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1.  Effects of Low-Dose Aspirin and Fish Oil on Platelet Function and NF-kappaB in Adults with Diabetes Mellitus 
Many diabetics are insensitive to aspirin’s platelet anti-aggregation effects. The possible modulating effects of coadministration of aspirin and fish oil in subjects with diabetes are poorly characterized.
Participants and Methods
Thirty adults with type 2 diabetes mellitus were treated with aspirin 81 mg/d for 7 days, then with fish oil 4g/day for 28 days, then the combination of fish oil and aspirin for another 7 days.
Aspirin alone and in combination with fish oil reduced platelet aggregation in most participants. Five of 7 participants classified as aspirin insensitive 1 week after daily aspirin ingestion were sensitive after the combination. Although some platelet aggregation measures correlated positively after aspirin and fish oil ingestion alone and (in combination) in all individuals, correlation was only observed in those who were aspirin insensitive after ingestion of the combination.
Co-adminstration of aspirin and fish oil may reduce platelet aggregation more than aspirin alone in adults with diabetes mellitus.
PMCID: PMC3683095  PMID: 23664596
Omega-3 fatty acids; eicosapentaenoic acid; docosahexaenoic acid; aspirin; acetylsalicylic acid; platelet function; NF-kappaB; nuclear factor kappa-light-chain-enhancer of activated B cells
2.  Risk of cardiovascular disease in HIV, Hepatitis C, or HIV/Hepatitis C patients compared to the general population 
Due to effective antiretroviral therapy HIV patients are living longer, and their risk of cardiovascular disease (CVD) is a growing concern. It is unknown whether co-infection with hepatitis C (HCV) changes an HIV person’s CVD risk, and how the risks compare to the general population. The objective of this study was to compare the Framingham Risk Score (FRS) and vascular age differences in persons with HIV, HCV or HIV/HCV disease to the general population.
HIV, HCV and HIV/HCV patients with clinic visits between 2004–2009 were sampled from medical clinics in Rochester, NY. Uninfected persons were randomly selected from the National Health and Nutrition Examination Survey (NHANES) and individually matched on sex, race, and age. We stratified by infection group and conducted separate multivariable linear regression between each infection group and the sex, race, and age matched participants from NHANES.
Rochester patients (HIV=239, HCV=167, HIV/HCV=182) were compared 3:1 to the NHANES participants. After controlling for weight, marital status, current pharmacotherapies, and the matching variables of sex, race and age, HIV/HCV patients had a 2% higher general FRS compared to the general population (p=0.03) and vascular age differences that were 4.1 years greater (p=.01). HCV patients had a 2.4% higher general FRS than the general population (p<.001), and vascular age differences that were 4.4 years greater (p<.001). CVD risk was elevated, but not significantly different between HIV patients and the general population.
CVD risk is elevated among HIV/HCV and HCV infected persons compared to the general population.
PMCID: PMC3533243  PMID: 23241046
HIV; Hepatitis C; HIV/HCV co-infection; cardiovascular disease risk; Framingham Risk Score
3.  Short Communication: Risk of Elevated Total Cholesterol/High-Density Lipoprotein Cholesterol Ratio After Antiretroviral Therapy in HIV/Hepatitis C Virus Patients 
AIDS Research and Human Retroviruses  2012;28(12):1552-1556.
Dyslipidemia from highly active antiretroviral therapy (HAART) use has been reported to be less severe among persons with HIV and hepatitis C (HCV) compared to those with HIV monoinfection. However, the effect on lipoprotein ratios is less clear. The total cholesterol/high-density lipoprotein ratio (TC/HDL-C ratio) is a robust measure of cardiovascular disease (CVD) risk but has not been examined in the context of HIV/HCV-coinfected patients. We compared the TC/HDL-C ratio before HAART initiation and after at least 6 months on HAART between patients monoinfected with HIV and coinfected with HIV and HCV. Pre- and post-HAART TC, HDL-C, and non-HDL-C were also assessed. Although TC, HDL-C, and non-HDL-C significantly increased after HAART initiation in both HIV and HIV/HCV patients, the TC/HDL-C ratio did not. In addition, although the pre- and post-HAART TC, HDL-C, non-HDL-C, and TC/HDL-C ratio were significantly different between HIV and HIV/HCV patients, the magnitude in the change from pre- to post-HAART was not significantly different between infection groups. These results persisted after controlling for age, sex, race, current pharmacotherapy for lipoproteins, body mass index, and current CD4 cell count. The magnitude of change in the TC/HDL-C ratio after HAART initiation is not significantly different between HIV and HIV/HCV patients, suggesting subsequent CVD risk in HIV/HCV patients may be greater than currently appreciated.
PMCID: PMC3505066  PMID: 22380598
4.  The combination of EPA+DHA and low-dose aspirin ingestion reduces platelet function acutely whereas each alone may not in healthy humans 
Aspirin’s effectiveness in reducing cardiovascular disease events is inadequate in some individuals, a phenomenon termed aspirin “resistance”. The hypothesis that combining low dose aspirin with eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA) reduces platelet function in the acute setting has not been investigated.
Patients and methods
We conducted a clinical trial of EPA+DHA and aspirin ingestion in healthy adults. Fasting blood samples were drawn at baseline and 4 h after supplementation with EPA/DHA (3.4 g/d), aspirin (81 mg), and both. Platelet function was measured using the Platelet Function Analyzer-100 (PFA-100). Plasma lysophosphatidylcholine (LPC), lysophosphatidic acid (LPA), autotaxin, angiogenesis activators, and cytokines were measured.
Platelet function decreased with the combination of aspirin+EPA/DHA (p=0.03) but not with either alone (p>0.05). EPA-LPC increased (p=0.002).
Discussion and conclusions
Our results demonstrate that a potentially beneficial effect on platelet function occurred within 4 h after ingestion of low-dose aspirin and EPA+DHA in healthy adults.
PMCID: PMC3589139  PMID: 23017325
Omega-3 fatty acids; Eicosapentaenoic acid; Docosahexaenoic acid; Aspirin; Acetylsalicylic acid; Platelet function; Platelet function analyzer-100
5.  Integrating the Chronic Care Model into a Novel Medical Student Course 
Health education journal  2011;70(1):39-47.
To determine if integration of the Chronic Care Model into undergraduate medical education is associated with anticipated use of the Model and if student perceptions match actual integration of the Model into their community projects.
This was a cross-sectional study using qualitative and quantitative data.
A novel fourth-year medical student community health improvement course.
The study included 45 students who had enrolled in the course before introduction of the Model and 32 formally introduced to the Model through a lecture. Perceptions were measured through a survey and a focus group with data analyzed amongst and between cohorts. Projects were reviewed for actual integration of Model elements and these data were compared with reported student perceptions.
Although they were in general utilizing most elements of the Model, student perceptions of their use of Model elements significantly differed from actual use of particular elements (p<0.001). For instance, whereas the majority believed that their projects focused on the element of Community Resources, most projects actually focused on Self-Management Support. Students formally introduced to the Model trended toward the belief that it would enhance their ability to care for patients more than students without formal exposure to it (p=0.0516).
Although medical students may not recognize it, they may already focus their actions and thinking regarding health improvement toward patient self-management of their chronic disease. Although students require education and training if the Model is to be widely used, they may be naturally attracted to it.
PMCID: PMC3083078  PMID: 21532935
6.  Associations between omega-3 poly-unsaturated fatty acids from fish consumption and severity of depressive symptoms: an analysis of the 2005–2008 National Health and Nutrition Examination Survey 
Fish is the primary source of dietary omega-3 poly-unsaturated fatty acids EPA and DHA, which have been reported to reduce depressive symptoms in clinical trials. We assessed the association between fish consumption and depressive symptoms in a nationally representative sample of 10,480 adults from the 2005–2008 National Health and Nutrition Examination Survey. Depressive symptoms were classified by severity using the Patient Health Questionnaire. Fish meal consumption reported in 30-day food frequency questionnaires, and EPA+DHA intake computed from 24-hour dietary recalls were evaluated in relation to depressive symptoms using multivariable ordinal logistic regression. Consumption of breaded fish showed an increased risk of greater depressive symptom severity, while all fish, non-breaded fish, and shell fish were not associated. Any EPA+DHA intake was significantly associated with fewer depressive symptoms. Exposure-response analyses revealed no clear patterns for any intake measures. Inconsistent patterns of associations in our study may be partially explained by exposure misclassification.
PMCID: PMC3340427  PMID: 22472486
7.  The Relationship between Retinal Microvascular Abnormalities and Coronary Heart Disease: A Review 
The American journal of medicine  2010;123(4):374.e1-374.e7.
Heart disease remains the leading cause of death in the United States despite decades of advancement in its diagnosis and treatment. Due to the limitations of traditional risk stratification for heart disease, evaluation of the retinal vasculature has been proposed as an easily and safely measured adjunct to commonly used screening methods. In this article we provide a comprehensive review of the literature concerning the relationships between retinal microvascular abnormalities and coronary heart disease. We outline details of the most recent large epidemiological studies and discuss their potential implications for clinical practice. Finally, we propose a change to the current guidelines regarding the screening of “low risk” women, a group that is often failed by traditional evaluation algorithms.
PMCID: PMC2922900  PMID: 20362758
Coronary heart disease; Retinal microvascular abnormalities; Retinopathy; Risk prediction; Screening
8.  The Effects of EPA+DHA and Aspirin on Inflammatory Cytokines and Angiogenesis Factors 
In a recent study, we showed that the combination of aspirin plus the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) synergistically inhibited platelet function. As aspirin, EPA, and DHA have demonstrated anti-inflammatory properties, we hypothesized that the ingestion of EPA and DHA, with and without aspirin, would reduce plasma levels of inflammatory cytokines and angiogenesis factors more than aspirin alone and before aspirin was ingested.
Using multiplex technology, we investigated the effects of aspirin (single-dose 650 mg on day 1), EPA+DHA (3.4 g/d for days 2-29), and aspirin with EPA+DHA (day 30) on plasma levels of inflammatory cytokines and angiogenesis factors in healthy adults.
Aspirin alone had no effect on any factor versus baseline, but EPA+DHA, with and without aspirin, significantly reduced concentrations of 8 of 9 factors. Although EPA+DHA plus aspirin reduced concentrations of a subset of the factors compared to baseline, neither aspirin alone nor the combination significantly reduced the level of any analyte more robustly than EPA+DHA alone.
These data suggest that EPA+DHA has more pronounced down-regulatory effects on inflammation and angiogenesis than aspirin. The implications of these findings for the use of combined therapy for cardiovascular disease remain to be clarified.
PMCID: PMC3331709  PMID: 22530200
eicosapentaenoic acid; docosahexaenoic acid; lipid mediators; fatty acids; angiogenesis; hemostasis; platelet function; cytokines; aspirin
9.  Determinants of Blood Cell Omega-3 Fatty Acid Content 
Although red blood cell eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) content (the Omega-3 Index) predicts cardiovascular death, the factors determining the Index are unknown.
In 704 outpatients, we undertook an investigation of the clinical determinants of the Index.
Factors associated with the Index in decreasing order were: EPA+DHA supplement use, fish consumption frequency, triglyceride level, age, high cholesterol history, and smoking. These factors explained 59% of Index variability, with capsules/fish intake together accounting for 47%. The Index increased by 13% (p< 0.0001) for each serving level increase in fish intake and EPA+DHA supplementation correlated with a 58% increase (p< 0.0001) regardless of background fish intake (p=0.25; test for interaction). A 100 mg/dL decrease in serum triglycerides was associated with a 15% higher (p<0.0001) Index.
The intake of EPA+DHA-rich foods and supplements principally determined the Omega-3 Index, but explained only about half of the variability.
PMCID: PMC2785093  PMID: 19953197
10.  Impact of Communication on Preventive Services Among Deaf American Sign Language Users 
Deaf American Sign Language (ASL) users face communication and language barriers that limit healthcare communication with their providers. Prior research has not examined preventive services with ASL-skilled clinicians.
The goal of this study was to determine whether provider language concordance is associated with improved receipt of preventive services among deaf respondents.
This cross-sectional study included 89 deaf respondents aged 50–75 years from the Deaf Health Survey (2008), a BRFSS survey adapted for use with deaf ASL users. Association between the respondent's communication method with the provider (i.e., categorized as either concordant–doctor signs or discordant–other) and preventive services use was assessed using logistic regression adjusting for race, gender, income, health status, health insurance, and education. Analyses were conducted in 2010.
Deaf respondents who reported having a concordant provider were more likely to report a greater number of preventive services (OR 3.42; 95% CI:1.31, 8.93; p=0.0122) when compared to deaf respondents who reported having a discordant provider even after adjusting for race, gender, income, health status, health insurance, and education. In unadjusted analyses, deaf respondents who reported having a concordant provider were more likely to receive an influenza vaccination in the past year (OR 4.55; p=0.016) when compared to respondents who had a discordant provider.
Language-concordant patient–provider communication is associated with higher appropriate use of preventive services by deaf ASL users.
PMCID: PMC3117257  PMID: 21665066
11.  High Density Lipoprotein (HDL) Modulation Targets 
Drugs of the future  2010;35(1):33-39.
Given the strong genetic determinants of favorable HDL-C levels, the ability to procure the cardiovascular disease and longevity benefits associated with this mediator of the reverse cholesterol transport pathway through pharmaceutical intervention is challenging. Niacin is still the most robust HDL-C raising pharmaceutical agent on the market at its use leads to elevations up to 35%. Cholesteryl ester transfer protein (CETP) and endothelial lipase (EL) are two targets involved in the reverse cholesterol transport pathway that have become therapeutic targets of various investigations for raising HDL. However, the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial was stopped in December 2006 due to excess mortality in the group of patients treated with torcetrapib, a CETP inhibitor. Other CETP inhibitors being studied include anacetrapib and JTT-705. Other CEPT inhibitors including TA-8995, DRL-17822, JTT-302, and others are under investigation. Additionally a biologic target CETi-1, an investigational vaccine in phase II development designed to elicit antibodies that bind and inhibit the activity of CETP leading to blocking the ability of the protein to transfer cholesterol from HDL to LDL and thus causing HDL cholesterol levels to rise is under clinical investigation for sometime.
PMCID: PMC3381456  PMID: 22740724
High Density lipoprotein (HDL); Low Density lipoprotein (LDL); atherosclerosis; coronary heart disease (CHD); Cholesteryl ester transfer protein (CETP); Endothelial Lipase; Longevity; Stroke; Coronary artery Diseases (CAD); cardiovascular diseases (CVD); Inflammation; genetics; niacin; statins; fibrates
12.  Parenteral Fish Oil-Associated Burr Cell Anemia 
The Journal of Pediatrics  2010;156(2):324-6.e1.
We report the development of burr cell anemia in an infant with short bowel syndrome who received parenteral fish oil (Omegaven, Fresenius-Kabi, Graz, Austria) after development of total parenteral nutrition–associated liver disease. Parenteral fish oil was discontinued, and the burr cell anemia disappeared, suggesting that parenteral fish oil might be associated with hemolytic anemia.
PMCID: PMC3365505  PMID: 20105643
13.  Our Expanding View of Platelet Functions and its Clinical Implications 
Platelets are the primary cell mediator of thrombosis. A deficiency of platelets can result in life threatening bleeding defects. ‘Over active’ platelets contribute to life threatening outcomes in diseases such as heart attack, stroke, and cancer. The use of platelet inhibitors for thrombosis prevention must seek a delicate balance between inhibiting platelet activation and an associated increased bleeding risk. There are currently few platelet inhibitors available for clinical use making the search for novel anti-platelet drugs an ongoing priority. Several newly identified pathways of platelet activation may hold hope in this area. In addition, important roles for platelets beyond hemostasis have gained recent attention. A recognition that platelets contribute to the pathogenesis of inflammatory diseases such as arthritis and hepatitis has expanded our appreciation for the importance of understanding platelet function and platelet derived inflammatory mediators. It has also heightened interest in a continued search for new platelet inhibitors and presents new opportunities for platelet inhibitors to be used in a wide array of disease treatment strategies.
PMCID: PMC3354697  PMID: 20661787
platelet; inflammation; thrombosis; aggregation; activation; therapy
14.  Novel Therapeutic Targets for Preserving a Healthy Endothelium: Strategies for Reducing the Risk of Vascular and Cardiovascular Disease 
Cardiology Journal  2011;18(4):352-363.
The endothelium lies in a strategic anatomical position between the circulating blood and vascular smooth-muscle cells as a source of vasodilators such as nitric oxide, prostacyclin, and hyperpolarizing factor as well as heparin-like substances as well as other molecules with anti-proliferative properties. These effects of endothelial cells may explain why platelets and monocytes usually do not adhere at the blood vessel wall. However, under pathological conditions, endothelial dysfunction occurs and significantly contributes to the increase of platelet-vessel wall interaction, vasoconstriction, pro-inflammation, and proliferation. Under these conditions, endothelium-dependent vasodilation is reduced and endothelium-dependent constrictor responses are augmented. Upon vessel wall injury platelets rapidly adhere to the exposed sub-endothelial matrix which is mediated by several cellular receptors present on platelets or endothelial cells and various adhesive proteins. Subsequent platelet activation results in the recruitment of additional platelets and the generation of platelet aggregates forming a stable platelet plug. Therapeutic strategies aimed at improving or preserving endothelial function therefore may be promising in the prevention and treatment of coronary artery disease. Diagnostic modalities for assessment of endothelial function should allow for the early detection of vascular endothelial dysfunction before the manifestation of serious adverse vascular disorders.
PMCID: PMC3342824  PMID: 21769815
vascular; endothelial cell; cardiovascular disorders; coronary syndrome; vasoconstriction; vasodilation; inflammation; anti-inflammation; anti-platelet; pro-platelet; anticoagulant; pro-coagulant; Diagnosis of endothelial function
15.  Physicians’ Knowledge and Attitudes Regarding Implantable Cardioverter- Defibrillators 
Cardiology Journal  2010;17(3):267-273.
Information is limited regarding the knowledge and attitudes of physicians typically involved in the referral of patients for implantable cardioverter defibrillator (ICD) implantation.
We conducted a survey of primary care physicians and cardiologists at the University of Rochester Medical Center and the Unity Health System Rochester, NY from December 2008 to February 2009. The survey collected information regarding knowledge and attitudes of physicians towards ICD therapy.
Of the 332 surveys distributed, 110 (33%) were returned. Over-all 94 (87%) physicians reported referring patients for ICD implantation. Eighteen (17%) physicians reported unawareness of guidelines for ICD use. Sixty-four (59%) physicians recommended ICD in patients with ischemic cardiomyopathy and left ventricular ejection fraction (LVEF) ≤ 35%. Sixty-five (62%) physicians use ≤ 35% as LVEF criteria for ICD referral in patients with non-ischemic cardiomyopathy. Cardiologists were more familiar than primary care physicians with LVEF criteria for implantation of ICD in patients with ischemic and non-ischemic cardiomyopathy (p value 0.005 and 0.002 respectively). Twenty-nine (27%) participants were unsure regarding benefits of ICDs in eligible women and Blacks. Eighty two (76%) physicians believed that an ICD could benefit patients ≥70 years whereas only 53 (49%) indicated that an ICD would benefit patients ≥ 80 years of age. A lack of familiarity with current clinical guidelines regarding ICD implantation exists. Primary care physicians are less aware of clinical guidelines than are cardiologists. This finding highlights the need to improve the dissemination of guidelines to primary care physicians in an effort to improve ICD utilization.
PMCID: PMC3337764  PMID: 20535717
Implantable cardioverter defibrillator; Physician’s Knowledge; Gender and Racial Disparities
16.  Training Students in Community Health: A Novel Required Fourth-Year Clerkship at the University of Rochester 
Academic Medicine  2008;83(4):357-364.
In 2004, community health became the 4th mission of the University of Rochester Medical Center, along with education, clinical care, and research. In that same year, a novel clerkship was added to the 4th-year curriculum that focuses on the “practice” of community health and preventive medicine. The goal is to offer intensive experiential training to develop skills in community health improvement by partnering with community agencies involved in health promotion and disease prevention. The learning objectives addressed include: community health assessment, risk behavior change, assurance of personal health services, advocacy and policy change, environmental interventions, community organization and partnership-building, and program evaluation. The clerkship involves 3 full days of didactic instruction, followed by 4 weeks of program development and implementation. Each student chooses a project that focuses on a specific target population, then designs it and incorporates public health knowledge, skills, and attitudes learned during the didactic component. Course directors then mentor students during project implementation. Students can begin “longitudinal” experiences in their first or second years to fold into the required clerkship. Innovations include a novel “Advocacy and Policy Change” module and a highly rated “Cultural Determinants of Health” lecture, and a resource-based course website. The clerkship was initially offered as an elective, and has since become a required course. In the clerkship to date, three hundred and forty students have launched hundreds of community-level interventions within various settings locally, nationally, and internationally. Evaluation efforts to date indicate the clerkship has been received favorably by both faculty and students.
PMCID: PMC3332332  PMID: 18367896
17.  Carotid endarterectomy and carotid artery stenting utilization trends over time 
BMC Neurology  2012;12:17.
Carotid endarterectomy (CEA) has been the standard in atherosclerotic stroke prevention for over 2 decades. More recently, carotid artery stenting (CAS) has emerged as a less invasive alternative for revascularization. The purpose of this study was to investigate whether an increase in stenting parallels a decrease in endarterectomy, if there are specific patient factors that influence one intervention over the other, and how these factors may have changed over time.
Using a nationally representative sample of US hospital discharge records, data on CEA and CAS procedures performed from 1998 to 2008 were obtained. In total, 253,651 cases of CEA and CAS were investigated for trends in utilization over time. The specific data elements of age, gender, payer source, and race were analyzed for change over the study period, and their association with type of intervention was examined by multiple logistic regression analysis.
Rates of intervention decreased from 1998 to 2008 (P < 0.0001). Throughout the study period, endarterectomy was the much more widely employed procedure. Its use displayed a significant downward trend (P < 0.0001), with the lowest rates of intervention occurring in 2007. In contrast, carotid artery stenting displayed a significant increase in use over the study period (P < 0.0001), with the highest intervention rates occurring in 2006. Among the specific patient factors analyzed that may have altered utilization of CEA and CAS over time, the proportion of white patients who received intervention decreased significantly (P < 0.0001). In multivariate modeling, increased age, male gender, white race, and earlier in the study period were significant positive predictors of CEA use.
Rates of carotid revascularization have decreased over time, although this has been the result of a reduction in CEA despite an overall increase in CAS. Among the specific patient factors analyzed, age, gender, race, and time were significantly associated with the utilization of these two interventions.
PMCID: PMC3355040  PMID: 22458607
18.  An Epidemiologic Transition of Cardiovascular Disease Risk in Carriacou and Petite Martinique, Grenada: the Grenada Heart Project, 2005-2007 
The epidemiologic transition has made chronic disease a major health threat in the Caribbean and throughout the world. Our objective was to examine the pattern of lifestyle factors associated with cardiovascular disease (CVD) in Grenada and to determine whether the prevalence of CVD  risk factors differs by subgroups.
We conducted a cross-sectional study of adult Grenadians between 2005 and 2007. We used a population-wide, community-based approach by adapting the World Health Organization's STEPwise Approach to the Surveillance of Chronic Disease survey for a local context. We collected behavioral, anthropometric, and blood sample data to assess the prevalence of CVD risk factors.
An estimated 64% (n = 2,017) of 3,167 eligible adults participated in our study (60% women). With increasing age, consumption of fried foods declined, whereas fish intake increased. Adults aged 45 to 54 years had the highest obesity rate (39%). Large waist circumference was more common among women than among men. According to National Cholesterol Education Program criteria, 29% of participants had metabolic syndrome (47% ≥65 y; 36% women vs 17% men). Approximately one-fifth of participants had lived outside Grenada for more than 10 years. Participants who had migrated tended to be older and have different CVD risk factors than those who had never migrated.
In the midst of an epidemiologic transition in the Caribbean nation of Grenada in which CVD risk is increasing, dietary risk factors are most prevalent among women and among all adults younger than 55.
PMCID: PMC3406739  PMID: 22515972
19.  Altered Cholesterol and Fatty Acid Metabolism in Huntington Disease 
Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease.
PMCID: PMC2926984  PMID: 20802793
Huntington disease; cholesterol; triglycerides; insulin resistance; omega-3 fatty acids
20.  Omega-6 and trans fatty acids in blood cell membranes: a risk factor for acute coronary syndromes? 
American heart journal  2008;156(6):1117-1123.
Although fatty acid intake has been associated with risk of coronary disease events, the association between blood omega-6 and trans-fatty acids (FAs) at the time of an acute coronary syndrome (ACS) is unknown.
The relationship of blood FA composition to ACS was analyzed in 768 incident cases and 768 controls (matched on age, sex, and race).
Compared to controls, ACS cases’ blood cell membrane content of linoleic acid was 13% lower (p<0.0001); arachidonic acid was 3.6% higher (p<0.001); the trans isomer of oleic acid was 13.3% higher (p<0.0001); and the trans-trans isomer of linoleic acid was 13.3% higher (p=0.003). In multivariable analyses, a 1-standard deviation (SD) decrease in linoleic acid was associated with >3 times the odds for being a case {OR=3.23 {95% CI, 2.63–4.17)}. The relationship of arachidonic acid to ACS was U-shaped; compared to the first quartile of arachidonic acid, the ORs for case status in the second, third and fourth quartiles were 0.73 (95% CI: 0.47–1.13), 0.65 (95% CI: 0.41–1.04), and 2.32 (95% CI: 1.39–3.90). The OR for a 1-SD increase in trans oleic acid was 1.24 (95% CI; 1.06 to 1.45) and for trans-trans linoleic acid, 1.1 (95% CI; 0.93–1.30). All associations were independent of membrane omega-3 FA content.
High blood levels of linoleic acid but low levels of trans oleic acid are inversely associated with ACS. The relationship of arachidonic acid to ACS appears more complex.
PMCID: PMC2596644  PMID: 19033007

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