Journal of the American Geriatrics Society Journal of the
American Geriatrics Society
SPECIAL ARTICLE OPEN ACCESS
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
Vera Bittner1 | Sunny A. Linnebur2 | Dave L. Dixon3 | Daniel E. Forman4 | Ariel R. Green5 | Terry A. Jacobson6 |
Ariela R. Orkaby 7 | Joseph J. Saseen8 | Salim S. Virani9,10
1Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama, USA | 2University of Colorado Skaggs School of
Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA | 3Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth
University School of Pharmacy, Richmond, Virginia, USA | 4Department of Medicine (Divisions of Geriatrics and Cardiology), University of Pittsburgh and
Pittsburgh Geriatrics, Research, Education, and Clinical Center (GRECC), VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA | 5Division
of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA | 6Lipid Clinic and Cardiovascular
Risk Reduction Program, Department of Medicine, Emory University, Atlanta, Georgia, USA | 7 New England Geriatric Education, Research and Clinical
Center (GRECC), VA Boston Health Care System, Division of Aging, Brigham & Women's Hospital, Harvard Medical School, USA | 8Department of
Clinical Pharmacy and Department of Family Medicine, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA | 9Section of Cardiology,
Department of Medicine, The Aga Khan University, Karachi, Pakistan | 10 Texas Heart Institute and Baylor College of Medicine, Houston, Texas, USA
Correspondence: Vera Bittner
Received: 15 August 2024 | Accepted: 7 September 2024
Keywords: hypercholesterolemia | primary prevention | older adult
ABSTRACT
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 cardio-
vascular disease are also limited since most primary prevention trials have included mostly younger patients. Available data sug-
gest 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.
Abbreviations: AGS, American Geriatrics Society; ASCVD, Atherosclerotic cardiovascular disease; CAC, Coronary artery calcium; CI, confidence interval; T2DM, Type 2 Diabetes mellitus;
HR, Hazard ratio; LDL or LDL-C , Low density lipoprotein (− cholesterol); MI, myocardial infarction; NLA, National Lipid Association; NNT, Number needed to treat; non-H DL-C , non-H DL-
cholesterol; OR, Odds ratio; PCE, Pooled cohort equations; SAMS, Statin associated muscle symptoms; U.S., United States.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is
properly cited.
© 2025 The Author(s). Published by Elsevier Inc on behalf of National Lipid Association and John Wiley and Sons Inc. on behalf of American Geriatrics Society. This paper was jointly developed
by Journal of Clinical Lipidology and Journal of the American Geriatrics Society. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style.
Either citation can be used when citing this article.
Journal of the American Geriatrics Society, 2025; 0:1–23 1 of 23
https://doi.org/10.1111/jgs.19398
, 15325415, 0, Downloaded from https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.19398 by EBMG ACCESS - ETHIOPIA, Wiley Online Library on [11/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Preamble Synopsis
Since 2014, the National Lipid Association (NLA) has issued Cross-sectional and prospective cohort studies show that ath-
several scientific statements on key aspects of the manage- erogenic lipoproteins increase with age from early adulthood to
ment of lipids and lipoproteins to prevent cardiovascular the 7th decade, but gradually decrease in subsequent decades.3, 4
disease (https://w ww.l ipid.org/practicetools/documents). This decrease among the oldest old (8th decade and beyond) is
The current Expert Clinical Consensus, focused on the treat- likely multifactorial including survivor bias (i.e., selective mor-
ment of hypercholesterolemia among individuals older than tality at younger ages among those with the highest atherogenic
75 years without clinically manifest atherosclerotic cardio lipoprotein levels) and declines in cholesterol associated with
vascular disease (ASCVD), was developed as a collaboration co-morbidities (e.g., heart failure, malignancies, malnutrition).
between the NLA and the American Geriatrics Society (AGS). Many studies have shown strong and graded associations be-
The governing bodies of both organizations appointed mem- tween LDL-C level and incident ASCVD in women and men and
bers with relevant expertise to the writing group which was across ethnicities among young and middle-aged populations.
jointly chaired by a representative of NLA (V. B.) and AGS In contrast, early epidemiologic analyses among older individ-
(S.A.L.). The Expert Clinical Consensus was developed by a uals suggested an inverse association between total cholesterol
diverse group of clinical lipidologists, cardiologists, geriatri- and outcomes which is most consistent with reverse causation.5
cians, and pharmacists with cumulative expertise in clinical More contemporary analyses suggest that the association of
medicine, geriatrics, cardiology, endocrinology, pharmacol- LDL-C level to incident ASCVD is maintained in the oldest age
ogy, clinical trials, epidemiology, health outcomes research, groups.6
and public health.
Recommendation-specific supportive text
The chairs and members of the writing group jointly devel-
oped a set of key clinical questions to be addressed by the In 2007, a meta-analysis of 61 prospective studies analyzed isch-
panel. Once the key clinical questions were agreed upon, writ- emic heart disease mortality as a function of total cholesterol or
ing assignments were jointly determined by the group based non-high-density lipoprotein cholesterol (non- HDL- C) strati-
on content expertise with a primary and secondary author fied by sex and age (5th to 9th decade).7 Relative risk of ischemic
assigned to each question. The literature was reviewed and heart disease mortality related to the level of total cholesterol or
recommendations were developed using the 2019 Update of non-HDL-C was highest among 40-49 year-olds. Relative risk de-
the American Heart Association (AHA) / American College creased in a graded fashion with each advancing decade, but it
of Cardiology (ACC) rating system for clinical guidelines, remained statistically significant to age 80-89 years. In contrast,
assigning a Class of Recommendation (I-III) and a Level of absolute risk was lowest in the youngest age group and increased
Evidence (A-C with sub categories) for each recommenda- with advancing age.
tion (Figure 1).1, 2 Each section and its associated recom-
mendations were discussed in detail by the writing group. The prospective Copenhagen General Study investigated the
Preliminary recommendations were presented at the Annual association of LDL- C with incident myocardial infarction
Scientific Meeting of AGS (AGS23) in May 2023 and feedback (MI) and ASCVD in 91,131 participants ranging in age from
from the audience was incorporated as appropriate. Final 20-100 years old; 10,591 participants were 70-79 years old and
recommendations based on consensus of at least 60% of the 3,188 participants were 80-100 years old.6 Higher LDL-C was
expert panel were then reviewed by external peer reviewers, predictive of incident MI and ASCVD independent of age. As in
edited as appropriate and approved by the respective Boards of the Prospective Studies Collaboration, relative risks of MI and
the NLA and AGS on 9/20/2024. ASCVD (expressed as adjusted hazard ratios (HRadj)) were
highest in the youngest (20-49 year-old) age group (MI HRadj
1.68 (95% CI 1.45-1.87); ASCVD HRadj 1.47 (95% CI 1.32-1.64))
and lowest in the oldest (80-100 year-old) age group (MI HRadj
1.28 (95% CI 1.08-1.52); ASCVD HRadj 1.16 (95% CI 1.05-1.29)).
By contrast, absolute risk of events was lowest in the youngest
QUESTION 1 | For the population of adults older than 75 years age group and highest in the oldest age group. Based on these
without established ASCVD, what is the association between prospective observational data, the authors estimated the num-
low-density lipoprotein cholesterol (LDL-C) and incident ASCVD? ber needed to treat (NNT) to prevent MI or ASCVD for every
1 mmol/L (38.67 mg/dL) lowering of LDL-C over 5 years. The
estimated NNT declined with each decade of age (Figure 2).
For ASCVD, the estimated NNT for 80-100 year-old partici-
pants was 42 compared to 345 for 50-59 year-old participants;
for MI, the respective estimated NNTs were 80 and 439. Thus,
LDL-C is an important risk factor among patients older than
75 years and should be measured for ASCVD risk stratification.
2 of 23 Journal of the American Geriatrics Society, 2025
,15325415, 0, Downloaded from https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.19398 by EBMG ACCESS - ETHIOPIA, Wiley Online Library on [11/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
FIGURE 1 | 2019 Updated ACC/AHA Clinical Practice Guideline Recommendation Classification System (table modified from the 2019 ACC/
3 of 23
AHA Clinical Practice Guideline Recommendation Classification System).1,2
American Geriatrics Society
SPECIAL ARTICLE OPEN ACCESS
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
Vera Bittner1 | Sunny A. Linnebur2 | Dave L. Dixon3 | Daniel E. Forman4 | Ariel R. Green5 | Terry A. Jacobson6 |
Ariela R. Orkaby 7 | Joseph J. Saseen8 | Salim S. Virani9,10
1Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama, USA | 2University of Colorado Skaggs School of
Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA | 3Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth
University School of Pharmacy, Richmond, Virginia, USA | 4Department of Medicine (Divisions of Geriatrics and Cardiology), University of Pittsburgh and
Pittsburgh Geriatrics, Research, Education, and Clinical Center (GRECC), VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA | 5Division
of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA | 6Lipid Clinic and Cardiovascular
Risk Reduction Program, Department of Medicine, Emory University, Atlanta, Georgia, USA | 7 New England Geriatric Education, Research and Clinical
Center (GRECC), VA Boston Health Care System, Division of Aging, Brigham & Women's Hospital, Harvard Medical School, USA | 8Department of
Clinical Pharmacy and Department of Family Medicine, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA | 9Section of Cardiology,
Department of Medicine, The Aga Khan University, Karachi, Pakistan | 10 Texas Heart Institute and Baylor College of Medicine, Houston, Texas, USA
Correspondence: Vera Bittner
Received: 15 August 2024 | Accepted: 7 September 2024
Keywords: hypercholesterolemia | primary prevention | older adult
ABSTRACT
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 cardio-
vascular disease are also limited since most primary prevention trials have included mostly younger patients. Available data sug-
gest 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.
Abbreviations: AGS, American Geriatrics Society; ASCVD, Atherosclerotic cardiovascular disease; CAC, Coronary artery calcium; CI, confidence interval; T2DM, Type 2 Diabetes mellitus;
HR, Hazard ratio; LDL or LDL-C , Low density lipoprotein (− cholesterol); MI, myocardial infarction; NLA, National Lipid Association; NNT, Number needed to treat; non-H DL-C , non-H DL-
cholesterol; OR, Odds ratio; PCE, Pooled cohort equations; SAMS, Statin associated muscle symptoms; U.S., United States.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is
properly cited.
© 2025 The Author(s). Published by Elsevier Inc on behalf of National Lipid Association and John Wiley and Sons Inc. on behalf of American Geriatrics Society. This paper was jointly developed
by Journal of Clinical Lipidology and Journal of the American Geriatrics Society. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style.
Either citation can be used when citing this article.
Journal of the American Geriatrics Society, 2025; 0:1–23 1 of 23
https://doi.org/10.1111/jgs.19398
, 15325415, 0, Downloaded from https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.19398 by EBMG ACCESS - ETHIOPIA, Wiley Online Library on [11/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Preamble Synopsis
Since 2014, the National Lipid Association (NLA) has issued Cross-sectional and prospective cohort studies show that ath-
several scientific statements on key aspects of the manage- erogenic lipoproteins increase with age from early adulthood to
ment of lipids and lipoproteins to prevent cardiovascular the 7th decade, but gradually decrease in subsequent decades.3, 4
disease (https://w ww.l ipid.org/practicetools/documents). This decrease among the oldest old (8th decade and beyond) is
The current Expert Clinical Consensus, focused on the treat- likely multifactorial including survivor bias (i.e., selective mor-
ment of hypercholesterolemia among individuals older than tality at younger ages among those with the highest atherogenic
75 years without clinically manifest atherosclerotic cardio lipoprotein levels) and declines in cholesterol associated with
vascular disease (ASCVD), was developed as a collaboration co-morbidities (e.g., heart failure, malignancies, malnutrition).
between the NLA and the American Geriatrics Society (AGS). Many studies have shown strong and graded associations be-
The governing bodies of both organizations appointed mem- tween LDL-C level and incident ASCVD in women and men and
bers with relevant expertise to the writing group which was across ethnicities among young and middle-aged populations.
jointly chaired by a representative of NLA (V. B.) and AGS In contrast, early epidemiologic analyses among older individ-
(S.A.L.). The Expert Clinical Consensus was developed by a uals suggested an inverse association between total cholesterol
diverse group of clinical lipidologists, cardiologists, geriatri- and outcomes which is most consistent with reverse causation.5
cians, and pharmacists with cumulative expertise in clinical More contemporary analyses suggest that the association of
medicine, geriatrics, cardiology, endocrinology, pharmacol- LDL-C level to incident ASCVD is maintained in the oldest age
ogy, clinical trials, epidemiology, health outcomes research, groups.6
and public health.
Recommendation-specific supportive text
The chairs and members of the writing group jointly devel-
oped a set of key clinical questions to be addressed by the In 2007, a meta-analysis of 61 prospective studies analyzed isch-
panel. Once the key clinical questions were agreed upon, writ- emic heart disease mortality as a function of total cholesterol or
ing assignments were jointly determined by the group based non-high-density lipoprotein cholesterol (non- HDL- C) strati-
on content expertise with a primary and secondary author fied by sex and age (5th to 9th decade).7 Relative risk of ischemic
assigned to each question. The literature was reviewed and heart disease mortality related to the level of total cholesterol or
recommendations were developed using the 2019 Update of non-HDL-C was highest among 40-49 year-olds. Relative risk de-
the American Heart Association (AHA) / American College creased in a graded fashion with each advancing decade, but it
of Cardiology (ACC) rating system for clinical guidelines, remained statistically significant to age 80-89 years. In contrast,
assigning a Class of Recommendation (I-III) and a Level of absolute risk was lowest in the youngest age group and increased
Evidence (A-C with sub categories) for each recommenda- with advancing age.
tion (Figure 1).1, 2 Each section and its associated recom-
mendations were discussed in detail by the writing group. The prospective Copenhagen General Study investigated the
Preliminary recommendations were presented at the Annual association of LDL- C with incident myocardial infarction
Scientific Meeting of AGS (AGS23) in May 2023 and feedback (MI) and ASCVD in 91,131 participants ranging in age from
from the audience was incorporated as appropriate. Final 20-100 years old; 10,591 participants were 70-79 years old and
recommendations based on consensus of at least 60% of the 3,188 participants were 80-100 years old.6 Higher LDL-C was
expert panel were then reviewed by external peer reviewers, predictive of incident MI and ASCVD independent of age. As in
edited as appropriate and approved by the respective Boards of the Prospective Studies Collaboration, relative risks of MI and
the NLA and AGS on 9/20/2024. ASCVD (expressed as adjusted hazard ratios (HRadj)) were
highest in the youngest (20-49 year-old) age group (MI HRadj
1.68 (95% CI 1.45-1.87); ASCVD HRadj 1.47 (95% CI 1.32-1.64))
and lowest in the oldest (80-100 year-old) age group (MI HRadj
1.28 (95% CI 1.08-1.52); ASCVD HRadj 1.16 (95% CI 1.05-1.29)).
By contrast, absolute risk of events was lowest in the youngest
QUESTION 1 | For the population of adults older than 75 years age group and highest in the oldest age group. Based on these
without established ASCVD, what is the association between prospective observational data, the authors estimated the num-
low-density lipoprotein cholesterol (LDL-C) and incident ASCVD? ber needed to treat (NNT) to prevent MI or ASCVD for every
1 mmol/L (38.67 mg/dL) lowering of LDL-C over 5 years. The
estimated NNT declined with each decade of age (Figure 2).
For ASCVD, the estimated NNT for 80-100 year-old partici-
pants was 42 compared to 345 for 50-59 year-old participants;
for MI, the respective estimated NNTs were 80 and 439. Thus,
LDL-C is an important risk factor among patients older than
75 years and should be measured for ASCVD risk stratification.
2 of 23 Journal of the American Geriatrics Society, 2025
,15325415, 0, Downloaded from https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.19398 by EBMG ACCESS - ETHIOPIA, Wiley Online Library on [11/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
FIGURE 1 | 2019 Updated ACC/AHA Clinical Practice Guideline Recommendation Classification System (table modified from the 2019 ACC/
3 of 23
AHA Clinical Practice Guideline Recommendation Classification System).1,2
