cholesterol

Aim: The "2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia" retires and replaces the "2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol."

Methods: A comprehensive literature search was conducted from October 2024 to December 2024 to identify clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Structure: The focus of this clinical practice guideline is to address the evaluation, management, and monitoring of individuals with dyslipidemias, including high blood cholesterol, hypertriglyceridemia, and elevated lipoprotein(a).

Keywords: ACC/AHA clinical practice guideline; HDL; LDL; anticholesteremic agents; atherosclerosis; atherosclerotic disease; cardiovascular disease; cardiovascular diseases; cholesterol; drug interactions; dyslipidemia(s); hydroxymethylglutaryl-CoA reductase inhibitors; hypercholesterolemia; hyperlipid(a)emia/s; hyperlipoproteinemia type II; hypertriglyceridemia; hypolipidemic agents; lipids; lipoprotein(a); primary prevention; risk adjustment; risk assessment; risk factors; simvastatin; statin(s); triglycerides.

Author/s:

Roger S. Blumenthal, Pamela B. Morris, Mario Gaudino, Heather M. Johnson, Timothy S. Anderson, Vera A. Bittner, Ron Blankstein, LaPrincess C. Brewer, Leslie Cho, Sarah D. de Ferranti, Eugenia Gianos, Ty J. Gluckman, Kristen F. Gradney, Ijeoma Isiadinso, Donald M. Lloyd-Jones, Joel C. Marrs, Seth S. Martin, Kellie H. McLain, Laxmi S. Mehta, Samia Mora, Wudeneh M. Mulugeta, Pradeep Natarajan, Ann Marie Navar, Carl E. Orringer, Tamar S. Polonsky, Harmony R. Reynolds, Joseph J. Saseen, Michael D. Shapiro, Daniel E. Soffer, Sheila A. Tynes, Chloé D. Villavaso, Salim S. Virani, John T. Wilkins

Managing Hypercholesterolemia in Adults Older Than 75 years Without a History of Atherosclerotic Cardiovascular Disease: An Expert Clinical Consensus From the National Lipid Association and the American Geriatrics Society

Alex Haga — Mon, 14 Apr 2025 18:17:35 +0000

Date Added:

April 14, 2025

Journal/Publication:

Journal of the American Geriatrics Society

Publication Date:

April 10, 2025

URL:

Managing Hypercholesterolemia in Adults Older Than 75 years Without a History of Atherosclerotic Cardiovascular Disease: An Expert Clinical Consensus From the National Lipid Association and the American Geriatrics Society

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1111/jgs.19398

Keywords

hypercholesterolemia

older adult

primary prevention

PMID (1):

40207842

MeSH

cardiovascular diseases

cholesterol

primary prevention

A summary of the evidence and recommendations regarding treatment of people over 75 with statins. James W. Mold, MD, MPH

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The risk of atherosclerotic cardiovascular disease increases with advancing age. Elevated LDL-cholesterol and non-HDL-cholesterol levels remain predictive of incident atherosclerotic cardiovascular events among individuals older than 75 years. Risk prediction among older individuals is less certain because most current risk calculators lack specificity in those older than 75 years and do not adjust for co-morbidities, functional status, frailty, and cognition which significantly impact prognosis in this age group. Data on the benefits and risks of lowering LDL-cholesterol with statins in older patients without atherosclerotic cardiovascular disease are also limited since most primary prevention trials have included mostly younger patients. Available data suggest that statin therapy in older primary prevention patients may reduce atherosclerotic cardiovascular events and that benefits from lipid-lowering with statins outweigh potential risks such as statin-associated muscle symptoms and incident Type 2 diabetes mellitus. While some evidence suggests the possibility that statins may be associated with incident cognitive impairment in older adults, a preponderance of literature indicates neutral or even protective statin-related cognitive effects. Shared decision-making which is recommended for all patients when considering statin therapy is particularly important in older patients. Randomized clinical trial data evaluating the use of non-statin lipid-lowering therapy in older patients are sparse. Deprescribing of lipid-lowering agents may be appropriate for select patients older than 75 years with life-limiting diseases. Finally, a patient-centered approach should be taken when considering primary prevention strategies for older adults.

Author/s:

Vera Bittner, Sunny A Linnebur, Dave L Dixon, Daniel E Forman, Ariel R Green

Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study

Linda Fowler — Wed, 10 Jan 2024 14:41:05 +0000

Date Added:

January 10, 2024

Journal/Publication:

Alzheimer's Research & Therapy

Publisher:

BMC

Publication Date:

December 20, 2023

Issue:

220

Volume:

URL:

Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1186/s13195-023-01360-0

Keywords

alzheimer's disease

Cholesterol metabolism

Cognitive impairment

cohort study

HMG-CoA reductase inhibitors

statins

PMID (1):

38115091

MeSH

Alzheimer Disease* / drug therapy

Atorvastatin / therapeutic use

Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use

Simvastatin / therapeutic use

cholesterol

cohort studies

Alzheimer Disease* / epidemiology

Humans

This cohort study of patients with dementia appears to show that statins seem to reduce the rate of progression of cognitive decline. That is certainly reassuring for those of us who have been concerned about whether we are depriving our brain cells of the cholesterol they require. James W. Mold, MD, MPH

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Background
Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer’s disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms.

Objective
To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment.

Methods
A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users.

Results
Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent.

Conclusions
Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses

Author/s:

Bojana Petek, Henrike Häbel, Hong Xu, Marta Villa-Lopez, Irena Kalar, Minh Tuan Hoang, Silvia Maioli, Joana B Pereira, Shayan Mostafaei, Bengt Winblad, Milica Gregoric Kramberger, Maria Eriksdotter, Sara Garcia-Ptacek

Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment A Systematic Review and Meta-analysis

Saige Blanchard — Tue, 10 May 2022 05:00:00 +0000

Date Added:

May 10, 2022

Journal/Publication:

JAMA Internal Medicine

Publisher:

American Medical Association

Publication Date:

March 14, 2022

Issue:

Volume:

182

Pages:

474-481

URL:

Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment A Systematic Review and Meta-analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamainternmed.2022.0134

Keywords

PMID (1):

35285850

MeSH

Hydroxymethylglutaryl-CoA Reductase Inhibitors

cholesterol

LDL

Numbers Needed to Treat

risk

Cl 22

Consensus

As for many of our most common interventions, the actual impact of statins on cardiovascular event rates and mortality are small unless the pre-intervention risk of such events is quite high or unless the intervention is reliably continued for long periods of time. As we knew, the effect of statins is not entirely related to LDL cholesterol reduction. James W. Mold, MD, MPH

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Importance: The association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than composite, outcomes, such as all-cause mortality, myocardial infarction, or stroke, is unclear.

Objective: To assess the association between absolute reductions in LDL-C levels with treatment with statin therapy and all-cause mortality, myocardial infarction, and stroke to facilitate shared decision-making between clinicians and patients and inform clinical guidelines and policy.

Data sources: PubMed and Embase were searched to identify eligible trials from January 1987 to June 2021.

Study selection: Large randomized clinical trials that examined the effectiveness of statins in reducing total mortality and cardiovascular outcomes with a planned duration of 2 or more years and that reported absolute changes in LDL-C levels. Interventions were treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) vs placebo or usual care. Participants were men and women older than 18 years.

Data extraction and synthesis: Three independent reviewers extracted data and/or assessed the methodological quality and certainty of the evidence using the risk of bias 2 tool and Grading of Recommendations, Assessment, Development and Evaluation. Any differences in opinion were resolved by consensus. Meta-analyses and a meta-regression were undertaken.

Main outcomes and measures: Primary outcome: all-cause mortality. Secondary outcomes: myocardial infarction, stroke.

Findings: Twenty-one trials were included in the analysis. Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins, with associated relative risk reductions of 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%) respectively. A meta-regression exploring the potential mediating association of the magnitude of statin-induced LDL-C reduction with outcomes was inconclusive.

Conclusions and relevance: The results of this meta-analysis suggest that the absolute risk reductions of treatment with statins in terms of all-cause mortality, myocardial infarction, and stroke are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence. A conclusive association between absolute reductions in LDL-C levels and individual clinical outcomes was not established, and these findings underscore the importance of discussing absolute risk reductions when making informed clinical decisions with individual patients.

Author/s:

Byrne, P., Demasi, M., Jones, M., Smith, S. M., O'Brien, K. K., DuBroff, R.

Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial

Brian Desmarais — Thu, 24 Oct 2019 17:04:27 +0000

Date Added:

April 3, 2020

Journal/Publication:

European Heart Journal

Publication Date:

October 22, 2019

URL:

Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1093/eurheartj/ehz754

Keywords

Perhaps once a day antihypertensives should be taken at night rather than in the AM. James W. Mold, MD, MPH

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AIMS:

The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.

METHODS AND RESULTS:

In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome [0.55 (95% CI 0.50-0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34-0.56)], myocardial infarction [0.66 (0.52-0.84)], coronary revascularization [0.60 (0.47-0.75)], heart failure [0.58 (0.49-0.70)], and stroke [0.51 (0.41-0.63)].

CONCLUSION:

Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.

TRIAL REGISTRATION:

ClinicalTrials.gov, number NCT00741585.

Author/s:

Hermida, R.C., Crespo, J.J., Domínguez-Sardiña, M, Otero, A., Moyá, A., Ríos, M.T., Sineiro, E., Castiñeira, M.C., Callejas, P.A., Pousa, L., Salgado, J.L., Durán, C., Sánchez, J.J., Fernández, J.R., Mojón, A., Ayala, D.E., Hygia Project Investigators

Diagnosis of osteoporosis in statin-treated patients is dose-dependent

Brian Desmarais — Thu, 17 Oct 2019 14:44:10 +0000

Date Added:

October 17, 2019

Journal/Publication:

Annals of Rheumatic Diseases

Publication Date:

September 16, 2019

URL:

Diagnosis of osteoporosis in statin-treated patients is dose-dependent

Type:

Clinical Research Results

DOI (1):

10.1136/annrheumdis-2019-215714.

Keywords

MeSH

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Gonadal Steroid Hormones

Computers

Hydroxymethylglutaryl CoA Reductases

osteoporosis

It was bound to happen now that most statins are generic, the adverse effects are going to be revealed. Apparently high-dose statins increase the likelihood of a subsequent osteoporosis diagnosis. Even though this is a cohort study, not an RCT, the dose response relationship makes the results more credible. James W. Mold, MD, MPH

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OBJECTIVE:

Whether HMG-CoA-reductase inhibition, the main mechanism of statins, plays a role in the pathogenesis of osteoporosis, is not entirely known so far. Consequently, this study was set out to investigate the relationship of different kinds and dosages of statins with osteoporosis, hypothesising that the inhibition of the synthesis of cholesterol could influence sex-hormones and therefore the diagnosis of osteoporosis.

METHODS:

Medical claims data of all Austrians from 2006 to 2007 was used to identify all patients treated with statins to compute their daily defined dose averages of six different types of statins. We applied multiple logistic regression to analyse the dose-dependent risks of being diagnosed with osteoporosis for each statin individually.

RESULTS:

In the general study population, statin treatment was associated with an overrepresentation of diagnosed osteoporosis compared with controls (OR: 3.62, 95% CI 3.55 to 3.69, p<0.01). There was a highly non-trivial dependence of statin dosage with the ORs of osteoporosis. Osteoporosis was underrepresented in low-dose statin treatment (0-10 mg per day), including lovastatin (OR: 0.39, CI 0.18 to 0.84, p<0.05), pravastatin (OR: 0.68, 95% CI 0.52 to 0.89, p<0.01), simvastatin (OR: 0.70, 95% CI 0.56 to 0.86, p<0.01) and rosuvastatin (OR: 0.69, 95% CI 0.55 to 0.87, p<0.01). However, the exceeding of the 40 mg threshold for simvastatin (OR: 1.64, 95% CI 1.31 to 2.07, p<0.01), and the exceeding of a 20 mg threshold for atorvastatin (OR: 1.78, 95% CI 1.41 to 2.23, p<0.01) and for rosuvastatin (OR: 2.04, 95% CI 1.31 to 3.18, p<0.01) was related to an overrepresentation of osteoporosis.

CONCLUSION:

Our results show that the diagnosis of osteoporosis in statin-treated patients is dose-dependent. Thus, osteoporosis is underrepresented in low-dose and overrepresented in high-dose statin treatment, demonstrating the importance of future studies' taking dose-dependency into account when investigating the relationship between statins and osteoporosis.

Author/s:

Leutner, M., Matzhold, C., Bellach, L., Deischinger, C., Harreiter, J., Thurner, S., Klimek, P., Kautzky-Willer, A.

Psyllium fiber improves glycemic control proportional to loss of glycemic control: a meta-analysis of data in euglycemic subjects, patients at risk of type 2 diabetes mellitus, and patients being treated for type 2 diabetes mellitus

Tracy Ashby — Tue, 09 Apr 2019 05:00:00 +0000

Date Added:

April 9, 2019

Journal/Publication:

The American Journal of Clinical Nutrition

Publisher:

American Society for Nutrition

Publication Date:

November 11, 2015

Issue:

Volume:

102

Pages:

1604-1614

URL:

Psyllium fiber improves glycemic control proportional to loss of glycemic control: a meta-analysis of data in euglycemic subjects, patients at risk of type 2 diabetes mellitus, and patients being treated for type 2 diabetes mellitus

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.3945/ajcn.115.106989

Keywords

PMID (1):

26561625

MeSH

diabetes mellitus, type 2

glycated hemoglobin a

cholesterol

This 2015 meta-analysis found that the addition of 5 – 10 gm of psyllium husks taken before each meal reduced A1cs in type 2 diabetics by an average of 1%, comparable to most diabetes meds. Most patients will have to work their way up to that dose gradually I suspect. James W. Mold, MD, MPH

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BACKGROUND:

A number of health benefits are associated with intake of soluble, viscous, gel-forming fibers, including reduced serum cholesterol and the attenuation of postprandial glucose excursions.

OBJECTIVE:

We assess the effects of psyllium, which is a soluble, gel-forming, nonfermented fibersupplement, on glycemic control in patients who were being treated for type 2 diabetes mellitus (T2DM) and in patients who were at risk of developing T2DM.

DESIGN:

A comprehensive search was performed of available published literature (Scopus scientific database) and clinical records stored by Procter & Gamble with the use of key search terms to identify clinical studies that assessed the glycemic effects of psyllium in nondiabetic, pre-T2DM, and T2DM patients.

RESULTS:

We identified 35 randomized, controlled, clinical studies that spanned 3 decades and 3 continents. These data were assessed in 8 meta-analyses. In patients with T2DM, multiweek studies (psyllium dosed before meals) showed significant improvement in both the fasting blood glucose (FBG) concentration (-37.0 mg/dL; P < 0.001) and glycated hemoglobin (HbA1c) [-0.97% (-10.6 mmol/mol); P = 0.048]. Glycemic effects were proportional to baseline FBG; no significant glucose lowering was observed in euglycemic subjects, a modest improvement was observed in subjects with pre-T2DM, and the greatest improvement was observed in subjects who were being treated for T2DM.

CONCLUSIONS:

These data indicate that psyllium would be an effective addition to a lifestyle-intervention program. The degree of psyllium's glycemic benefit was commensurate with the loss of glycemic control. Because the greatest effect was seen in patients who were being treated for T2DM, additional studies are needed to determine how best to incorporate psyllium into existing prevention and treatment algorithms with concomitant hypoglycemic medications.

Author/s:

Gibb, Roger D., McRorie, Johnson W., Russell, Darrell A., Hasselblad, Vic, D'Alessio, David A.

Management of Blood Cholesterol

Jeffrey Wilson — Tue, 05 Feb 2019 20:01:21 +0000

Date Added:

February 5, 2019

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

February 4, 2019

URL:

Management of Blood Cholesterol

DOI (1):

doi:10.1001/jama.2019.0015

Keywords

MeSH

myocardial infarction

cholesterol

This is an update to the 2013 blood cholesterol guidelines developed by the AHA, ACC and others. It re-adds LDL targets and the addition of cholesterol-lowering agents other than statins when necessary.

Pharmacologically lowering low-density lipoprotein cholesterol (LDL-C) consistently reduces ASCVD events (myocardial infarction, stroke, and cardiovascular death), and the principle that lower LDL-C is better was reaffirmed by trials that added ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to statin therapy. The 2013 guideline removed specific LDL-C treatment targets, but high-quality trials since offered the opportunity to reintroduce such goals based on risk gradations.

Author/s:

Alenghat, Francis J., Davis, Andrew M.

The Mediterranean Diet: What You Need to Know About Eating the Mediterranean Way

Tracy Ashby — Fri, 02 Nov 2018 05:00:00 +0000

Date Added:

November 2, 2018

Publisher:

HelpGuide.org

Publication Date:

September 1, 2018

URL:

The Mediterranean Diet: What You Need to Know About Eating the Mediterranean Way

Type:

Patient Education Materials

Format:

Article

Keywords

MeSH

This is an explanation of the Mediterranean Diet.

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When you think about Mediterranean food, your mind may go to pizza and pasta from Italy, or lamb chops from Greece, but these dishes don’t fit into the healthy dietary plans advertised as “Mediterranean.” A true Mediterranean diet consists mainly of fruits and vegetables, seafood, olive oil, hearty grains, and other foods that help fight against heart disease, certain cancers, diabetes, and cognitive decline. It’s a diet worth chasing; making the switch from pepperoni and pasta to fish and avocados may take some effort, but you could soon be on a path to a healthier and longer life.

Author/s:

Smith, Melinda, Segal, Robert

Cholesterol Management in Primary Care

Jeffrey Wilson — Wed, 05 Sep 2018 15:42:28 +0000

Date Added:

September 5, 2018

Journal/Publication:

Healthy Hearts for Oklahoma

Publisher:

Agency for Healthcare Research and Quality

Type:

Clinical Decision Aids

Format:

Slides

Keywords

MeSH

Hydroxymethylglutaryl-CoA Reductase Inhibitors

cholesterol

primary prevention

This is the decision aid for statin use developed for the Healthy Hearts for OK Project.

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Patients with existing disease or major risk factors should be prescribed statins unless contraindicated.

Omega-6 fats for the primary and secondary prevention of cardiovascular disease

Tracy Ashby — Fri, 24 Aug 2018 05:00:00 +0000

Date Added:

August 25, 2018

Journal/Publication:

The Cochrane Database of Systematic Reviews

Publisher:

John Wiley & Sons, Ltd

Publication Date:

July 18, 2018

Issue:

Volume:

Pages:

CD011094

URL:

Omega-6 fats for the primary and secondary prevention of cardiovascular disease

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1002/14651858.CD011094.pub3

Keywords

omega-6 fatty acids

cardiovascular disease

PMID (1):

30019765

MeSH

This large meta-analysis suggests that supplementation with omega 6 fatty acids does not significantly improve meaningful outcomes.

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BACKGROUND:

Omega-6 fats are polyunsaturated fats vital for many physiological functions, but their effect on cardiovascular disease (CVD) risk is debated.

OBJECTIVES:

To assess effects of increasing omega-6 fats (linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA)) on CVD and all-cause mortality.

SEARCH METHODS:

We searched CENTRAL, MEDLINE and Embase to May 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews.

SELECTION CRITERIA:

We included randomised controlled trials (RCTs) comparing higher versus lower omega-6 fat intake in adults with or without CVD, assessing effects over at least 12 months. We included full texts, abstracts, trials registry entries and unpublished studies. Outcomes were all-cause mortality, CVD mortality, CVD events, risk factors (blood lipids, adiposity, blood pressure), and potential adverse events. We excluded trials where we could not separate omega-6 fat effects from those of other dietary, lifestyle or medication interventions.

DATA COLLECTION AND ANALYSIS:

Two authors independently screened titles/abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias of included trials. We wrote to authors of included studies. Meta-analyses used random-effects analysis, while sensitivity analyses used fixed-effects and limited analyses to trials at low summary risk of bias. We assessed GRADE quality of evidence for 'Summary of findings' tables.

MAIN RESULTS:

We included 19 RCTs in 6461 participants who were followed for one to eight years. Seven trials assessed the effects of supplemental GLA and 12 of LA, none DGLA or AA; the omega-6 fats usually displaced dietary saturated or monounsaturated fats. We assessed three RCTs as being at low summary risk of bias.Primary outcomes: we found low-quality evidence that increased intake of omega-6 fats may make little or no difference to all-cause mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.12, 740 deaths, 4506 randomised, 10 trials) or CVD events (RR 0.97, 95% CI 0.81 to 1.15, 1404 people experienced events of 4962 randomised, 7 trials). We are uncertain whether increasing omega-6 fats affects CVD mortality (RR 1.09, 95% CI 0.76 to 1.55, 472 deaths, 4019 randomised, 7 trials), coronary heart disease events (RR 0.88, 95% CI 0.66 to 1.17, 1059 people with events of 3997 randomised, 7 trials), major adverse cardiac and cerebrovascular events (RR 0.84, 95% CI 0.59 to 1.20, 817 events, 2879 participants, 2 trials) or stroke (RR 1.36, 95% CI 0.45 to 4.11, 54 events, 3730 participants, 4 trials), as we assessed the evidence as being of very low quality. We found no evidence of dose-response or duration effects for any primary outcome, but there was a suggestion of greater protection in participants with lower baseline omega-6 intake across outcomes.Additional key outcomes: we found increased intake of omega-6 fats may reduce myocardial infarction (MI) risk (RR 0.88, 95% CI 0.76 to 1.02, 609 events, 4606 participants, 7 trials, low-quality evidence). High-quality evidence suggests increasing omega-6 fats reduces total serum cholesterol a little in the long term (mean difference (MD) -0.33 mmol/L, 95% CI -0.50 to -0.16, I2 = 81%; heterogeneity partially explained by dose, 4280 participants, 10 trials). Increasing omega-6 fats probably has little or no effect on adiposity (body mass index (BMI) MD -0.20 kg/m2, 95% CI -0.56 to 0.16, 371 participants, 1 trial, moderate-quality evidence). It may make little or no difference to serum triglycerides (MD -0.01 mmol/L, 95% CI -0.23 to 0.21, 834 participants, 5 trials), HDL (MD -0.01 mmol/L, 95% CI -0.03 to 0.02, 1995 participants, 4 trials) or low-density lipoprotein (MD -0.04 mmol/L, 95% CI -0.21 to 0.14, 244 participants, 2 trials, low-quality evidence).

AUTHORS' CONCLUSIONS:

This is the most extensive systematic assessment of effects of omega-6 fats on cardiovascular health, mortality, lipids and adiposity to date, using previously unpublished data. We found no evidence that increasing omega-6 fats reduces cardiovascular outcomes other than MI, where 53 people may need to increase omega-6 fat intake to prevent 1 person from experiencing MI. Although benefits of omega-6 fats remain to be proven, increasing omega-6 fats may be of benefit in people at high risk of MI. Increased omega-6 fats reduce serum total cholesterol but not other blood fat fractions or adiposity.

Author/s:

Hooper, Lee, Al-Khudairy, Lena, Abdelhamid, Asmaa S., Rees, Karen, Brainard, Julii S., Brown, Tracey J., Ajabnoor, Sarah M., O'Brien, Alex T., Winstanley, Lauren E., Donaldson, Daisy H., Song, Fujian, Deane, Katherine H. O.

Omega-3 Fatty Acids and Cardiovascular Disease: Current State of the Evidence

Tracy Ashby — Mon, 20 Aug 2018 05:00:00 +0000

Date Added:

August 21, 2018

Journal/Publication:

Effective Health Care Program

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

July 25, 2017

Issue:

URL:

Omega-3 Fatty Acids and Cardiovascular Disease: Current State of the Evidence

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

Keywords

MeSH

Marine oil supplements high in omega 3 fatty acids significantly lower triglycerides and increase HDL and LDL a little, but they don’t reduce the risk of cardiovascular events.

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Focus of This Summary

This is a summary of a systematic review that evaluated the recent evidence regarding the effects of omega-3 fatty acids (FAs), primarily from marine oil supplements, on clinical and selected intermediate cardiovascular (CV) outcomes (i.e., blood pressure, lipid concentrations) and the association of omega-3 FA dietary intake and biomarkers with CV outcomes. The systematic review included 147 articles published between 2000 and June 2015. Studies that analyzed levels of fish (or other food) consumption without exact quantification of omega-3 FA intake were excluded from this review. This summary is provided to assist in informed clinical decisionmaking. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.

Background

The first observation of a link between fish consumption and cardiovascular (CV) health was made in the late 1970s in a Greenland Eskimo population. This population exhibited a comparatively low rate of CV mortality and consumed a greater than average amount of fish. Since this original observation, there have been hundreds of studies conducted to evaluate the effect of omega-3 fatty acids (FAs) on cardiovascular disease (CVD), its risk factors, and its biomarkers.

The omega-3 FAs include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and alpha-linolenic acid (ALA). These are essential long-chain and very-long-chain polyunsaturated fatty acids that have many physiological effects, including inflammation regulation. EPA, DHA, and DPA are found in fish and other seafood (called dietary marine oils), as well as in supplements prepared from these foods (referred to here as marine oil supplements). ALA is found in walnuts, leafy green vegetables, and oils such as canola, soy, and flaxseed.

An original systematic review of omega-3 FAs was prepared by the Agency for Healthcare and Research Quality in 2004.1,2 Based on the observational studies available at that time, several expert panels suggested that regular consumption of fish and seafood is associated with lower risk of coronary heart disease (CHD) and cardiac death. The recommendations were based on assumptions of benefits from EPA and DHA and their content in fish and seafood.

The current systematic review aimed to update the evidence in light of the more recent literature published on the topic and included both randomized controlled trials (RCTs) and observational studies. Studies that analyzed levels of fish (or other food) consumption without exact quantification of omega-3 FA intake were excluded.

Conclusions

Observational studies suggest possible benefits of dietary intake of marine oils (such as through consumption of fish) for CV death and total stroke (mainly ischemic stroke).

In contrast, there is high strength of evidence (SOE) from RCTs that marine oil supplements do not affect the risk of major adverse cardiac events (MACE), all-cause death, sudden cardiac death, revascularization, or high blood pressure (BP). Marine oil supplements also have no effect on the risk of atrial fibrillation (moderate SOE). Importantly, RCTs focused primarily on marine oil supplements, not on food sources.

Marine oil supplements affect several intermediate outcomes. First, they significantly lower triglycerides (TGs)—possibly having greater effects in higher doses and in people with higher baseline TGs. Second, they cause small increases in both high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c). Finally, marine oil supplements produce small changes in the ratio of total cholesterol to HDL-c (high SOE).

Author/s:

Balk, Ethan M., Adam, Gaelen P., Langberg, Valerie, Halladay, Christopher, Chung, Mei, Lin, Lin, Robertson, Sarah, Yip, Agustin, Steele, Dale, Smith, Bryant T., Lau, Joseph, Lichtenstein, Alice H., Trikalinos, Thomas A.

Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials

Tracy Ashby — Sun, 18 Feb 2018 06:00:00 +0000

Date Added:

February 18, 2019

Journal/Publication:

The Lancet

Publisher:

Elsevier Inc.

Publication Date:

February 2, 2019

Issue:

10170

Volume:

393

Pages:

407-415

URL:

Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/S0140-6736(18)31942-1

Keywords

statin

statin therapy

cholesterol, LDL

PMID (1):

30712900

MeSH

Hydroxymethylglutaryl-CoA Reductase Inhibitors

cholesterol

cholesterol, LDL

risk reduction behavior

Statins appear to work just as well in patients over the age of 75 as they do in younger patients.

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BACKGROUND:

Statin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safetyamong older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages.

METHODS:

In this meta-analysis, randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years. We analysed individual participant data from 22 trials (n=134 537) and detailed summary data from one trial (n=12 705) of statin therapy versus control, plus individual participant data from five trials of more intensive versus less intensive statin therapy (n=39 612). We subdivided participants into six age groups (55 years or younger, 56-60 years, 61-65 years, 66-70 years, 71-75 years, and older than 75 years). We estimated effects on major vascular events (ie, major coronary events, strokes, and coronary revascularisations), cause-specific mortality, and cancer incidence as the rate ratio (RR) per 1·0 mmol/L reduction in LDL cholesterol. We compared proportional risk reductions in different age subgroups by use of standard χ2 tests for heterogeneity when there were two groups, or trend when there were more than two groups.

FINDINGS:

14 483 (8%) of 186 854 participants in the 28 trials were older than 75 years at randomisation, and the median follow-up duration was 4·9 years. Overall, statin therapy or a more intensive statin regimen produced a 21% (RR 0·79, 95% CI 0·77-0·81) proportional reduction in major vascular events per 1·0 mmol/L reduction in LDL cholesterol. We observed a significant reduction in major vascular events in all age groups. Although proportional reductions in major vascular events diminished slightly with age, this trend was not statistically significant (ptrend=0·06). Overall, statin or more intensive therapy yielded a 24% (RR 0·76, 95% CI 0·73-0·79) proportional reduction in major coronary events per 1·0 mmol/L reduction in LDL cholesterol, and with increasing age, we observed a trend towards smaller proportional risk reductions in major coronary events (ptrend=0·009). We observed a 25% (RR 0·75, 95% CI 0·73-0·78) proportional reduction in the risk of coronary revascularisation procedures with statin therapy or a more intensive statin regimen per 1·0 mmol/L lower LDL cholesterol, which did not differ significantly across age groups (ptrend=0·6). Similarly, the proportional reductions in stroke of any type (RR 0·84, 95% CI 0·80-0·89) did not differ significantly across age groups (ptrend=0·7). After exclusion of four trials which enrolled only patients with heart failure or undergoing renal dialysis (among whom statin therapy has not been shown to be effective), the trend to smaller proportional risk reductions with increasing age persisted for major coronary events (ptrend=0·01), and remained non-significant for major vascular events (ptrend=0·3). The proportional reduction in major vascular events was similar, irrespective of age, among patients with pre-existing vascular disease (ptrend=0·2), but appeared smaller among older than among younger individuals not known to have vascular disease (ptrend=0·05). We found a 12% (RR 0·88, 95% CI 0·85-0·91) proportional reduction in vascular mortality per 1·0 mmol/L reduction in LDL cholesterol, with a trend towards smaller proportional reductions with older age (ptrend=0·004), but this trend did not persist after exclusion of the heart failure or dialysis trials (ptrend=0·2). Statin therapy had no effect at any age on non-vascular mortality, cancer death, or cancer incidence.

INTERPRETATION:

Statin therapy produces significant reductions in major vascular events irrespective of age, but there is less direct evidence of benefit among patients older than 75 years who do not already have evidence of occlusive vascular disease. This limitation is now being addressed by further trials.

FUNDING:

Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation.

Author/s:

Cholesterol Treatment Trialists' Collaboration