Abstract MP35: Association Of Orthostatic Blood Pressure Response With Incident Heart Failure: The Framingham Heart Study

Introduction: Orthostatic hypotension (OH) and hypertension (OHT) are associated with cardiovascular disease and mortality. The relation of OH and OHT with heart failure (HF) in the community is not well explored, particularly among the elderly and those with hypertension. Moreover, there remains a paucity of longitudinal data on the development of HF subtypes (HF with reduced ejection fraction [HFrEF] and HF with preserved ejection fraction [HFpEF]) in those with OH and OHT. Hypothesis: We hypothesized that OH and OHT are associated with a higher risk of HF. Methods: We evaluated 1914 Framingham Heart Study participants (mean age 72 years, 1159 women [61%]), with available orthostatic blood pressure (BP) measurements. OH was defined as a decrease and OHT as an increase of 20/10 mmHg in systolic/diastolic BP from supine to standing position, respectively. We used a categorical variable (OH, OHT, absence of OH and OHT [referent]). Using Cox proportional hazards regression, we related OH and OHT to risk of HF and its subtypes (HFrEF, HFpEF), compared to the referent group, adjusting for age, sex, body mass index, systolic BP, diastolic BP, hypertension treatment, smoking, and diabetes. Results: There were 275 participants with OH (181 women, 66%) and 411 with OHT (236 women, 57%). On median follow-up of 13 years, 492 developed HF (292 women, 59%). In multivariable-adjusted analyses, OH was associated with higher risk of HF (Hazards Ratio [HR] 1.47; 95% CI, 1.13-1.92; Figure ) compared to referent. Further, OH was associated with higher risk of HFrEF (HR 2.56; 95% CI, 1.46-4.48), but not HFpEF. OHT was not associated with incident HF. Conclusions: Assessment of orthostatic BP response in the elderly may identify future HF risk. Further studies are warranted to investigate mechanisms underlying the observed associations.

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Association of Blood Pressure and Heart Rate Responses to Submaximal Exercise With Incident Heart Failure: The Framingham Heart Study

Journal of the American Heart Association ◽

10.1161/jaha.120.019460 ◽

2021 ◽

Author(s):

Herman A. Carneiro ◽

Rebecca J. Song ◽

Joowon Lee ◽

Brian Schwartz ◽

Ramachandran S. Vasan ◽

...

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Heart Rate ◽

Ejection Fraction ◽

Pulse Pressure ◽

Framingham Heart Study ◽

Submaximal Exercise ◽

Exercise Stress ◽

Reduced Ejection Fraction ◽

Heart Study

Background Exercise stress tests are conventionally performed to assess risk of coronary artery disease. Using the FHS (Framingham Heart Study) Offspring cohort, we related blood pressure (BP) and heart rate responses during and after submaximal exercise to the incidence of heart failure (HF). Methods and Results We evaluated Framingham Offspring Study participants (n=2066; mean age, 58 years; 53% women) who completed 2 stages of an exercise test (Bruce protocol) at their seventh examination (1998–2002). We measured pulse pressure, systolic BP, diastolic BP, and heart rate responses during stage 2 exercise (2.5 mph at 12% grade). We calculated the changes in systolic BP, diastolic BP, and heart rate from stage 2 to recovery 3 minutes after exercise. We used Cox proportional hazards regression to relate each standardized exercise variable (during stage 2, and at 3 minutes of recovery) individually to HF incidence, adjusting for standard risk factors. On follow‐up (median, 16.8 years), 85 participants developed new‐onset HF. Higher exercise diastolic BP was associated with higher HF with reduced ejection fraction (ejection fraction <50%) risk (hazard ratio [HR] per SD increment, 1.26; 95% CI, 1.01–1.59). Lower stage 2 pulse pressure and rapid postexercise recovery of heart rate and systolic BP were associated with higher HF with reduced ejection fraction risk (HR per SD increment, 0.73 [95% CI, 0.57–0.94]; 0.52 [95% CI, 0.35–0.76]; and 0.63 [95% CI, 0.47–0.84], respectively). BP and heart rate responses to submaximal exercise were not associated with risk of HF with preserved ejection fraction (ejection fraction ≥50%). Conclusions Accentuated diastolic BP during exercise with slower systolic BP and heart rate recovery after exercise are markers of HF with reduced ejection fraction risk.

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Association of physical activity and heart failure with preserved vs. reduced ejection fraction in the elderly: the Framingham Heart Study

European Journal of Heart Failure ◽

10.1093/eurjhf/hft025 ◽

2013 ◽

Vol 15 (7) ◽

pp. 742-746 ◽

Cited By ~ 57

Author(s):

Elisabeth Kraigher-Krainer ◽

Asya Lyass ◽

Joseph M. Massaro ◽

Douglas S. Lee ◽

Jennifer E. Ho ◽

...

Keyword(s):

Physical Activity ◽

Heart Failure ◽

Ejection Fraction ◽

Framingham Heart Study ◽

The Elderly ◽

Reduced Ejection Fraction ◽

Heart Study

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Blood Pressure and Safety Events With Vericiguat in the VICTORIA Trial

Journal of the American Heart Association ◽

10.1161/jaha.121.021094 ◽

2021 ◽

Author(s):

Carolyn S. P. Lam ◽

Hillary Mulder ◽

Yuri Lopatin ◽

Jose B. Vazquez‐Tanus ◽

David Siu ◽

...

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Ejection Fraction ◽

Proportional Hazards ◽

Study Drug ◽

Cox Proportional Hazards ◽

Angiotensin Receptor ◽

Unique Identifier ◽

Reduced Ejection Fraction ◽

Over Time

Background Although safety and tolerability of vericiguat were established in the VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial in patients with heart failure with reduced ejection fraction, some subgroups may be more susceptible to symptomatic hypotension, such as older patients, those with lower baseline systolic blood pressure (SBP), or those concurrently taking angiotensin receptor neprilysin inhibitors. We described the SBP trajectories over time and compared the occurrence of symptomatic hypotension or syncope by treatment arm in potentially vulnerable subgroups in VICTORIA. We also evaluated the relation between the efficacy of vericiguat and baseline SBP. Methods and Results Among patients receiving at least 1 dose of the study drug (n=5034), potentially vulnerable subgroups were those >75 years old (n=1395), those with baseline SBP 100–110 mm Hg (n=1344), and those taking angiotensin receptor neprilysin inhibitors (n=730). SBP trajectory was plotted as mean change from baseline over time. The treatment effect on time to symptomatic hypotension or syncope was evaluated overall and by subgroup, and the primary efficacy composite outcome (heart failure hospitalization or cardiovascular death) across baseline SBP was examined using Cox proportional hazards models. SBP trajectories showed a small initial decline in SBP with vericiguat in those >75 years old (versus younger patients), as well as those receiving angiotensin receptor neprilysin inhibitors (versus none), with SBP returning to baseline thereafter. Patients with SBP <110 mm Hg at baseline showed a trend to increasing SBP over time, which was similar in both treatment arms. Safety event rates were generally low and similar between treatment arms within each subgroup. In Cox proportional hazards analysis, there were similar numbers of safety events with vericiguat versus placebo (adjusted hazard ratio [HR], 1.18; 95% CI, 0.99–1.39; P =0.059). No difference existed between treatment arms in landmark analysis beginning after the titration phase (ie, post 4 weeks) (adjusted HR, 1.14; 95% CI, 0.93–1.38; P =0.20). The benefit of vericiguat compared with placebo on the primary composite efficacy outcome was similar across the spectrum of baseline SBP ( P for interaction=0.32). Conclusions These data demonstrate the safety of vericiguat in a broad population of patients with worsening heart failure with reduced ejection fraction, even among those predisposed to hypotension. Vericiguat’s efficacy persisted regardless of baseline SBP. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02861534.

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Целевой уровень артериального давления при лечении артериальной гипертензии у пациентов пожилого возраста с хронической сердечной недостаточностью

Kardiologicheskii vestnik ◽

10.36396/ms.2019.14.03.002 ◽

2019 ◽

pp. 8-16

Author(s):

M.S. CHERNIAEVA ◽

O.D. OSTROUMOVA

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Ejection Fraction ◽

Elderly Patients ◽

Cardiovascular Events ◽

The Elderly ◽

Target Blood Pressure ◽

Lower Systolic Blood Pressure ◽

Reduced Ejection Fraction ◽

Increased Risk

Высокая распространенность хронической сердечной недостаточности (ХСН) в популяции пожилых пациентов наряду с устойчивым ро- стом численности пожилого населения как в России, так и в западных странах все больше привлекает внимание врачей к проблеме, связан- ной с ведением данного заболевания. Известно, что ведущим фактором риска развития ХСН является повышенное артериальное давление (АД) и большинство пациентов с ХСН имеют в анамнезе артериальную гипертонию (АГ), поэтому лечение пациентов пожилого возраста c АГ и ХСН является одним из важных направлений в профилактике прогрессирования ХСН, снижения количества госпитализаций и смерт- ности. Лечение АГ у пожилых имеет свои особенности, связанные с функциональным статусом пациентов и их способностью переносить лечение. В европейских рекомендациях (2018) пересмотрены целевые цифры АД при лечении АГ у пожилых, однако данные по целевым цифрам АД для лечения АГ у пациентов с ХСН опираются лишь на исследования, проводившиеся у больных без ХСН. Данные об оптималь- ном целевом уровне у пациентов с АГ и ХСН представлены в единичных исследованиях. В настоящей статье проанализирована взаимосвязь уровня АД и сердечно-сосудистых событий и смертности отдельно для пациентов с АГ и сердечной недостаточностью с низкой фракцией выброса левого желудочка и с сохраненной фракцией выброса левого желудочка. Результаты многих исследований показывают, что более низкий уровень систолического АД (120 мм рт. ст.) и диастолического АД (80 мм рт. ст.) ассоциирован с развитием неблагоприятных сердечно-сосудистых событий, особенно у пациентов с сердечной недостаточностью с низкой фракцией выброса левого желудочка.The high prevalence of chronic heart failure (CHF) in the elderly patients, along with the steady growth of the elderly population, both in Russia and in Western countries, is increasingly attracting the attention of doctors to the problem associated with the management of this disease. It is known that the leading risk factor for CHF is high blood pressure (BP) and most patients with CHF have a history of hypertension (H), so the treatment of elderly patients with H and CHF is the major focus in the slowing CHF progression, reducing the heart failure hospitalisation and mortality. Treatment of hypertension in the elderly has some specific features associated with the functional status of patients and their ability to tolerate treatment. The European recommendations (2018) revised target blood pressure levels in the elderly patients, however, data on target blood pressure levels in patients with CHF are based only on studies conducted in patients without CHF, data on the optimal target blood pressure levels in patients with hypertension and CHF are presented in single studies. In this article we analyze the relationship between blood pressure levels and cardiovascular events and mortality separately for patients with hypertension and heart failure with reduced ejection fraction and with preserved ejection fraction. Several studies show that lower systolic blood pressure (120 mm Hg) and diastolic blood pressure (80 mm Hg) is associated with the increased risk of cardiovascular events, especially in patients with heart failure with reduced ejection fraction.

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P1666Do beta-blockers increase the risk for hospitalizations in heart failure with preserved ejection fraction? A secondary analysis of beta-blocker use in the TOPCAT trial

European Heart Journal ◽

10.1093/eurheartj/ehz748.0424 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

D N Silverman ◽

T B Plante ◽

M I Infeld ◽

S P Juraschek ◽

G Dougherty ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Beta Blocker ◽

Proportional Hazards ◽

Beta Blockers ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Reduced Ejection Fraction

Abstract Background The use of beta-blockers for treatment of heart failure (HF) with a reduced ejection fraction (EF) is unequivocally beneficial, but their role in the treatment of preserved EF (HFpEF) remains unclear. Purpose In a contemporary HFpEF cohort, we sought to assess the association of HF hospitalizations and the use of beta-blockers in patients with an EF above and below 50%. Methods The TOPCAT trial tested spironolactone vs. placebo among patients with HFpEF, including some with mild reductions in EF between 45–50%. The primary outcome was a composite of cardiovascular (CV) mortality, aborted cardiac arrest, or HF hospitalizations. Medication use, including beta-blockers, was reported at each visit and hospitalization. In the 1,761 participants from the Americas, we compared the association of beta-blocker use (vs. no use) and HF hospitalization or CV mortality using Cox proportional hazards models adjusted for baseline demographics, history of myocardial infarction, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and hypertension. The analyses were repeated in the EF strata ≥50% and <50%. Results Among patients included in the current analysis (mean age 72 years, 50% female, 78% white), 1,496/1,761 (85%) received beta-blockers and 1,566/1,761 (89%) had an EF ≥50%. HF hospitalizations and CV mortality occurred in 399/1,761 (23%) and 223/1,761 (13%) of participants, respectively. Beta-blocker use was associated with an increase in risk of HF hospitalization among patients with preserved EF ≥50% [HR 1.56, (95% CI 1.09–2.24), p=0.01] and was associated with a reduction in risk of hospitalization in patients with an EF <50% [HR 0.42, (95% CI 0.18- 0.99), p<0.05]. We found a significant interaction for EF threshold and beta-blocker use on incident HF hospitalizations (p=0.01). There were no differences in CV mortality. Figure 1. Kaplan Meier incidence plots Conclusions Beta-blocker use was associated with an increase in HF hospitalizations in patients with HFpEF (EF≥50%) but did not affect CV mortality. Further research is needed to confirm these findings and elucidate causality.

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Cardiovascular health, genetic risk, and risk of dementia in the Framingham Heart Study

Neurology ◽

10.1212/wnl.0000000000010306 ◽

2020 ◽

Vol 95 (10) ◽

pp. e1341-e1350 ◽

Cited By ~ 3

Author(s):

Gina M. Peloso ◽

Alexa S. Beiser ◽

Claudia L. Satizabal ◽

Vanessa Xanthakis ◽

Ramachandran S. Vasan ◽

...

Keyword(s):

Genetic Risk ◽

Framingham Heart Study ◽

Cardiovascular Health ◽

Proportional Hazards ◽

Genetic Risk Score ◽

Cox Proportional Hazards ◽

Ideal Cardiovascular Health ◽

Heart Study ◽

Common Genetic Variants ◽

Ε4 Allele

ObjectiveTo determine the joint role of ideal cardiovascular health (CVH) and genetic risk on risk of dementia.MethodsWe categorized CVH on the basis of the American Heart Association Ideal CVH Index and genetic risk through a genetic risk score (GRS) of common genetic variants and the APOE ε4 genotype in 1,211 Framingham Heart Study (FHS) offspring cohort participants. We used multivariable Cox proportional hazards regression models to examine the association between CVH, genetic risk, and incident all-cause dementia with up to 10 years of follow-up (mean 8.4 years, 96 incident dementia cases), adjusting for age, sex, and education.ResultsWe observed that a high GRS (>80th percentile) was associated with a 2.6-fold risk of dementia (95% confidence interval [CI] of hazard ratio [HR] 1.23–5.29; p = 0.012) compared with having a low GRS (<20th percentile); carrying at least 1 APOE ε4 allele was associated with a 2.3-fold risk of dementia compared with not carrying an APOE ε4 allele (95% CI of HR 1.49–3.53; p = 0.0002), and having a favorable CVH showed a 0.45-fold lower risk of dementia (95% CI of HR 0.20–1.01; p = 0.0527) compared to having an unfavorable CVH when all 3 components were included in the model. We did not observe an interaction between CVH and GRS (p = 0.99) or APOE ε4 (p = 0.16).ConclusionsWe observed that both genetic risk and CVH contribute additively to dementia risk.

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P57262018 ESC/ESH guideline-recommended age categories and intensive blood pressure management in high-risk adults: insights from SPRINT

European Heart Journal ◽

10.1093/eurheartj/ehz746.0666 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M Pareek ◽

T Biering-Sorensen ◽

M Vaduganathan ◽

C Byrne ◽

A Qamar ◽

...

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

European Society ◽

Proportional Hazards ◽

Controlled Trial ◽

Cox Proportional Hazards ◽

Standard Group ◽

Primary Efficacy ◽

Serious Adverse Events ◽

Similar Treatment

Abstract Background The 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines for arterial hypertension propose different intensities of blood pressure (BP) lowering in patients <65 years, 65–79 years, and ≥80 years of age. However, it is unclear whether intensive BP management is well-tolerated and modifies risk uniformly across this age spectrum. Purpose To assess the relationship between age, treatment response to intensive BP lowering, and cardiovascular (CV) outcomes. Methods SPRINT was a randomized, controlled trial in which 9,361 individuals ≥50 years of age, at high CV risk but without diabetes who had a systolic BP (SBP) 130–180 mmHg, were randomized to intensive (target SBP <120mmHg) or standard antihypertensive treatment (target SBP <140mmHg). The primary efficacy endpoint was the composite of acute coronary syndromes, stroke, heart failure, or death from CV causes. The primary safety endpoint was the composite of serious adverse events (SAE). We examined the prognostic implications of age, using Cox proportional-hazards regression models adjusted for demographic, clinical, and laboratory variables. Whether a linear association was present between age and clinical endpoints was evaluated using restricted cubic splines. We further explored the effects of intensive BP lowering across the age spectrum using interaction analyses. Results Age was noted for all individuals, and 3,805 (41%), 4,390 (47%), and 1,166 (12%) were <65 years, 65–79 years, and ≥80 years, respectively. Mean age was similar between the two study groups (intensive group 67.9 years vs. standard group 67.9 years; P=0.94). Median follow-up was 3.3 years (range 0–4.8), with 562 primary efficacy events (6%) and 3,529 primary safety events (38%) recorded during the study period. Age was linearly associated with the risk of stroke (test for overall trend, P<0.001) and non-linearly associated with the risk of primary efficacy events, death from CV causes, death from any cause, heart failure, and SAE (test for non-linearity, P<0.05; test for overall trend, P<0.001). Age remained significantly associated with all tested endpoints after multivariable adjustment (P<0.001). Furthermore, the risk of primary events increased over guideline-recommended age-categories (65–79 years vs. <65 years; adj. HR 1.65, 95% CI 1.34–2.04; P<0.001 and ≥80 years vs. 65–79 years; adj. HR 1.92, 95% CI 1.54–2.40; P<0.001), as did the risk of SAE (P<0.001). The safety and efficacy of intensive BP lowering was not modified by age whether tested continuously or categorically (P>0.05). The Figure shows similar treatment effects (hazard ratios) across the spectrum of age. P-values are for the interaction between age and treatment effect for each endpoint. Figure 1 Conclusions In SPRINT, higher age was associated with a greater risk of both CV events and SAE. However, intensive BP lowering appeared to be associated with similar risks and benefits across the age spectrum.

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First-Phase Ejection Fraction, a Measure of Preclinical Heart Failure, Is Strongly Associated With Increased Mortality in Patients With COVID-19

Hypertension ◽

10.1161/hypertensionaha.121.17099 ◽

2021 ◽

Author(s):

Haotian Gu ◽

Chiara Cirillo ◽

Adam A. Nabeebaccus ◽

Zhenxing Sun ◽

Lingyun Fang ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Proportional Hazards ◽

Clinical Laboratory ◽

Strong Predictor ◽

Cox Proportional Hazards ◽

Reactive Protein ◽

Proportional Hazards Regression ◽

Early Systole ◽

Union Hospital

Presence of heart failure is associated with a poor prognosis in patients with coronavirus disease 2019 (COVID-19). The aim of the present study was to examine whether first-phase ejection fraction (EF1), the ejection fraction measured in early systole up to the time of peak aortic velocity, a sensitive measure of preclinical heart failure, is associated with survival in patients hospitalized with COVID-19. A retrospective outcome study was performed in patients hospitalized with COVID-19 who underwent echocardiography (n=380) at the West Branch of the Union Hospital, Wuhan, China and in patients admitted to King’s Health Partners in South London, United Kingdom. Association of EF1 with survival was performed using Cox proportional hazards regression. EF1 was compared in patients with COVID-19 and in historical controls with similar comorbidities (n=266) who had undergone echocardiography before the COVID-19 pandemic. In patients with COVID-19, EF1 was a strong predictor of survival in each patient group (Wuhan and London). In the combined group, EF1 was a stronger predictor of survival than other clinical, laboratory, and echocardiographic characteristics including age, comorbidities, and biochemical markers. A cutoff value of 25% for EF1 gave a hazard ratio of 5.23 ([95% CI, 2.85–9.60]; P <0.001) unadjusted and 4.83 ([95% CI, 2.35–9.95], P <0.001) when adjusted for demographics, comorbidities, hs-cTnI (high-sensitive cardiac troponin), and CRP (C-reactive protein). EF1 was similar in patients with and without COVID-19 (23.2±7.3 versus 22.0±7.6%, P =0.092, adjusted for prevalence of risk factors and comorbidities). Impaired EF1 is strongly associated with mortality in COVID-19 and probably reflects preexisting, preclinical heart failure.

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Routinely reported ejection fraction and mortality in clinical practice: where does the nadir of risk lie?

European Heart Journal ◽

10.1093/eurheartj/ehz550 ◽

2019 ◽

Cited By ~ 9

Author(s):

Gregory J Wehner ◽

Linyuan Jing ◽

Christopher M Haggerty ◽

Jonathan D Suever ◽

Joseph B Leader ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Proportional Hazards ◽

Patient Characteristics ◽

Left Ventricular ◽

Cox Proportional Hazards ◽

Left Ventricular Ejection ◽

Validation Dataset ◽

Ventricular Ejection Fraction ◽

Hazard Ratios

Abstract Aims We investigated the relationship between clinically assessed left ventricular ejection fraction (LVEF) and survival in a large, heterogeneous clinical cohort. Methods and results Physician-reported LVEF on 403 977 echocardiograms from 203 135 patients were linked to all-cause mortality using electronic health records (1998–2018) from US regional healthcare system. Cox proportional hazards regression was used for analyses while adjusting for many patient characteristics including age, sex, and relevant comorbidities. A dataset including 45 531 echocardiograms and 35 976 patients from New Zealand was used to provide independent validation of analyses. During follow-up of the US cohort, 46 258 (23%) patients who had undergone 108 578 (27%) echocardiograms died. Overall, adjusted hazard ratios (HR) for mortality showed a u-shaped relationship for LVEF with a nadir of risk at an LVEF of 60–65%, a HR of 1.71 [95% confidence interval (CI) 1.64–1.77] when ≥70% and a HR of 1.73 (95% CI 1.66–1.80) at LVEF of 35–40%. Similar relationships with a nadir at 60–65% were observed in the validation dataset as well as for each age group and both sexes. The results were similar after further adjustments for conditions associated with an elevated LVEF, including mitral regurgitation, increased wall thickness, and anaemia and when restricted to patients reported to have heart failure at the time of the echocardiogram. Conclusion Deviation of LVEF from 60% to 65% is associated with poorer survival regardless of age, sex, or other relevant comorbidities such as heart failure. These results may herald the recognition of a new phenotype characterized by supra-normal LVEF.

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Erythrocyte n-6 Fatty Acids and Risk for Cardiovascular Outcomes and Total Mortality in the Framingham Heart Study

Nutrients ◽

10.3390/nu10122012 ◽

2018 ◽

Vol 10 (12) ◽

pp. 2012 ◽

Cited By ~ 8

Author(s):

William Harris ◽

Nathan Tintle ◽

Vasan Ramachandran

Keyword(s):

Fatty Acids ◽

Framingham Heart Study ◽

Proportional Hazards ◽

Clinical Status ◽

Total Mortality ◽

Cox Proportional Hazards ◽

Erythrocyte Membranes ◽

Cox Proportional Hazards Models ◽

Heart Study ◽

Full Profile

Background: The prognostic value of erythrocyte levels of n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined cardiovascular (CV) outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function of baseline levels of different length n-6 FAs (18 carbon, 20 carbon, and 22 carbon) in the erythrocyte membranes. Clinical outcomes were monitored for up to 9.5 years (median follow up, 7.26 years). Cox proportional hazards models were adjusted for a variety of demographic characteristics, clinical status, and red blood cell (RBC) n-6 and long chain n-3 FA content. Results: There were 245 CV events, 119 coronary heart disease (CHD) events, 105 ischemic strokes, 58 CVD deaths, and 350 deaths from all causes. Few associations between either mortality or CVD outcomes were observed for n-6 FAs, with those that were observed becoming non-significant after adjusting for n-3 FA levels. Conclusions: Higher circulating levels of marine n-3 FA levels are associated with reduced risk for incident CVD and ischemic stroke and for death from CHD and all-causes; however, in the same sample little evidence exists for association with n-6 FAs. Further work is needed to identify a full profile of FAs associated with cardiovascular risk and mortality.

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