remained significantly associated with 20% higher PCSK9 levels versus controls (95% CI 8-33%, P=0.001). Interleukin-6 levels increased in a stepwise fashion from controls (lowest) to HIV-infected to HIV/HCV-coinfected individuals (highest) and correlated with PCSK9 (r=0.11, P=0.018).Conclusions
Despite having lower LDL-C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin-6. Clinical trials should be conducted to determine the efficacy of targeted PCSK9 inhibition in the setting of HIV/HCV coinfection.Item Open Access Human Genetic Variation in VAC14 Regulates Pathogen Entry and Risk of Infectious Disease(2017) Alvarez, Monica IsabelHuman genetic variation can be leveraged to understand the subtleties of how common variants with small effect sizes can alter cellular phenotypes and ultimately affect susceptibility to pathogenic disease. By combining GWAS of different phenotypic scales and basic cell biology, we can answer how a particular SNP affects a disease. This body of work elucidates the biological mechanism of how a SNP in VAC14, which encodes a human scaffolding protein involved in phosphoinositide metabolism, alters susceptibility to Typhoid Fever and other pathogens.
Using Hi-HOST (High-throughput Human in vitro Susceptibility Testing), a GWAS platform for cellular host-pathogen traits, we discovered that the ‘A’ allele of rs8060947 was associated with decreased VAC14 protein expression and increased Salmonella Typhi invasion. We experimentally confirmed the phenotype using RNAi to transiently decrease VAC14 protein expression in LCLs and Helas and saw increased Salmonella Typhi invasion. Further studies, using genetic and pharmacological manipulations were able to determine how VAC14 affects Salmonella Typhi invasion. CRISPR knockout VAC14 cells had a robust increase in invasion, and had increased cholesterol accumulation in the cell. Salmonella preferentially docks to cholesterol on the host plasma membrane as one of the first steps involved in invasion. Thus, increasing cholesterol at the plasma membrane increased the number of docked bacteria and ultimately caused higher invasion percentages.
To confirm the relevance of cholesterol and Salmonella Typhi beyond cell culture, we infected the swim bladder of Zebrafish with S. Typhi. Fish were pretreated with Ezetimibe, an FDA approved cholesterol-reducing drug, and then subsequently infected with S. Typhi. Fish treated with Ezetimibe, had decreased cholesterol staining by filipin, and had increased survival from S. Typhi infections. Additionally, because of the optically transparent nature of the zebrafish embryo we were able to image the fish 24hrs after infection and show that ezetimibe treated fish had higher bacterial clearance.
In addition to the fish studies, a collaboration with Dr. Sarah Dunstan (University of Melbourne) was able to retrospectively determine that VAC14 had an effect on human susceptibility to typhoid fever. The ‘A’ allele for SNP rs8060947, which we showed had decreased VAC14 protein expression and increased S. Typhi invasion in cell culture, was found to be more common in people with typhoid fever, suggesting the ‘A’ allele increases human susceptibility to this disease. All together, we have shown that decreased VAC14 expression causes an increase in cellular cholesterol, leading to an increase in docking and invasion of Salmonella and ultimately increasing your chances of acquiring typhoid fever.
The central role of cholesterol in entry of multiple pathogens led us to hypothesize that natural variation or experimental manipulation of VAC14 expression could play a role in pathogens beyond Salmonella. Here we show that its effects extend beyond bacteria to parasites. With cholesterol regulating entry of Plasmodium into hepatocytes, we hypothesized that increasing the amount of cellular cholesterol in hepatocytes will increase Plasmodium entry. These ideas are being tested in collaboration with Maria Toro and Dr. Emily Derbyshire (Duke University). However, unpublished human genetic data already support the idea that VAC14 regulates susceptibility to malaria infection. The same SNP associated with Salmonella invasion (rs8060947) is associated with malaria risk in African populations (Gavin Band and the MalariaGEN Consortium, personal communication).
VAC14 may also affect pathogen entry through its role in regulation of endosomal trafficking. VAC14 forms a complex with the FIG4 phosphatase and PIKfyve kinase to modulate endosomal trafficking through the metabolism of PtdIns(3,5)P2. Recently, FIG4 and PIKfyve were found to be necessary for Ebola entry in a somatic cell genetic screen. Using our VAC14 CRISPR knockout cells we determined that cells mutated for VAC14 had a similar phenotype. Ebola virus-like-particle (VLP) entry decreased dramatically in cells lacking VAC14. While we discovered that VAC14 affects cellular cholesterol, its main reported function is to regulate endosomal trafficking. We hypothesize that lack of VAC14 interferes with proper endosomal maturation and thus prevents the Ebola VLP from reaching its intracellular receptor NPC1 and exiting into the cytoplasm.
The common allele (A) that alters VAC14 expression is associated with decreased protein synthesis, and increased susceptibility to both Salmonella and Malaria infection. On the other hand, decreased VAC14 expression inhibits proper endolysosomal trafficking, inhibiting Ebola infection. These two mechanisms of affecting different infectious diseases may provide opposing forces in an example of balancing selection.
Item Open Access Infusion of Reconstituted High-Density Lipoprotein, CSL112, in Patients With Atherosclerosis: Safety and Pharmacokinetic Results From a Phase 2a Randomized Clinical Trial.(Journal of the American Heart Association, 2015-08-25) Tricoci, Pierluigi; D'Andrea, Denise M; Gurbel, Paul A; Yao, Zhenling; Cuchel, Marina; Winston, Brion; Schott, Robert; Weiss, Robert; Blazing, Michael A; Cannon, Louis; Bailey, Alison; Angiolillo, Dominick J; Gille, Andreas; Shear, Charles L; Wright, Samuel D; Alexander, John HBackground
CSL112 is a new formulation of human apolipoprotein A-I (apoA-I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double-blind, multicenter, dose-ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease.Methods and results
Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2-hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug-related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA-I plasma concentration and measures of the ability of serum to promote cholesterol efflux from cells ex vivo. Of 45 patients randomized, 7, 12, and 14 received 1.7-, 3.4-, and 6.8-g CSL112, respectively, and 11 received placebo. There were no clinically significant elevations (>3× upper limit of normal) in alanine aminotransferase or aspartate aminotransferase. Adverse events were nonserious and mild and occurred in 5 (71%), 5 (41%), and 6 (43%) patients in the CSL112 1.7-, 3.4-, and 6.8-g groups, respectively, compared with 3 (27%) placebo patients. The imbalance in adverse events was attributable to vessel puncture/infusion-site bruising. CSL112 resulted in rapid (T(max)≈2 hours) and dose-dependent increases in apoA-I (145% increase in the 6.8-g group) and total cholesterol efflux (up to 3.1-fold higher than placebo) (P<0.001).Conclusions
CSL112 infusion was well tolerated in patients with stable atherosclerotic disease. CSL112 immediately raised apoA-I levels and caused a rapid and marked increase in the capacity of serum to efflux cholesterol. This potential novel approach for the treatment of atherosclerosis warrants further investigation.Clinical trial registration
URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01499420.Item Open Access Mimicking effects of cholesterol in lipid bilayer membranes by self-assembled amphiphilic block copolymers.(Soft matter, 2023-07) Wang, Xiaoyuan; Xu, Shixin; Cohen, Fredric S; Zhang, Jiwei; Cai, YongqiangThe effect of cholesterol on biological membranes is important in biochemistry. In this study, a polymer system is used to simulate the consequences of varying cholesterol content in membranes. The system consists of an AB-diblock copolymer, a hydrophilic homopolymer hA, and a hydrophobic rigid homopolymer C, corresponding to phospholipid, water, and cholesterol, respectively. The effect of the C-polymer content on the membrane is studied within the framework of a self-consistent field model. The results show that the liquid-crystal behavior of B and C has a great influence on the chemical potential of cholesterol in bilayer membranes. The effects of the interaction strength between components, characterized by the Flory-Huggins parameters and the Maier-Saupe parameter, were studied. Some consequences of adding a coil headgroup to the C-rod are presented. Results of our model are compared to experimental findings for cholesterol-containing lipid bilayer membranes.Item Open Access Neuroprotection resulting from insufficiency of RANBP2 is associated with the modulation of protein and lipid homeostasis of functionally diverse but linked pathways in response to oxidative stress.(Dis Model Mech, 2010-09) Cho, Kyoung-in; Yi, Haiqing; Tserentsoodol, Nomingerel; Searle, Kelly; Ferreira, Paulo AOxidative stress is a deleterious stressor associated with a plethora of disease and aging manifestations, including neurodegenerative disorders, yet very few factors and mechanisms promoting the neuroprotection of photoreceptor and other neurons against oxidative stress are known. Insufficiency of RAN-binding protein-2 (RANBP2), a large, mosaic protein with pleiotropic functions, suppresses apoptosis of photoreceptor neurons upon aging and light-elicited oxidative stress, and promotes age-dependent tumorigenesis by mechanisms that are not well understood. Here we show that, by downregulating selective partners of RANBP2, such as RAN GTPase, UBC9 and ErbB-2 (HER2; Neu), and blunting the upregulation of a set of orphan nuclear receptors and the light-dependent accumulation of ubiquitylated substrates, light-elicited oxidative stress and Ranbp2 haploinsufficiency have a selective effect on protein homeostasis in the retina. Among the nuclear orphan receptors affected by insufficiency of RANBP2, we identified an isoform of COUP-TFI (Nr2f1) as the only receptor stably co-associating in vivo with RANBP2 and distinct isoforms of UBC9. Strikingly, most changes in proteostasis caused by insufficiency of RANBP2 in the retina are not observed in the supporting tissue, the retinal pigment epithelium (RPE). Instead, insufficiency of RANBP2 in the RPE prominently suppresses the light-dependent accumulation of lipophilic deposits, and it has divergent effects on the accumulation of free cholesterol and free fatty acids despite the genotype-independent increase of light-elicited oxidative stress in this tissue. Thus, the data indicate that insufficiency of RANBP2 results in the cell-type-dependent downregulation of protein and lipid homeostasis, acting on functionally interconnected pathways in response to oxidative stress. These results provide a rationale for the neuroprotection from light damage of photosensory neurons by RANBP2 insufficiency and for the identification of novel therapeutic targets and approaches promoting neuroprotection.Item Open Access Novel Methods of Mycobacterial Control via Manipulation of Host Lipid Bioavailability(2020) McClean, Colleen MichelleLipids represent an important source of nutrition for infecting mycobacteria, accumulating within the necrotic core of granulomas and present in foamy macrophages associated with mycobacterial infection. In order to better understand the timing, process and importance of lipid accumulation, we developed methods for direct in vivo visualization and quantification of lipid accumulation using the zebrafish-M. marinum model of infection. We find that neutral lipids accumulate cell autonomously in mycobacterium-infected macrophages in vivo during early infection, with detectable levels of accumulation by two days post-infection. Reducing available free cholesterol and neutral lipids during early infection via treatment with ezetimibe, an FDA-approved drug, resulted in a reduction of bacterial growth in vivo. The effect of ezetimibe in reducing bacterial growth was dependent on the mce4 operon, a key bacterial determinant of lipid utilization. Thus, in vivo, lipid accumulation can occur cell autonomously at early timepoints of mycobacterial infection, and this early lipid accumulation confers a growth advantage to infecting mycobacteria.
This accumulation represents a perturbation of the normal homeostatic mechanisms by which intracellular lipids are tightly controlled. Under homeostatic conditions macrophages are central to the function of returning excess lipids to the liver where they are processed for excretion via the digestive tract. This function of macrophages, termed reverse cholesterol transport, results from the uptake of excess extracellular lipids, followed by the coordinated efflux of these lipids through the transport proteins ABCA1 and ABCG1 and packaging into HDL particles containing ApoAI and ApoAII. This process is controlled via the action of nuclear receptors including PPARγ, PPAR-α, and LXRα.
We performed RNA-seq analysis of gene expression in macrophages both uninfected and infected with mycobacteria and observed a profound down-regulation of all the major lipoproteins. The HDL associated lipoproteins ApoAI and ApoAII were the most profoundly down regulated. Based on this observation we sought to investigate the role of nuclear receptors involved in intracellular lipid sensing and control of apolipoprotein expression. We determined that agonism and antagonism of LXRα signaling decrease and increase infection burden during in vivo studies respectively. We further found that the ApoAI agonizing fibrate drugs fenofibrate and gemfibrozil reduce mycobacterial infection in vivo. This work demonstrates that lipid lowering agents already approved for use in humans might function as relevant adjuvant therapies toward treatment of mycobacterial infections.
Item Open Access Plasma lipoproteins of free-ranging howling monkeys (Alouatta palliata).(Comp Biochem Physiol B, 1987) Clark, SB; Tercyak, AM; Glander, KE1. Plasma lipids and lipoproteins of free-ranging howling monkeys from Costa Rica (Alouatta palliata), aged 5 months to 23 years, were characterized. 2. High density lipoproteins were lipid-rich, similar to HDL2 of human plasma. 3. Fatty acid compositions of major lipid classes of very low, low and high density lipoproteins differed among social groups, possibly due to both dietary and genetic factors. 4. Low and high density lipoprotein phospholipids were enriched in phosphatidylethanolamine. 5. Howler plasma cross reacted with antihuman apoA-I antibodies but not with antihuman LDL antibodies. 6. No dimeric form of apoA-II was present, unlike human apoA-II.Item Open Access Rationale and design of a nurse-led intervention to extend the HIV treatment cascade for cardiovascular disease prevention trial (EXTRA-CVD).(American heart journal, 2019-10) Okeke, Nwora Lance; Webel, Allison R; Bosworth, Hayden B; Aifah, Angela; Bloomfield, Gerald S; Choi, Emily W; Gonzales, Sarah; Hale, Sarah; Hileman, Corrilynn O; Lopez-Kidwell, Virginie; Muiruri, Charles; Oakes, Megan; Schexnayder, Julie; Smith, Valerie; Vedanthan, Rajesh; Longenecker, Chris TPersons living with human immunodeficiency virus (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD). In spite of this, uptake of evidence-based clinical interventions for ASCVD risk reduction in the HIV clinic setting is sub-optimal. METHODS: EXTRA-CVD is a 12-month randomized clinical effectiveness trial that will assess the efficacy of a multi-component nurse-led intervention in reducing ASCVD risk among PLHIV. Three hundred high ASCVD risk PLHIV across three sites will be randomized 1:1 to usual care with generic prevention education or the study intervention. The study intervention will consist of four evidence-based components: (1) nurse-led care coordination, (2) nurse-managed medication protocols and adherence support (3) home BP monitoring, and (4) electronic health records support tools. The primary outcome will be change in systolic blood pressure and secondary outcome will be change in non-HDL cholesterol over the course of the intervention. Tertiary outcomes will include change in the proportion of participants in the following extended cascade categories: (1) appropriately diagnosed with hypertension and hyperlipidemia (2) appropriately managed; (3) at treatment goal (systolic blood pressure <130 mm Hg and non-HDL cholesterol < National Lipid Association targets). CONCLUSIONS: The EXTRA-CVD trial will provide evidence appraising the potential impact of nurse-led interventions in reducing ASCVD risk among PLHIV, an essential extension of the HIV care continuum beyond HIV viral suppression.Item Open Access Regulation of Cartilage Tumors by Mutations in Isocitrate Dehydrogenases(2021) Zhang, HongyuanEnchondroma and chondrosarcoma are common benign and malignant cartilaginous neoplasms. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are present in the majority of these tumors. Mutant IDH enzymes gain a neomorphic function of producing D-2-hydroxyglutarate (D-2HG) from ?-ketoglutarate. Expression of a mutant Idh1 gene is sufficient for enchondroma initiation but inhibiting mutant IDH enzymes did not cause a consistent change in the tumorigenic properties of chondrosarcomas. It is unclear how mutations of isocitrate dehydrogenases regulate cartilage tumors from initiation to cancer progression and maintenance. I hypothesize that mutations in IDH enzymes could regulate cartilage tumors through changes in gene expression and cellular metabolism. To address these questions, I examined the transcriptional regulation and metabolic regulations of mutant isocitrate dehydrogenases in chondrocytes and chondrosarcomas and identified cholesterol biosynthesis and glutamine metabolism as two key pathways dictating tumor behavior.
To understand the transcriptional regulation of IDH1 mutation in cartilage tumors, I performed RNA-sequencing analysis in chondrocytes from Col2a1Cre;Idh1LSL/+ mutant animals and their littermate wildtype controls and identified that cholesterol biosynthesis pathway was upregulated. Genetic inhibition of cholesterol biosynthesis in an enchondroma mouse model and pharmacological inhibition of cholesterol biosynthesis in human patient chondrosarcoma samples suppressed tumor development in vivo. Taken together, these data suggest that intracellular cholesterol synthesis is a potential therapeutic target for enchondromas and chondrosarcomas.
From a metabolic perspective, I found that chondrocytes and chondrosarcomas with mutations in IDH1/2 genes had enhanced glutamine utilization for downstream metabolism. Using genetic and pharmacological approaches, I demonstrated that glutaminase-mediated glutamine metabolism played distinct roles in enchondromas and chondrosarcomas with IDH1/2 mutations. Genetic ablation of glutaminase in chondrocytes with Idh1 mutation increased the number and size of enchondroma-like lesions. Pharmacological inhibition of glutaminase led to decreased tumor weight of chondrosarcoma xenograft. During enchondroma development, glutamine-derived -ketoglutarate plays important roles in regulating chondrocyte differentiation and proliferation. In chondrosarcoma, glutamine-derived non-essential amino acids are important in preventing cell apoptosis.
In summary, findings in this dissertation described transcriptional and metabolic regulations by mutations in isocitrate dehydrogenases in cartilage tumors enchondroma and chondrosarcoma and provide novel insights for developing therapies for these diseases.
Item Open Access Self-reported medication nonadherence predicts cholesterol levels over time.(Journal of psychosomatic research, 2019-03) Blalock, Dan V; Zullig, Leah L; Bosworth, Hayden B; Taylor, Shannon S; Voils, Corrine IObjective
Self-report measures of medication nonadherence are frequently adapted to new clinical populations without evidence of validity. We evaluated the predictive validity of a medication nonadherence measure previously validated in patients with hypertension among patients taking cholesterol-reducing medications.Method
This secondary analysis involves data from a randomized trial (VA HSR&D IIR 08-297) conducted at the Durham Veterans Affairs Medical Center. At baseline, 6-months, and 12-months, serum cholesterol was obtained and participants (n = 236) completed a 3-item measure of extent of nonadherence to cholesterol-reducing medications. Two cross-lagged panel models with covariates, in addition to growth curve analysis, were used to examine the predictive utility of self-reported nonadherence on concurrent and future cholesterol levels, while accounting for potential reverse-causation.Results
Extent of nonadherence items produced reliable scores across time and fit a single-factor model (CFI = 0.99). Nonadherence, and changes in nonadherence, moderately predicted future cholesterol values, and changes in cholesterol values (7 of 9 longitudinal associations were significant at p < .05; B's ranged from 0.16 to 0.35). Evidence for reverse associations was weaker (3 of 9 longitudinal associations were significant at p < .05; B's ranged from 0.16 to 0.36).Conclusion
Analyses support the predictive validity of this medication nonadherence measure over the competing reverse-causation hypothesis.Item Open Access The Cholesterol, Hypertension, And Glucose Education (CHANGE) study: results from a randomized controlled trial in African Americans with diabetes.(American heart journal, 2013-07) Crowley, Matthew J; Powers, Benjamin J; Olsen, Maren K; Grubber, Janet M; Koropchak, Celine; Rose, Cynthia M; Gentry, Pamela; Bowlby, Lynn; Trujillo, Gloria; Maciejewski, Matthew L; Bosworth, Hayden BBackground
Cardiovascular disease (CVD) and diabetes account for one-third of the mortality difference between African American and white patients. We evaluated the effect of a CVD risk reduction intervention in African Americans with diabetes.Methods
We randomized 359 African Americans with type 2 diabetes to receive usual care or a nurse telephone intervention. The 12-month intervention provided monthly self-management support and quarterly medication management facilitation. Coprimary outcomes were changes in systolic blood pressure (SBP), hemoglobin A1c (HbA1c), and low-density lipoprotein cholesterol (LDL-C) over 12 months. We estimated between-intervention group differences over time using linear mixed-effects models. The secondary outcome was self-reported medication adherence.Results
The sample was 72% female; 49% had low health literacy, and 37% had annual income <$10,000. Model-based estimates for mean baseline SBP, HbA1c, and LDL-C were 136.8 mm Hg (95% CI 135.0-138.6), 8.0% (95% CI 7.8-8.2), and 99.1 mg/dL (95% CI 94.7-103.5), respectively. Intervention patients received 9.9 (SD 3.0) intervention calls on average. Primary providers replied to 76% of nurse medication management facilitation contacts, 18% of these resulted in medication changes. There were no between-group differences over time for SBP (P = .11), HbA1c (P = .66), or LDL-C (P = .79). Intervention patients were more likely than those receiving usual care to report improved medication adherence (odds ratio 4.4, 95% CI 1.8-10.6, P = .0008), but adherent patients did not exhibit relative improvement in primary outcomes.Conclusions
This intervention improved self-reported medication adherence but not CVD risk factor control among African Americans with diabetes. Further research is needed to determine how to maximally impact CVD risk factors in African American patients.