Cardiorespiratory Fitness Associates with Cerebral Vessel Pulsatility in a Cohort Enriched with Risk for Alzheimer's Disease.

BACKGROUND: There is increasing evidence that vascular disease risk factors contribute to evolution of the dementia syndrome of Alzheimer's disease (AD). One important measure of cerebrovascular health is pulsatility index (PI) which is thought to represent distal vascular resistance, and has previously been reported to be elevated in AD clinical syndrome. Physical inactivity has emerged as an independent risk factor for cardiovascular disease. OBJECTIVE: This study aims to examine the relationship between a measure of habitual physical activity, cardiorespiratory fitness (CRF), and PI in the large cerebral vessels. METHODS: Ninety-two cognitively-healthy adults (age = 65.34±5.95, 72% female) enrolled in the Wisconsin Registry for Alzheimer's Prevention participated in this study. Participants underwent 4D flow brain MRI to measure PI in the internal carotid artery (ICA), basilar artery, middle cerebral artery (MCA), and superior sagittal sinus. Participants also completed a self-report physical activity questionnaire. CRF was calculated using a previously-validated equation that incorporates sex, age, body-mass index, resting heart rate, and self-reported physical activity. A series of linear regression models adjusted for age, sex, APOE4 status, and 10-year atherosclerotic cardiovascular disease risk were used to analyze the relationship between CRF and PI. RESULTS: Inverse associations were found between CRF and mean PI in the inferior ICA (p = .001), superior ICA (p = .035), and basilar artery (p = .040). No other cerebral vessels revealed significant associations between CRF and PI (p≥.228). CONCLUSIONS: Higher CRF was associated with lower PI in several large cerebral vessels. Since increased pulsatility has been associated with poor brain health and reported in persons with AD, this suggests that aerobic fitness might provide protection against cerebrovascular changes related to the progression of AD clinical syndrome.

Brachial Artery Echogenicity and Grayscale Texture Changes in HIV-Infected Individuals Receiving Low-Dose Methotrexate.

Objective- We evaluated the biological effects of low-dose methotrexate on 3 novel brachial artery grayscale ultrasound measures that may indicate subclinical arterial injury. Approach and Results- Exploratory analysis from a clinical trial of people with HIV infection at increased cardiovascular disease risk who were randomly assigned to low-dose methotrexate (target dose 15 mg/wk) or placebo. Brachial artery ultrasound grayscale median, gray level difference statistic texture-contrast (GLDS-CON), and gray level texture entropy were measured at baseline and after 24 weeks of intervention. Findings from the intention-to-treat (N=148) and adequately-dosed (N=118) populations were consistent, so the adequately-dosed population results are presented. Participants were a median (Q1, Q3) age of 54 (50, 60) years. After 24 weeks, the low-dose methotrexate intervention was associated with a 25.4% (-18.1, 58.6; P=0.007) increase in GLDS-CON compared with 1.3% (-29.1, 44.7; P=0.97) with placebo ( P=0.05) and a 0.10 u (-0.06, 0.23; P=0.026) increase in entropy compared with 0.02 u (-0.11, 0.14; P=0.54) with placebo ( P=0.14). At week 24, changes in CD4+ T cells correlated inversely with changes in GLDS-CON (ρ=-0.20; P=0.031), and entropy (ρ=-0.21; P=0.023). Changes in D-dimer levels, but no other inflammatory biomarkers, also correlated inversely with changes in GLDS-CON (ρ=-0.23; P=0.014) and entropy (ρ=-0.26; P=0.005). Conclusions- Brachial artery GLDS-CON and entropy increased after 24 weeks of low-dose methotrexate, though the latter was not significantly different from placebo. Grayscale changes were associated with decreases in CD4+ T-cell and D-dimer concentrations and may indicate favorable arterial structure changes.

Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: The ACTG (AIDS Clinical Trials Group) Study 5152s.

OBJECTIVES: This study evaluated the effects of 3 class-sparing antiretroviral therapy (ART) regimens on endothelial function in human immunodeficiency virus (HIV)-infected subjects participating in a randomized trial. BACKGROUND: Endothelial dysfunction has been observed in patients receiving ART for HIV infection. METHODS: This was a prospective, multicenter study of treatment-naive subjects who were randomly assigned to receive a protease inhibitor-sparing regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + efavirenz, a non-nucleoside reverse transcriptase inhibitor-sparing regimen of NRTIs + lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. The NRTIs were lamivudine + stavudine, zidovudine, or tenofovir. Brachial artery flow-mediated dilation (FMD) was determined by B-mode ultrasound before starting on ART, then after 4 and 24 weeks. RESULTS: There were 82 subjects (median age 35 years, 91% men, 54% white). Baseline CD4 cell counts and plasma HIV ribonucleic acid (RNA) values were 245 cells/mm(3) and 4.8 log(10) copies/ml, respectively. At baseline, FMD was 3.68% (interquartile range [IQR] 1.98% to 5.51%). After 4 and 24 weeks of ART, plasma HIV RNA decreased by 2.1 and 3.0 log(10) copies/ml, respectively. FMD increased by 0.74% (IQR -0.62% to +2.74%, p = 0.003) and 1.48% (IQR -0.20% to +4.30%, p < 0.001), respectively, with similar changes in each arm (Kruskal-Wallis p value >0.600). The decrease in plasma HIV RNA at 24 weeks was associated with greater FMD (r(s) = -0.30, p = 0.017). CONCLUSIONS: Among treatment-naive individuals with HIV, 3 different ART regimens rapidly improved endothelial function. Benefits were similar for all ART regimens, appeared quickly, and persisted at 24 weeks.

Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy.

BACKGROUND: Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. OBJECTIVE: To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. METHODS: This was a substudy of a prospective, multicenter study treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. RESULTS: Among the 82 participants, total and small low-density lipoprotein concentrations increased (median, interquartile range) by 152 (-49 - +407, p<0.01) and 130 (-98 - +417, p<0.01) nmol/L, respectively, especially in the arms containing lopinavir/ritonavir (p(KW)<0.04). Very low-density lipoproteins also increased (p<0.01), with a larger increase in the arms that contained lopinavir/ritonavir (p=0.022). High-density lipoproteins increased by 6.0 nmol/L (2.8 - 10.4, p<0.01), but differences between arms were not significant (p(KW)=0.069). Changes were not related to changes in markers of insulin/glucose metabolism. CONCLUSIONS: Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir.