Dear Julie,
Cardiovascular disease remains the number one cause of death in the United States. It is a largely preventable disease, and lifestyle modifications are paramount in preventing it. In last week’s wellness spotlight, the caliber of retinal vasculature was highlighted as a predictor of cardiovascular disease. In this week’s spotlight, we carry over the theme of cardiovascular disease as we once again highlight omega 3’s. We will also look at an article published in JAMA Neurology on vascular risk scores in early adulthood as a greater predictor of brain volume changes and dementia in later life than vascular risk factors in later adulthood.
Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants
Yang Hu, ScD; Frank B. Hu, MD, PhD; JoAnn E. Manson, MD, DrPH
Background-—Whether marine omega-3 supplementation is associated with reduction in risk of cardiovascular disease (CVD) remains controversial.
Methods and Results-—This meta-analysis included study-level data from 13 trials. The outcomes of interest included myocardial infarction, coronary heart disease (CHD) death, total CHD, total stroke, CVD death, total CVD, and major vascular events. The unadjusted rate ratios were calculated using a fixed-effect meta-analysis. A meta-regression was conducted to estimate the dose– response relationship between marine omega-3 dosage and risk of each prespecified outcome. During a mean treatment duration of 5.0 years, 3838 myocardial infarctions, 3008 CHD deaths, 8435 total CHD events, 2683 strokes, 5017 CVD deaths, 15 759 total CVD events, and 16 478 major vascular events were documented. In the analysis excluding REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), marine omega-3 supplementation was associated with significantly lower risk of myocardial infarction (rate ratio [RR] [95% CI]: 0.92 [0.86, 0.99]; P=0.020), CHD death (RR [95% CI]: 0.92 [0.86, 0.98]; P=0.014), total CHD (RR [95% CI]: 0.95 [0.91, 0.99]; P=0.008), CVD death (RR [95% CI]: 0.93 [0.88, 0.99]; P=0.013), and total CVD (RR [95% CI]: 0.97 [0.94, 0.99]; P=0.015). Inverse associations for all outcomes were strengthened after including REDUCE-IT while introducing statistically significant heterogeneity. Statistically significant linear dose–response relationships were found for total CVD and major vascular events in the analyses with and without including REDUCE-IT.
Conclusions-—Marine omega-3 supplementation lowers risk for myocardial infarction, CHD death, total CHD, CVD death, and total CVD, even after exclusion of REDUCE-IT. Risk reductions appeared to be linearly related to marine omega-3 dose. ( J Am Heart Assoc. 2019;8:e013543. DOI: 10.1161/JAHA.119.013543.)
https://www.ncbi.nlm.nih.gov/
Clinical Perspective What Is New?
- We updated previous meta-analyses by adding 3 recent large randomized controlled clinical trials, increasing sample size by 64%.
- Marine omega-3 supplementation significantly lowered risk for most cardiovascular end points, even after excluding a trial testing very high-dose supplementation.
- Risk reductions were linearly associated with dose of marine omega-3 supplementation.
What Are the Clinical Implications?
- Daily marine omega-3 supplementation is effective in lowering risk for coronary and most other cardiovascular end points, including myocardial infarction, coronary heart disease death, total coronary heart disease, cardiovascular disease death, and total cardiovascular disease; no benefits, however, were found for stroke.
- Greater cardiovascular benefits may be achieved at higher doses of marine omega- 3 supplementation.
Repair the Roof Before It Starts Raining…
The following is an article published in JAMA Neurology that highlights the need to consider vascular risk factors at a younger age to help prevent decline in brain volume and function later in life. Dementia risk in later life was more strongly associated with vascular risk factors in early adulthood versus later adulthood. Data from this study makes a strong case for addressing vascular risk factors as early as the fourth decade of life; strengthens the case for studying adolescent, early-childhood, and perinatal factors as factors associated with dementia; and warns that effective prevention of dementia in our time will likely require extending thinking well beyond the seductive amyloid hypothesis and the current emphasis on elderly patients as the best target for preventive interventions. Indeed, aging, successful or otherwise, involves many biological pathways and begins at birth.
November 4, 2019
Associations Between Vascular Risk Across Adulthood and Brain Pathology in Late Life
Evidence From a British Birth Cohort
Christopher A. Lane, MD, PhD1; Josephine Barnes, PhD1; Jennifer M. Nicholas, PhD1,2; et al Carole H. Sudre, PhD1,3; David M. Cash, PhD1; Ian B. Malone, PhD1; Thomas D. Parker, MRCP, PhD1; Ashvini Keshavan, MRCP, PhD1; Sarah M. Buchanan, FRACP1; Sarah E. Keuss, MRCP1; Sarah-Naomi James, PhD4; Kirsty Lu, MA1; Heidi Murray-Smith, MSc1; Andrew Wong, PhD4; Elizabeth Gordon, MSc1; William Coath, MSc1; Marc Modat, PhD1,3; David Thomas, PhD5,6; Marcus Richards, PhD4; Nick C. Fox, FMedSci1,7; Jonathan M. Schott, MD, FRCP1,7
Author Affiliations Article Information
JAMA Neurol. Published online November 4, 2019. doi: https://doi.org/10.1001/
Key Points
Question When is vascular risk during adulthood (early adulthood, midlife, or late life) most strongly associated with late-life brain structure and pathology?
Findings In a propective cohort of 463 participants free of dementia from the population-based Insight 46 study, higher vascular risk in early adulthood was most strongly associated with smaller whole-brain volumes and greater white matter–hyperintensity volumes at age 69 to 71 years. There were no associations at any age with amyloid status.
Meaning These findings are consistent with vascular risk influencing late-life brain health via cerebral small-vessel disease and lower brain volumes but not amyloidosis; vascular risk screening and modification may need to be considered from early adulthood.
Abstract
Importance Midlife vascular risk burden is associated with late-life dementia. Less is known about if and how risk exposure in early adulthood influences late-life brain health.
Objective To determine the associations between vascular risk in early adulthood, midlife, and late life with late-life brain structure and pathology using measures of white matter–hyperintensity volume, β-amyloid load, and whole-brain and hippocampal volumes.
Design, Setting, and Participants This prospective longitudinal cohort study, Insight 46, is part of the Medical Research Council National Survey of Health and Development, which commenced in 1946. Participants had vascular risk factors evaluated at ages 36 years (early adulthood), 53 years (midlife), and 69 years (early late life). Participants were assessed with multimodal magnetic resonance imaging and florbetapir-amyloid positron emission tomography scans between May 2015 and January 2018 at University College London. Participants with at least 1 available imaging measure, vascular risk measurements at 1 or more points, and no dementia were included in analyses.
Exposures Office-based Framingham Heart study–cardiovascular risk scores (FHS-CVS) were derived at ages 36, 53, and 69 years using systolic blood pressure, antihypertensive medication usage, smoking, diabetic status, and body mass index. Analysis models adjusted for age at imaging, sex, APOE genotype, socioeconomic position, and, where appropriate, total intracranial volume.
Main Outcomes and Measures White matter–hyperintensity volume was generated from T1/fluid-attenuated inversion recovery scans using an automated technique and whole-brain volume and hippocampal volume were generated from automated in-house pipelines; β-amyloid status was determined using a gray matter/eroded subcortical white matter standardized uptake value ratio threshold of 0.61.
Results A total of 502 participants were assessed as part of Insight 46, and 463 participants (236 male [51.0%]) with at least 1 available imaging measure (mean [SD] age at imaging, 70.7 [0.7] years; 83 β-amyloid positive [18.2%]) who fulfilled eligibility criteria were included. Among them, FHS-CVS increased with age (36 years: median [interquartile range], 2.7% [1.5%-3.6%]; 53 years: 10.9% [6.7%-15.6%]; 69 years: 24.3% [14.9%-34.9%]). At all points, these scores were associated with smaller whole-brain volumes (36 years: β coefficient per 1% increase, −3.6 [95% CI, −7.0 to −0.3]; 53 years: −0.8 [95% CI, −1.5 to −0.08]; 69 years: −0.6 [95% CI, −1.1 to −0.2]) and higher white matter–hyperintensity volume (exponentiated coefficient: 36 years, 1.09 [95% CI, 1.01-1.18]; 53 years, 1.02 [95% CI, 1.00-1.04]; 69 years, 1.01 [95% CI, 1.00-1.02]), with largest effect sizes at age 36 years. At no point were FHS-CVS results associated with β-amyloid status.
Conclusions and Relevance Higher vascular risk is associated with smaller whole-brain volume and greater white matter–hyperintensity volume at age 69 to 71 years, with the strongest association seen with early adulthood vascular risk. There was no evidence that higher vascular risk influences amyloid deposition, at least up to age 71 years. Reducing vascular risk with appropriate interventions should be considered from early adulthood to maximize late-life brain health.