Circulating Docosahexaenoic Acid and Risk of All-Cause and Cause-Specific Mortality.

OBJECTIVE: To assess the associations of docosahexaenoic acid (DHA), a marine omega-3 fatty acid, with long-term all-cause mortality, cardiovascular (CV) mortality, and cancer mortality. PATIENTS AND METHODS: We analyzed data from UK Biobank, which included 117,702 subjects with baseline plasma DHA levels and 12.7 years of follow-up between April 2007 and December 2021. Associations with risk for mortality endpoints were analyzed categorically by quintile of DHA plasma levels. RESULTS: Comparing the lowest to highest quintiles of circulating levels of DHA, there was 21% lower risk of all-cause mortality (HR, 0.79; 95% CI, 0.74 to 0.85; P<.0001). In a secondary analysis, we merged the UK Biobank findings with those from a recent FORCE (Fatty Acid and Outcome Research Consortium) meta-analysis that included 17 prospective cohort studies and 42,702 individuals examining DHA and mortality associations. The cumulative sample population included 160,404 individuals and 24,342 deaths during a median of 14 years of follow-up. After multivariable adjustment for relevant risk factors comparing the lowest to the highest quintiles of DHA, there was 17% lower risk of all-cause mortality (95% CI, 0.79 to 0.87; P<.0001), 21% lower risk for CV disease mortality (95% CI, 0.73 to 0.87; P<.001), 17% lower risk for cancer mortality (95% CI, 0.77 to 0.89; P<.0001), and 15% lower risk for all other mortality (95% CI, 0.79 to 0.91; P<.001). CONCLUSION: Higher DHA levels were associated with significant risk reductions in all-cause mortality, as well as reduced risks for deaths due to CV disease, cancer, and all other causes. The findings strengthen the hypothesis that DHA, a marine-sourced omega-3, may support CV health and lifespan.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

A Genome-Wide Interaction Study of Erythrocyte ω-3 Polyunsaturated Fatty Acid Species and Memory in the Framingham Heart Study Offspring Cohort.

BACKGROUND: Cognitive decline, and more specifically Alzheimer's disease, continues to increase in prevalence globally, with few, if any, adequate preventative approaches. Several tests of cognition are utilized in the diagnosis of cognitive decline that assess executive function, short- and long-term memory, cognitive flexibility, and speech and motor control. Recent studies have separately investigated the genetic component of both cognitive health, using these measures, and circulating fatty acids. OBJECTIVES: We aimed to examine the potential moderating effect of main species of ω-3 polyunsaturated fatty acids (PUFAs) on an individual's genetically conferred risk of cognitive decline. METHODS: The Offspring cohort from the Framingham Heart Study was cross-sectionally analyzed in this genome-wide interaction study (GWIS). Our sample included all individuals with red blood cell ω-3 PUFA, genetic, cognitive testing (via Trail Making Tests [TMTs]), and covariate data (N = 1620). We used linear mixed effects models to predict each of the 3 cognitive measures (TMT A, TMT B, and TMT D) by each ω-3 PUFA, single nucleotide polymorphism (SNP) (0, 1, or 2 minor alleles), ω-3 PUFA by SNP interaction term, and adjusting for sex, age, education, APOE ε4 genotype status, and kinship (relatedness). RESULTS: Our analysis identified 31 unique SNPs from 24 genes reaching an exploratory significance threshold of 1×10-5. Fourteen of the 24 genes have been previously associated with the brain/cognition, and 5 genes have been previously associated with circulating lipids. Importantly, 8 of the genes we identified, DAB1, SORCS2, SERINC5, OSBPL3, CPA6, DLG2, MUC19, and RGMA, have been associated with both cognition and circulating lipids. We identified 22 unique SNPs for which individuals with the minor alleles benefit substantially from increased ω-3 fatty acid concentrations and 9 unique SNPs for which the common homozygote benefits. CONCLUSIONS: In this GWIS of ω-3 PUFA species on cognitive outcomes, we identified 8 unique genes with plausible biology suggesting individuals with specific polymorphisms may have greater potential to benefit from increased ω-3 PUFA intake. Additional replication in prospective settings with more diverse samples is needed.

Genome-wide association studies and fine-mapping identify genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts.

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of P < 5 × 10-8, we confirmed association of the FADS signal and found evidence of two additional signals (in DAGLA and BEST1) within 200 kb of the originally reported FADS signal. Outside of the FADS region, we identified novel signals for arachidonic acid (AA) in Hispanic Americans located in/near genes including TMX2, SLC29A2, ANKRD13D and POLD4, and spanning a > 9 Mb region on chromosome 11 (57.5 Mb ~ 67.1 Mb). Among these novel signals, we found associations unique to Hispanic Americans, including rs28364240, a POLD4 missense variant for AA that is common in CHARGE Hispanic Americans but absent in other race/ancestry groups. Our study sheds light on the genetics of PUFAs and the value of investigating complex trait genetics across diverse ancestry populations.

Association between blood N-3 fatty acid levels and the risk of coronavirus disease 2019 in the UK Biobank.

BACKGROUND: The role of nutritional status and the risk of contracting and/or experiencing adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unclear. Preliminary studies suggest that higher n-3 PUFA intakes are protective. OBJECTIVES: This study aimed to compare the risk of 3 coronavirus disease 2019 (COVID-19) outcomes (testing positive for SARS-CoV-2, hospitalization, and death) as a function of the baseline plasma DHA levels. METHODS: The DHA levels (% of total fatty acids [FAs]) were measured by nuclear magnetic resonance. The 3 outcomes and relevant covariates were available for 110,584 subjects (hospitalization and death) and for 26,595 ever-tested subjects (positive for SARS-CoV-2) in the UK Biobank prospective cohort study. Outcome data between 1 January, 2020, and 23 March, 2021, were included. The Omega-3 Index (O3I) (RBC EPA + DHA%) values across DHA% quintiles were estimated. The multivariable Cox proportional hazards models were constructed, and linear (per 1 SD) relations with the risk of each outcome were computed as HRs. RESULTS: In the fully adjusted models, comparing the fifth to the first DHA% quintiles, the HRs (95% confidence intervals) for testing positive, being hospitalized, and dying with COVID-19 were 0.79 (0.71, 0.89, P < 0.001), 0.74 (0.58, 0.94, P < 0.05), and 1.04 (0.69-1.57, not significant), respectively. On a per 1-SD increase in DHA% basis, the HRs for testing positive, hospitalization, and death, were 0.92 (0.89, 0.96, P < 0.001), 0.89 (0.83, 0.97, P < 0.01), and 0.95 (0.83, 1.09), respectively. The estimated O3I values across DHA quintiles ranged from 3.5% (quintile 1) to 8% (quintile 5). CONCLUSIONS: These findings suggest that nutritional strategies to increase the circulating n-3 PUFA levels, such as increased consumption of oily fish and/or use of n-3 FA supplements, may reduce the risk of adverse COVID-19 outcomes.

Lower omega-3 status associated with higher erythrocyte distribution width and neutrophil-lymphocyte ratio in UK Biobank cohort.

High red blood distribution width (RDW) is associated with decreased red blood cell deformability, and high neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and innate-adaptive immune system imbalance. Both RDW and NLR are predictors of chronic disease risk and mortality. Omega-3 index (O3I) values have previously been shown to be inversely associated with RDW and NLR levels. Our objective was to determine if total plasma long chain omega-3 fatty acids (Omega3%) measured in the UK Biobank cohort were associated with RDW and NLR values. RDW- and NLR- relationships with Omega3% were characterized in 109,191 adults (58.4% female). RDW- and NLR-Omega3% relationships were inversely associated with Omega3% (both p < 0.0001). These cross-sectional associations confirm previous findings that increasing RDW and NLR values are associated with low O3I. The hypothesis that RDW and/or NLR values can be reduced in individuals with less-than optimal long chain omega 3 values need to be tested in randomized controlled intervention trials using EPA and/or DHA.

Multimarker omnibus tests by leveraging individual marker summary statistics from large biobanks.

As biobanks become increasingly popular, access to genotypic and phenotypic data continues to increase in the form of precomputed summary statistics (PCSS). Widespread accessibility of PCSS alleviates many issues related to biobank data, including that of data privacy and confidentiality, as well as high computational costs. However, questions remain about how to maximally leverage PCSS for downstream statistical analyses. Here we present a novel method for testing the association of an arbitrary number of single nucleotide variants (SNVs) on a linear combination of phenotypes after adjusting for covariates for common multimarker tests (e.g., SKAT, SKAT-O) without access to individual patient-level data (IPD). We validate exact formulas for each method, and demonstrate their accuracy through simulation studies and an application to fatty acid phenotypic data from the Framingham Heart Study.

Reliability and Validity of the State-Trait Hopelessness Scale in a Primarily Rural Population of Adults With Ischemic Heart Disease in the US Great Plains.

PURPOSE: Hopelessness and rurality are each independently associated with increased mortality in adults with ischemic heart disease (IHD), yet there is no known research examining hopelessness in rural patients with IHD. The authors of this study evaluated the reliability and validity of the State-Trait Hopelessness Scale (STHS) in a primarily rural population of adults with IHD living in West North Central United States (US Great Plains). METHODS: Reliability, concurrent validity, and convergent validity were evaluated for 115 adults hospitalized for IHD. Rural-Urban Commuting Area codes were used to stratify participants by rurality level, with 66% categorized as rural. Principal component analysis was used to examine potential factor structure of the STHS. FINDINGS: Cronbach α for the State and Trait Hopelessness subscales were 0.884 and 0.903, respectively. Concurrent validity was supported for the State and Trait subscales using the Patient Health Questionnaire-8 (State: r = 0.50, P < .001; Trait: r = 0.35, P < .001). Convergent validity was supported for the State subscale using the Duke Activity Status Index ( r = -0.23, P = .013). Principal component analysis showed 2 factors (hopelessness present and hopelessness absent) for the State and Trait subscales, accounting for 63% and 58% of variance, respectively. CONCLUSIONS: Findings support the reliability and validity of the STHS for evaluation of hopelessness in rural adults with IHD in clinical and research settings. Results replicated the same factor structure found in testing of the STHS in a primarily urban sample. Because of the prevalence of hopelessness in rural adults with IHD and association with increased mortality, hopelessness should be assessed during hospitalization and in the recovery period.

Association between Omega-3 Index and Hyperglycemia Depending on Body Mass Index among Adults in the United States.

There is inconsistency regarding the association between long-chain n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA; 20:5n3) and docosahexaenoic acid (DHA; 22:6n3) and the risk of type 2 diabetes. The present study aimed to investigate the association between the Omega-3 Index (erythrocyte EPA + DHA) and glycemic status as a function of body mass index (BMI). Cross-sectional data from routine clinical laboratory testing with a total of 100,572 people aged over 18 years and BMI ≥ 18.5 kg/m2 were included. Of the patients, 10% were hyperglycemic (fasting plasma glucose levels ≥ 126 mg/dL) and 24.7% were of normal weight, 35.0% were overweight, and 40.3% were obese. Odds ratios (ORs) of being hyperglycemic were inversely associated with the Omega-3 Index, but weakened as BMI increased. Thus, ORs (95% CI) comparing quintile 5 with quintile 1 were 0.54 (0.44-0.66) in the normal weight group, 0.70 (0.61-0.79) in the overweight group, and 0.74 (0.67-0.81) in the obese group. Similar patterns were seen for EPA and DHA separately. The present study suggested that a low Omega-3 Index is associated with a greater risk of disordered glucose metabolism and this is independent of BMI.

The Omega-3 Index is higher in people from a coastal town versus 5 inland US cities: An observational study.

Higher omega-3 fatty acid blood levels, as assessed by the Omega-3 Index (O3I, erythrocyte eicosapentaenoic [EPA] + docosahexaenoic [DHA] percentage), have been linked with lower risk for cardiovascular disease and total mortality. Because seafood is an excellent source of EPA and DHA, we reasoned that people living on the coast with direct access to fresh seafood might have higher O3I levels than people living inland. Using O3I data originally collected for other purposes and an observational design, we compared the mean O3I from people in Newport, RI, with that of people living from 5 inland US cities (Indianapolis, IN; Charleston, WV; Lexington, KY; Oklahoma City, OK; and Memphis, TN). The Newport samples were collected at free, industry-sponsored health fairs, whereas the inland city samples were collected at free public health screenings sponsored by the Seafood Nutrition Partnership in 2014 through 2015. The mean (standard deviation) O3I in the Newport sample (n = 226) was 5.13% (1.34%) and the mean of the 5 cities (n = 1109) was 4.48% (1.08%) (P < .001). An O3I of ≥8% (considered optimal) was found in 3% of the Newport sample and in 1% of the pooled inland cities (P < .05). An O3I of ≤4% (considered low) was found in 22% of the Newport sample and in 41% of the pooled inland cities (P < .001). These data support our hypothesis, but because only 3% of those in the Newport sample had an O3I >8%, even greater seafood intake (or the use of fortified foods or dietary supplements) is needed to attain optimal omega-3 status.

The omega-3 index is inversely associated with the neutrophil-lymphocyte ratio in adults'.

The neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and measures innate-adaptive immune system balance. The omega-3-index (O3I) measures the amount of EPA+DHA in blood. Both a low O3I and an elevated NLR are associated with increased risk for chronic disease and mortality, including cardiovascular diseases and cancer. Hypothesizing that low O3I may partly contribute to systemic chronic inflammation, we asked if a relationship existed between O3I and NLR in healthy adults (≥18 y, n = 28,871, 51% female) without inflammation [C-reactive protein (CRP) <3 mg/mL)] who underwent a routine clinical assessment. NLR was inversely associated with O3I before (p < 0.0001) and after adjusting for age, sex, BMI, and CRP (p < 0.0001). Pearson correlations of other variables with NLR were r = 0.06 (CRP), r = 0.14 (age), and r = 0.01(BMI). In this healthy population, an O3I < 6.6% was associated with increasing NLR whereas NLR remained relatively constant (low) when O3I > 6.6%, suggestive of a quiescent, balanced immune system.

Omega-3 index is directly associated with a healthy red blood cell distribution width.

Low red blood cell (RBC) membrane content of EPA and DHA, i.e., the omega-3 index (O3I), and elevated RBC distribution width (RDW) are risk factors for all-cause mortality. O3I and RDW are related with membrane fluidity and deformability. Our objective was to determine if there is a relationship between O3I and RDW in healthy adults. Subjects without inflammation or anemia, and with values for O3I, RDW, high-sensitivity C-reactive protein (CRP), body mass index (BMI), age and sex were identified (n = 25,485) from a clinical laboratory dataset of  > 45,000 individuals. RDW was inversely associated with O3I in both sexes before and after (both p < 0.00001) adjusting models for sex, age, BMI and CRP. Stratification by sex revealed a sex-O3I interaction with the RDW-O3I slope (p < 0.00066) being especially steep in females with O3I ≤ 5.6%. In healthy adults of both sexes, the data suggested that an O3I of > 5.6% may help maintain normal RBC structural and functional integrity.

Investigating Rurality as a Risk Factor for State and Trait Hopelessness in Hospitalized Patients With Ischemic Heart Disease.

Background Rurality and hopelessness are each associated with increased mortality in adults with ischemic heart disease (IHD), yet there is no known research examining rurality as a risk factor for hopelessness in patients with IHD. This study evaluated rurality as a risk factor for state and trait hopelessness in adults hospitalized with IHD in samples drawn from the Great Lakes and Great Plains regions of the United States. Methods and Results A descriptive cross-sectional design was used. Data were collected from 628 patients hospitalized for IHD in the Great Lakes (n=516) and Great Plains (n=112). Rural-Urban Commuting Area codes were used to stratify study participants by level of rurality. Levels of state hopelessness (measured by the State-Trait Hopelessness Scale) were higher in rural patients (58.8% versus 48.8%; odds ratio [OR], 1.50; 95% CI, 1.03-2.18), a difference that remained statistically significant after adjusting for demographics, depression severity (measured by the Patient Health Questionnaire-8), and physical functioning (measured by the Duke Activity Status Index; OR, 1.59; 95% CI, 1.06-2.40; P=0.026). There was evidence of an interaction between marital status and rurality on state hopelessness after accounting for covariates (P=0.02). Nonmarried individuals had an increased prevalence of state hopelessness (nonmarried 72.0% versus married 52.0%) in rural areas (P=0.03). Conclusions Rural patients with IHD, particularly those who are nonmarried, may be at higher risk for state hopelessness compared with patients with IHD living in urban settings. Understanding rurality differences is important in identifying subgroups most at risk for hopelessness. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT04498975.

Using an erythrocyte fatty acid fingerprint to predict risk of all-cause mortality: the Framingham Offspring Cohort.

BACKGROUND: RBC long-chain omega-3 (n-3) fatty acid (FA) percentages (of total fatty acids) are associated with lower risk for total mortality, but it is unknown if a suite of FAs could improve risk prediction. OBJECTIVES: The objective of this study was to compare a combination of RBC FA levels with standard risk factors for cardiovascular disease (CVD) in predicting risk of all-cause mortality. METHODS: Framingham Offspring Cohort participants without prevalent CVD having RBC FA measurements and relevant baseline clinical covariates (n = 2240) were evaluated during 11 y of follow-up. A forward, stepwise approach was used to systematically evaluate the association of 8 standard risk factors (age, sex, total cholesterol, HDL cholesterol, hypertension treatment, systolic blood pressure, smoking status, and prevalent diabetes) and 28 FA metrics with all-cause mortality. A 10-fold cross-validation process was used to build and validate models adjusted for age and sex. RESULTS: Four of 28 FA metrics [14:0, 16:1n-7, 22:0, and omega-3 index (O3I; 20:5n-3 + 22:6n-3)] appeared in ≥5 of the discovery models as significant predictors of all-cause mortality. In age- and sex-adjusted models, a model with 4 FA metrics was at least as good at predicting all-cause mortality as a model including the remaining 6 standard risk factors (C-statistic: 0.778; 95% CI: 0.759, 0.797; compared with C-statistic: 0.777; 95% CI: 0.753, 0.802). A model with 4 FA metrics plus smoking and diabetes (FA + Sm + D) had a higher C-statistic (0.790; 95% CI: 0.770, 0.811) compared with the FA (P < 0.01) or Sm + D models alone (C-statistic: 0.766; 95% CI: 0.739, 0.794; P < 0.001). A variety of other highly correlated FAs could be substituted for 14:0, 16:1n-7, 22:0, or O3I with similar predicted outcomes. CONCLUSIONS: In this community-based population in their mid-60s, RBC FA patterns were as predictive of risk for death during the next 11 y as standard risk factors. Replication is needed in other cohorts to validate this FA fingerprint as a predictor of all-cause mortality.

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Effects of menopausal hormone therapy on erythrocyte n-3 and n-6 PUFA concentrations in the Women's Health Initiative randomized trial.

BACKGROUND: The factors other than dietary intake that determine tissue concentrations of EPA and DHA remain obscure. Prior studies suggested that, in women, endogenous estrogen may accelerate synthesis of DHA from ɑ-linolenic acid (ALA), but the effects of exogenous estrogen on RBC n-3 (É·-3) PUFA concentrations are unknown. OBJECTIVE: We tested the hypothesis that menopausal hormone therapy (HT) would increase RBC n-3 PUFA concentrations. METHODS: Postmenopausal women (ages 50-79 y) were assigned to HT or placebo in the Women's Health Initiative (WHI) randomized trial. The present analyses included a subset of 1170 women (ages 65-79 y) who had RBC PUFA concentrations measured at baseline and at 1 y as participants in the WHI Memory Study. HT included conjugated equine estrogens (E) alone for women without a uterus (n = 560) and E plus medroxyprogesterone acetate (P) for those with an intact uterus (n = 610). RBC n-3 and n-6 (É·-6) PUFAs were quantified. RESULTS: Effects of E alone and E+P on PUFA profiles were similar and were thus combined in the analyses. Relative to the changes in the placebo group after 1 y of HT, docosapentaenoic acid (DPA; n-3) concentrations decreased by 10% (95% CI: 7.3%, 12.5%), whereas DHA increased by 11% (95% CI: 7.4%, 13.9%) in the HT group. Like DHA, DPA n-6 increased by 13% from baseline (95% CI: 10.0%, 20.3%), whereas linoleic acid decreased by 2.0% (95% CI: 1.0%, 4.1%; P values at least <0.01 for all). EPA and arachidonic acid concentrations were unchanged. CONCLUSIONS: HT increased RBC concentrations of the terminal n-3 and n-6 PUFAs (DHA and DPA n-6). These findings are consistent with an estrogen-induced increase in DHA and DPA n-6 synthesis, which is consistent with an upregulation of fatty acid elongases and/or desaturases in the PUFA synthetic pathway. The clinical implications of these changes require further study. The Women's Health Initiative Memory Study is registered at clinicaltrials.gov as NCT00685009. Note that the data presented here were not planned as part of the original trial, and therefore are to be considered exploratory.

Association of the Omega-3 Index with Incident Prostate Cancer with Updated Meta-Analysis: The Cooper Center Longitudinal Study.

BACKGROUND: The association between long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and prostate cancer (PC) remains unclear. METHODS: We compared incident PC rates as a function of the Omega-3 Index [O3I, erythrocyte eicosapentaenoic and docosahexaenoic acids (EPA + DHA)] in 5607 men (40-80 years of age) seen at the Cooper Clinic who were free of PC at baseline. The average follow-up was 5.1 ± 2.8 years until censoring or reporting a new PC diagnosis. Proportional hazards regression was used to model the linear association between baseline O3I and the age-adjusted time to diagnosis. A meta-analysis of n-3 PUFA biomarker-based studies and incident PC was updated with the present findings. RESULTS: A total of 116 cases of incident PC were identified. When O3I was examined as a continuous variable, the age-adjusted hazard ratio (HR) (95% CI) was 0.98 (0.89, 1.07; p = 0.25) for each 1% increment in the O3I. The updated meta-analysis with 10 biomarker-based studies found no significant relationship between EPA or DHA levels and risk for PC. CONCLUSIONS: We find no evidence in this study nor in a meta-analysis of similar studies that consuming n-3 PUFA-rich fish or using fish oil supplements affects the risk of PC.

Heart up! RCT protocol to increase physical activity in cardiac patients who report hopelessness: Amended for the COVID-19 pandemic.

Hopelessness is associated with decreased physical activity (PA) and increased adverse events and death in patients with ischemic heart disease (IHD). Rates of PA in patients with IHD continue to be low in both hospital-based cardiac rehabilitation and home settings. While researchers have investigated strategies to increase PA among patients with IHD, interventions to promote PA specifically in IHD patients who report hopelessness are lacking. We describe the protocol for a NIH-funded randomized controlled trial designed to establish the effectiveness of a 6-week intervention (Heart Up!) to promote increased PA in IHD patients who report hopelessness. Participants (n = 225) are randomized to one of three groups: (1) motivational social support (MSS) from a nurse, (2) MSS from a nurse plus significant other support (SOS), or (3) attention control. Aims are to: (1) test the effectiveness of 6 weeks of MSS and MSS with SOS on increasing mean minutes per day of moderate to vigorous PA; (2) determine the effects of change in moderate to vigorous PA on hopelessness; and (3) determine if perceived social support and motivation (exercise self-regulation) mediate the effects of the intervention on PA. A total of 69 participants have been enrolled to date. The protocol has been consistently and accurately used by research personnel. We address the protocol challenges presented by the COVID-19 pandemic and steps taken to maintain fidelity to the intervention. Findings from this study could transform care for IHD patients who report hopelessness by promoting self-management of important PA goals that can contribute to better health outcomes.

Blood omega-3 fatty acids and death from COVID-19: A pilot study.

Very-long chain omega-3 fatty acids (EPA and DHA) have anti-inflammatory properties that may help reduce morbidity and mortality from COVID-19 infection. We conducted a pilot study in 100 patients to test the hypothesis that RBC EPA+DHA levels (the Omega-3 Index, O3I) would be inversely associated with risk for death by analyzing the O3I in banked blood samples drawn at hospital admission. Fourteen patients died, one of 25 in quartile 4 (Q4) (O3I ≥5.7%) and 13 of 75 in Q1-3. After adjusting for age and sex, the odds ratio for death in patients with an O3I in Q4 vs Q1-3 was 0.25, p = 0.07. Although not meeting the classical criteria for statistical significance, this strong trend suggests that a relationship may indeed exist, but more well-powered studies are clearly needed.