المؤلفون: Devineni, Divya, Akbarpour, Meleeka, Gong, Yufan, Wong, Nathan

المصدر: Cardiovascular Drugs and Therapy. 38(2)

مصطلحات موضوعية: Cardiovascular risk, Diabetes, GLP-1 receptor agonists, SGLT2-inhibitors, Adult, Male, Humans, Glycemic Control, Precision Medicine, Cardiovascular Diseases, Sodium-Glucose Transporter 2, Risk Factors, Population Health, Diabetes Mellitus, Heart Disease Risk Factors, Atherosclerosis, Glucagon-Like Peptide 1, Glucose, Diabetes Mellitus, Type 2, Glucagon-Like Peptide-1 Receptor, Hypoglycemic Agents

الوصف: PURPOSE: Data are limited on sodium glucose co-transport 2 inhibitors (SGLT2-is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among real-world cohorts of underrepresented patients. We examined these therapies and glycemic control in US adults with diabetes mellitus (DM) by atherosclerotic cardiovascular disease (ASCVD) risk and sociodemographic factors. METHODS: In the NIH Precision Medicine Initiative All of Us Research Program, we categorized DM as (1) moderate risk, (2) high risk, and (3) with ASCVD. We examined proportions on DM therapies, including SGLT2-i or GLP-1 RA, and at glycemic control by sociodemographic factors and CVD risk groups. RESULTS: Our 81,332 adults aged ≥ 18 years with DM across 340 US sites included 22.3% non-Hispanic Black, 17.2% Hispanic, and 1.8% Asian participants; 31.1%, 30.3%, and 38.6% were at moderate risk, high risk, or with ASCVD, respectively. Those with DM and ASCVD were most likely on SGLT2-i (8.6%) or GLP-1 RA (11.9%). SGLT2-i use was

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4qr8161gTest

المؤلفون: Lake, Jordan E, Wang, Ruibin, Barrett, Benjamin W, Bowman, Emily, Hyatt, Ana N, Debroy, Paula, Candelario, Jury, Teplin, Linda, Bodnar, Kaitlin, McKay, Heather, Plankey, Michael, Brown, Todd T, Funderburg, Nicholas, Currier, Judith S

المصدر: AIDS. 36(13)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Prevention, Cardiovascular, HIV/AIDS, Infectious Diseases, Good Health and Well Being, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Adult, Biomarkers, Cardiovascular Diseases, Cohort Studies, Endothelins, Female, HIV Infections, Hormones, Humans, Inflammation, Interleukin-6, Interleukin-8, Lipopolysaccharide Receptors, Lipoproteins, LDL, Male, Middle Aged, P-Selectin, Plasminogen Activator Inhibitor 1, Receptor for Advanced Glycation End Products, von Willebrand Factor, cardiovascular biomarkers, feminizing hormonal therapy, HIV, trans women, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences

الوصف: BackgroundFeminizing hormonal therapy (FHT) and HIV potentially alter cardiovascular disease (CVD) risk in transgender women (TW).MethodsTW were enrolled in Los Angeles, California and Houston, Texas and frequency-matched to Multicenter AIDS Cohort Study cisgender men (CM) on age, race, substance use, and abacavir use. Biomarkers of CVD risk and inflammation were assessed via ELISA. Wilcoxon rank sum and Fisher's exact tests compared TW and CM. Multivariable linear regression assessed factors associated with biomarker concentrations.ResultsTW (HIV+ n  = 75, HIV- n  = 47) and CM (HIV+ n  = 40, HIV- n  = 40) had mean age 43-45 years; TW/CM were 90%/91% non-Hispanic Black, Hispanic, or Multiracial, 26%/53% obese, and 34%/24% current smokers; 67% of TW were on FHT. Among people with HIV (PWH), TW had higher median extracellular newly-identified receptor for advanced glycation end-products (EN-RAGE), lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), soluble tumor necrosis factor receptor type (sTNFR) I/II, interleukin (IL)-8 and plasminogen activator inhibitor (PAI)-1, but lower soluble CD14, von Willebrand factor (vWF) and endothelin (ET)-1 levels than CM. Findings were similar for participants without HIV (all P

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الوصول الحر: https://escholarship.org/uc/item/7842k8nbTest

المؤلفون: Jenkins, Alicia, Braffett, Barbara, Basu, Arpita, Bebu, Ionut, Dagogo-Jack, Samuel, Orchard, Trevor, Wallia, Amisha, Lopes-Virella, Maria, Garvey, W, Lachin, John, Lyons, Timothy

المصدر: Scientific Reports. 11(1)

مصطلحات موضوعية: Adult, Cardiovascular Diseases, Diabetes Mellitus, Type 1, Female, Heart Disease Risk Factors, Humans, Male, Metabolic Syndrome, Middle Aged, Uric Acid

الوصف: In type 2 diabetes, hyperuricemia is associated with cardiovascular disease (CVD) and the metabolic syndrome (MetS), but associations in type 1 diabetes (T1D) have not been well-defined. This study examined the relationships between serum urate (SU) concentrations, clinical and biochemical factors, and subsequent cardiovascular events in a well-characterized cohort of adults with T1D. In 973 participants with T1D in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), associations were defined between SU, measured once in blood collected 1997-2000, and (a) concurrent MetS and (b) incident any CVD and major adverse cardiovascular events (MACE) through 2013. SU was higher in men than women [mean (SD): 4.47 (0.99) vs. 3.39 (0.97) mg/dl, respectively, p

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7806b8k2Test
https://escholarship.org/content/qt7806b8k2/qt7806b8k2.pdfTest

المؤلفون: Basu, Arpita, Bebu, Ionut, Jenkins, Alicia J, Stoner, Julie A, Zhang, Ying, Klein, Richard L, Lopes-Virella, Maria F, Garvey, W Timothy, Budoff, Matthew J, Alaupovic, Petar, Lyons, Timothy J, Group, the Diabetes Control Complications Trial Epidemiology of Diabetes Interventions Complications Research

المصدر: Journal of Lipid Research. 60(8)

مصطلحات موضوعية: Medical Biochemistry and Metabolomics, Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Cardiovascular, Atherosclerosis, Prevention, Heart Disease, Heart Disease - Coronary Heart Disease, Good Health and Well Being, Adult, Apolipoproteins, Cardiovascular Diseases, Diabetes Complications, Diabetes Mellitus, Type 1, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, apolipoprotein C3, major adverse cardiac event, type 1 diabetes, Diabetes Control Complications Trial/Epidemiology of Diabetes Interventions Complications Research Group, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical biochemistry and metabolomics

الوصف: APOB, APOC3, and APOE and apolipoprotein-defined lipoprotein subclasses (ADLSs; based on qualitative apolipoprotein complement) have been associated with dyslipidemia and CVD. Our main objective was to define associations of serum apolipoproteins and ADLSs with "any CVD" and "major atherosclerotic cardiovascular events" (MACEs) in a prospective study of T1D. Serum apolipoproteins and ADLSs (14 biomarkers in total) were measured in sera (obtained between 1997 and 2000) from a subset (n = 465) of the Epidemiology of Diabetes Interventions and Complications cohort. Prospective associations of "any CVD" (myocardial infarction, stroke, confirmed angina, silent myocardial infarction, revascularization, or congestive heart failure) and MACEs (fatal or nonfatal myocardial infarction or stroke), over 5,943 and 6,180 patient-years follow-up, respectively, were investigated using Cox proportional hazards models that were unadjusted and adjusted for risk factors. During 15 years of follow-up, 50 "any CVD" events and 24 MACEs occurred. Nominally significant positive univariate associations with "any CVD" were APOB, APOC3 and its subfractions [heparin precipitate, heparin-soluble (HS)], and ADLS-defined Lp-B. In adjusted analyses, APOC3-HS remained nominally significant. Nominally significant positive univariate associations with MACEs were APOC3 and its subfractions and Lp-B:C; those with total APOC3 and APOC3-HS persisted in adjusted analyses. However, these associations did not reach significance after adjusting for multiple testing. There were no significant associations of APOA1, APOA2, APOE, or other ADLSs with either "any CVD" or MACEs. These hypothesis-generating data suggest that total serum APOC3 and APOC3 in HDL are potentially important predictive biomarkers for any CVD and MACEs in adults with T1D.

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الوصول الحر: https://escholarship.org/uc/item/8046r195Test

المؤلفون: Ehrmann, Dominic, Chatwin, Hannah, Schmitt, Andreas, Soeholm, Uffe, Kulzer, Bernhard, Axelsen, Johanne Lundager, Broadley, Melanie, Haak, Thomas, Pouwer, Frans, Hermanns, Norbert

المصدر: Ehrmann , D , Chatwin , H , Schmitt , A , Soeholm , U , Kulzer , B , Axelsen , J L , Broadley , M , Haak , T , Pouwer , F & Hermanns , N 2023 , ' Reduced heart rate variability in people with type 1 diabetes and elevated diabetes distress : Results from the longitudinal observational DIA-LINK1 study ' , Diabetic medicine : a journal of the British Diabetic Association , vol. 40 , no. 4 , e15040 . https://doi.org/10.1111/dme.15040Test

مصطلحات موضوعية: cardiovascular health, depression, diabetes distress, heart rate variability, type 1 diabetes, Cardiovascular Diseases, Heart Rate/physiology, Prospective Studies, Humans, Middle Aged, Blood Glucose/analysis, Blood Glucose Self-Monitoring, Adult, Diabetes Mellitus, Type 1

الوصف: Aims: People with type 1 diabetes have a higher risk for cardiovascular disease (CVD). Reduced heart rate variability (HRV) is a clinical marker for CVD. In this observational study using continuous HRV measurement across 26 days, we investigated whether psychological stressors (diabetes distress, depressive symptoms) and glycaemic parameters (hypo- and hyperglycaemic exposure, glycaemic variability and HbA 1c ) are associated with lower HRV in people with type 1 diabetes. Methods: Data from the non-interventional prospective DIA-LINK1 study were analysed. At baseline, depressive symptoms and diabetes distress were assessed. Glucose values and HRV were recorded daily for 26 days using continuous glucose monitoring (CGM) and a wrist-worn health tracker respectively. Multilevel modelling with participant as nesting factor was used to analyse associations between day-to-day HRV and diabetes distress, depressive symptoms and CGM-derived parameters. Results: Data from 149 participants were analysed (age: 38.3 ± 13.1 years, HbA 1c : 8.6 ± 1.9%). Participants with elevated diabetes distress had a significantly lower HRV across the 26 days compared to participants without elevated distress (β = −0.28; p = 0.004). Elevated depressive symptoms were not significantly associated with HRV (β = −0.18; p = 0.074). Higher daily exposure to hyperglycaemia (β = −0.44; p = 0.044), higher average exposure to hypoglycaemia (β = −0.18; p = 0.042) and higher HbA 1c (β = −0.20; p = 0.018) were associated with reduced HRV across the 26 days. Sensitivity analysis with HRV averaged across all days corroborated these results. Conclusions: Diabetes distress is a clinically meaningful psychosocial stressor that could play a role in the cardiovascular health of people with type 1 diabetes. These findings highlight the need for integrated psychosocial care in diabetes management.

الإتاحة: https://doi.org/10.1111/dme.15040Test
https://pure.au.dk/portal/da/publications/reduced-heart-rate-variability-in-people-with-typeTest-1-diabetes-and-elevated-diabetes-distress(8def2f0c-e702-429a-a6b5-971650097692).html

المؤلفون: Samadi, Sara, Abolbashari, Samaneh, Meshkat, Zahra, Mohammadpour, Amir Hooshang, Kelesidis, Theodoros, Gholoobi, Aida, Mehramiz, Mehrane, Tabadkani, Mahla, Sadabadi, Fatemeh, Dalirfardouei, Razieh, Ferns, Gordon A, Ghayour‐Mobarhan, Majid, Avan, Amir

المصدر: BioFactors. 45(3)

مصطلحات موضوعية: Biochemistry and Cell Biology, Biological Sciences, Heart Disease, Atherosclerosis, Prevention, Clinical Research, Cardiovascular, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Adult, Biomarkers, Cardiovascular Diseases, Cholesterol, HDL, Female, Human T-lymphotropic virus 1, Humans, Lipoproteins, HDL, Male, Middle Aged, Risk Factors, Software, Triglycerides, high-density lipoprotein, HDL lipid peroxidation, HDLox, HTLV1 infection, viral infectious disease, Biochemistry & Molecular Biology, Biochemistry and cell biology

الوصف: High-density lipoprotein (HDL) is thought to be protective against cardiovascular disease (CVD), and HDL dysfunction is considered to be a risk factor for CVD. It is unclear whether there is an association between Human T lymphotropic virus type 1 (HTLV1) infection and CVD risk. We have assessed HDL lipid peroxidation (HDLox) as a marker of HDL dysfunction and CVD risk in a subgroup of the MASHAD cohort study. One hundred and sixty two individuals including 50 subjects positive for HTLV1 infection and 112 individuals negative for HTLV1 infection were recruited. Anthropometric and biochemical parameters including serum hs-CRP, fasted lipid profile (HDL-C, LDL, triglycerides, and cholesterol), and fasting blood glucose were determined. Serum HDLox was also measured in the study participants. Multivariate analyses were used to evaluate the association between serum HDLox and HTLV1 infection. None of the traditional CVD risk factors were associated with HTLV1 infection, including serum HDL-C. However, serum HDLox was independently associated with the presence of HTLV1 infection. Logistic regression analysis showed that subjects who were positive for HTLV1 infection were also significantly more likely than uninfected individuals to have higher HDLox (odds ratio 9.35, 95%CI: 3.5-24.7; P < 0.001). HDLox was increased approximately 20% (P < 0.001) in infected subjects compared to the uninfected group. Serum HDLox is a marker of CVD risk factor and increased in individuals affected by HTLV1 infection compared to healthy subjects. © 2019 BioFactors, 45(3):374-380, 2019.

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الوصول الحر: https://escholarship.org/uc/item/8ct7p6t4Test

المؤلفون: Butterfield, Tiffany R, Hanna, David B, Kaplan, Robert C, Kizer, Jorge R, Durkin, Helen G, Young, Mary A, Nowicki, Marek J, Tien, Phyllis C, Golub, Elizabeth T, Floris-Moore, Michelle A, Titanji, Kehmia, Fischl, Margaret A, Heath, Sonya L, Martinson, Jefferey, Crowe, Suzanne M, Palmer, Clovis S, Landay, Alan L, Anzinger, Joshua J

المصدر: AIDS. 31(2)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Immunology, Cardiovascular, HIV/AIDS, Heart Disease, Good Health and Well Being, ADP-ribosyl Cyclase 1, Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Cardiovascular Diseases, Carotid Arteries, Carotid Intima-Media Thickness, Female, Flow Cytometry, Glucose Transporter Type 1, HIV Infections, Humans, Longitudinal Studies, Membrane Glycoproteins, Middle Aged, Monocytes, T-Lymphocytes, cardiovascular disease, GLUT1, HIV, monocyte, T cell, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences

الوصف: ObjectivePeople living with HIV (PLWH) have chronic immune activation and increased cardiovascular disease (CVD) risk. Activation of monocytes and T lymphocytes causes upregulation of glucose transporter-1 (GLUT1) for efficient function. PLWH have an increased percentage of GLUT1-expressing monocytes and T lymphocytes, but it is unclear if these cells are associated with CVD. We evaluated the expression of GLUT1 and CD38 on monocyte and T lymphocyte populations from HIV-infected women with subclinical CVD.MethodsParticipants with more than 75th percentile (n = 15) and less than 25th percentile (n = 15) age-adjusted intima-media thickness (IMT) at the right common carotid artery and bifurcation were identified from the Women's Interagency HIV Study. Groups were matched by age, race/ethnicity, smoking status, and CD4 cell count. All women were receiving suppressive antiretroviral therapy except for one high and one low IMT participant. Monocyte and T lymphocyte populations were evaluated for GLUT1 and CD38 expression using flow cytometry.ResultsIntermediate monocytes from high IMT women had significantly increased expression of GLUT1 (310 MFI vs. 210 MFI, P = 0.024) (66.4% vs. 48.5%, P = 0.031) and CD38 (339 MFI vs. 211 MFI, P = 0.002) (10.5% vs. 3.8%, P = 0.0002) compared with women with low IMT. High and low IMT participants showed no differences in GLUT1 or CD38 expression on classical monocytes, nonclassical monocytes, CD4 and CD8 T lymphocytes.ConclusionGLUT1-expressing intermediate monocytes are elevated in HIV-infected women with subclinical CVD. These cells may contribute to development of CVD in PLWH and could be a novel target to limit inflammation.

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الوصول الحر: https://escholarship.org/uc/item/7md446ttTest

المؤلفون: Delshad Aghdam, Saeideh, Siassi, Fereydoun, Nasli Esfahani, Ensieh, Qorbani, Mostafa, Rajab, Asadollah, Sajjadpour, Zahra, Bashiri, Anahita, Aghayan, Maryam, Sotoudeh, Gity

المصدر: BMC Cardiovascular Disorders; 6/12/2021, Vol. 21 Issue 1, p1-11, 11p

مصطلحات موضوعية: TYPE 1 diabetes, LDL cholesterol, CARDIOVASCULAR diseases risk factors, HDL cholesterol, CARDIOVASCULAR diseases, BLOOD lipids, TYPE 2 diabetes

مستخلص: Background: Dietary phytochemical index (DPI) is useful and inexpensive method to identify the role of phytochemicals on cardiovascular disease (CVD) risk factors. This study aimed to assess the relationship between DPI and CVD risk factors in patients with type1 diabetes mellitus.Methods: A total of 261 participants aged 18-35 years with T1DM were enrolled in this cross-sectional study to assess the relationship between DPI and CVD risk factors. Anthropometric measurements, blood lipids, glucose, and antioxidant level were measured. Food intakes were determined using a food frequency questionnaire to calculate DPI. Logistic regression was used.Results: The mean age of participants was 25 years. After adjustment for potential confounders, participants in the highest tertile of DPI had 88 % lower chance of hyperglycemia (P for trend = 0.020), 81 % lower chance of low high-density lipoprotein cholesterol (HDL-C) (P for trend = 0.030) and 98 % lower chance of high low-density lipoprotein cholesterol to HDL-C ratio (P for tend = 0.040). There were no relationships between DPI and other CVD risk factors.Conclusions: Although higher intake of phytochemical-rich foods had a beneficial effect on some risk factors of CVD, more studies more studies are warranted to corroborate the present findings. [ABSTRACT FROM AUTHOR]

: Copyright of BMC Cardiovascular Disorders is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Watkins, Deborah J, Wellenius, Gregory A, Butler, Rondi A, Bartell, Scott M, Fletcher, Tony, Kelsey, Karl T

مصطلحات موضوعية: Genetics, Adult, Alkanesulfonic Acids, Biomarkers, Caprylates, Cardiovascular Diseases, DNA Methylation, Epigenesis, Genetic, Female, Fluorocarbons, Humans, Long Interspersed Nucleotide Elements, Male, Middle Aged, Risk Factors, Perfluorooctanoic acid, Perfluorooctane sulfonate, Epigenetics, DNA methylation, LINE-1, Cardiovascular disease, carbon chain, referring to perfluorooctanoic acid, BMI, C8, CDC, CVD, Centers for Disease Control and Prevention, HDL-C, IQR, IRB, Institutional Review Board, LDL-C, NHANES, NIOSH, National Health and Nutrition Examination Survey, National Institute for Occupational Safety and Health, PFAA, PFHxS, PFNA, PFOA, PFOS, PPAR, body mass index, cardiovascular disease, high density lipoprotein cholesterol, interquartile range, long interspersed nuclear element 1, low density lipoprotein cholesterol, perfluoroalkyl acid, perfluorohexane sulfonate, perfluorononanoic acid, perfluorooctane sulfonate, perfluorooctanoic acid, peroxisome-proliferator activated receptor, Environmental Sciences

الوصف: Perfluoroalkyl acids (PFAAs) are persistent, synthetic compounds that are used in a number of consumer products. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been associated with cardiovascular risk factors, and changes in gene expression and DNA methylation in animals and cellular systems. However, whether PFAA exposure is associated with LINE-1 DNA methylation, a potential marker of cardiovascular risk, in humans remains unknown. We sought to evaluate the cross-sectional associations between serum PFAAs and LINE-1 DNA methylation in a population highly exposed to PFOA. We measured serum PFAAs twice four to five years apart in 685 adult participants (47% male, mean age±SD=42±11years). We measured percent LINE-1 DNA methylation in peripheral blood leukocytes at the second time point (follow-up), and estimated absolute differences in LINE-1 methylation associated with an interquartile (IQR) shift in mean PFAA serum levels. IQR increases in mean serum PFOA, PFOS, perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were associated with differences of -0.04 (p=0.16), 0.20 (p=0.001), 0.06 (p=0.19), and 0.02 (p=0.57), respectively, in % LINE-1 methylation at follow-up after adjustment for potential confounders. We observed a monotonic increase in LINE-1 DNA methylation across tertiles of PFOS and PFNA (ptrend=0.02 for both associations), but not across tertiles of PFOA or PFHxS (ptrend=0.71 and 0.44, respectively). In summary, serum PFOS was associated with LINE-1 methylation, while serum PFOA, PFHxS, and PFNA were not. Additional research is needed to more precisely determine whether these compounds are epigenetically active.

الوصول الحر: https://escholarship.org/uc/item/1vp7s3dqTest

المؤلفون: Choquet, Hélène, Nelson, Jeffrey, Pawlikowska, Ludmila, McCulloch, Charles E, Akers, Amy, Baca, Beth, Khan, Yasir, Hart, Blaine, Morrison, Leslie, Kim, Helen

المصدر: Cerebrovascular diseases (Basel, Switzerland). 37(1)

مصطلحات موضوعية: Brain, Humans, Hemangioma, Cavernous, Central Nervous System, Cerebral Hemorrhage, Cardiovascular Diseases, Genetic Predisposition to Disease, Microtubule-Associated Proteins, Proto-Oncogene Proteins, Magnetic Resonance Imaging, Body Mass Index, Risk Factors, Cohort Studies, Cross-Sectional Studies, Age of Onset, Quantitative Trait, Heritable, Mutation, Missense, Point Mutation, Adolescent, Adult, Middle Aged, Child, Hispanic Americans, Mexico, Female, Male, Young Adult, KRIT1 Protein, Hispanic or Latino, Obesity, Clinical Research, Neurosciences, Prevention, Rare Diseases, Tobacco, Tobacco Smoke and Health, Brain Disorders, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Cerebrovascular disease, Familial cerebral cavernous malformations type 1, Common Hispanic mutation, Disease severity, Brain lesion count, Intracerebral hemorrhage, Cardiovascular risk factors, Clinical Sciences, Neurology & Neurosurgery

الوصف: BackgroundCerebral cavernous malformations (CCM) are enlarged vascular lesions affecting 0.1-0.5% of the population worldwide and causing hemorrhagic strokes, seizures, and neurological deficits. Familial CCM type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and is characterized by multiple brain lesions whose number and size increase with age. The number of lesions varies widely for unknown reasons, even among carriers of similar ages with the same mutation. The purpose of this study was to investigate whether cardiovascular (CV) risk factors influence potential markers of familial CCM1 disease severity, such as lesion count and history of intracerebral hemorrhage.MethodsWe analyzed baseline data from 185 Hispanic subjects, enrolled in the Brain Vascular Malformation Consortium study between June 2010 and March 2013. All subjects were carriers of the founder Q455X 'Common Hispanic Mutation' (CHM) in the KRIT1 gene, and had a clinical diagnosis of CCM or had an affected first- or second-degree relative with CCM. We performed a cross-sectional study, collecting detailed clinical information of CCM1-CHM subjects and cerebral susceptibility-weighted magnetic resonance imaging to assess lesion count. Linear or logistic regression analysis of log-lesion count or history of intracerebral hemorrhage and CV risk factors (age, gender, obesity, diabetes, hypertension, hyperlipidemia and smoking status) and related quantitative traits (body mass index, glycosylated hemoglobin levels, blood pressure, lipids levels and pack-years of cigarette smoking) was performed accommodating familial clustering.ResultsCCM1-CHM subjects were mainly female (63.8%) and symptomatic at presentation (63.2%). Lesion count was highly variable (mean ± SD: 57.7 ± 110.6; range: 0-713); 90% of CCM1-CHM subjects had multiple lesions at enrollment. Age (p < 0.001) was positively correlated with lesion count and male gender (p = 0.035) was associated with a greater number of lesions. Obesity (p = 0.001) and higher body mass index (p = 0.002) were associated with fewer lesions. No association with hypertension was detected, however, systolic blood pressure (p = 0.002) was associated with fewer lesions. No significant association with lesion count was observed for diabetes, hyperlipidemia, smoking status or for related quantitative traits. History of intracerebral hemorrhage was not significantly associated with any CV risk factors, however, we found borderline associations of hemorrhage with obesity (p = 0.062), systolic blood pressure (p = 0.083) and pack-years of cigarette smoking (p = 0.055). After correction for multiple testing, age and obesity remained significantly associated with lesion count in CCM1-CHM subjects.ConclusionsThese results suggest that several CV risk factors explain some of the variability in lesion count in Hispanic CCM1-CHM subjects. Although age, gender, obesity, body mass index and systolic blood pressure may influence familial CCM1 disease severity, further longitudinal studies in larger sample sizes are essential to confirm these findings.

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الوصول الحر: https://escholarship.org/uc/item/3p82443tTest