Journal of Gerontological Nursing

Feature Article Supplemental Data

Hypercholesterolemia Management in Older Adults: A Scoping Review of Recent Evidence

Harleah G. Buck, PhD, RN, FPCN, FAHA, FAAN; Stephen Mcghee, DNP, MSc, PGCE, RNT, RN, VR; Randall L. Polo, JD, MA; Cheryl Zambroski, PhD, RN

Abstract

Given the high co-occurrence of age and hypercholesterolemia, there is a critical need for age-appropriate evidence for achieving normal cholesterol levels. The purpose of the current review was to map recent evidence (i.e., past 5 years) on hypercholesterolemia management in older adults and identify gaps in the evidence. Electronic searches in PubMed, CINAHL, and Scopus were conducted. Inclusion criteria were age 65 or older and lipid panel outcome. Exclusion criteria were a mixed age sample and familial hypercholesterolemia. An initial pool of 3,176 unique records resulted in 26 articles that met inclusion criteria. Arksey and O'Malley's scoping study framework was used. Sample sizes ranged from 12 to 1,010 (N = 8,509) adults ages 65 to 96. Evidence supports the use of exercise, diet, and statins in older adults. Laboratory, intervention, and methodological gaps were identified. Much remains to be examined in safely managing older adults with hypercholesterolemia, including determining time to behavior change in nonpharmacological interventions and contextual factors influencing adherence. [Journal of Gerontological Nursing, 45(3), 31–42.]

Abstract

Given the high co-occurrence of age and hypercholesterolemia, there is a critical need for age-appropriate evidence for achieving normal cholesterol levels. The purpose of the current review was to map recent evidence (i.e., past 5 years) on hypercholesterolemia management in older adults and identify gaps in the evidence. Electronic searches in PubMed, CINAHL, and Scopus were conducted. Inclusion criteria were age 65 or older and lipid panel outcome. Exclusion criteria were a mixed age sample and familial hypercholesterolemia. An initial pool of 3,176 unique records resulted in 26 articles that met inclusion criteria. Arksey and O'Malley's scoping study framework was used. Sample sizes ranged from 12 to 1,010 (N = 8,509) adults ages 65 to 96. Evidence supports the use of exercise, diet, and statins in older adults. Laboratory, intervention, and methodological gaps were identified. Much remains to be examined in safely managing older adults with hypercholesterolemia, including determining time to behavior change in nonpharmacological interventions and contextual factors influencing adherence. [Journal of Gerontological Nursing, 45(3), 31–42.]

Approximately 6.5 million individuals, the majority of whom are older adults, currently live with heart failure (HF) (Benjamin et al., 2017). This number is projected to increase 46% (8,000,000) by 2030 if measures are not taken to address this public health issue (Benjamin et al., 2017). HF is a common endpoint of cardiovascular disease (CVD), of which hypercholesterolemia, or the presence of excess cholesterol in the blood, can be the common starting point (Jellinger et al., 2017; Jessup & Brozena, 2003; Yancy et al., 2017).

Maintaining a healthy cholesterol level (a molecule essential for life) is part of the American Heart Association's Life's Simple 7 campaign (avoid tobacco and maintain healthy physical activity, diet, weight, cholesterol, blood pressure, and glucose levels). Nevertheless, one in eight adults in the United States have total cholesterol levels ≥240 mg/dL (Centers for Disease Control and Prevention, 2017). The number of adults with hypercholesterolemia only rises with age (National Center for Health Statistics, 2017). To reduce the incidence, and even prevent HF, hypercholesterolemia must be treated.

Given the high co-occurrence of age and hypercholesterolemia (Luo et al., 2014), there is a critical need to examine age-appropriate evidence for achieving and maintaining normal levels of cholesterol. Prevalence of common secondary causes of hypercholesterolemia (e.g., hypothyroidism, chronic renal disease) also increases with age, once again putting older adults at higher risk for sequelae such as stroke and myocardial infarction (Jellinger et al., 2017). Current guidelines suggest annual screening for older men and women (Grundy et al., 2018; Jellinger et al., 2017). But once cholesterol is assessed, what treatments should be suggested for those whose levels are higher than the normal range?

Determining appropriate treatments is made difficult by the historic and ongoing exclusion of older adults from clinical trials (Dunn, Wilson, & Sitas, 2017; Herrera et al., 2010) or from including them but then not examining the effect of age on outcomes. One recent systematic review and meta-analysis serves as an example of these issues. Investigators examined the effect of exercise on cholesterol, but only 13 (8%) of 160 randomized clinical trials had samples that were clearly identified as older adults (defined herein as age ≥65 years) (Lin et al., 2015). Further, for the meta-analysis, participants were dichotomized as ages >50 or <50, once again, masking potential unique older adult responses to the interventions. This difficulty in distinguishing older adult–specific hypercholesterolemia evidence led the current authors to develop a project that would rigorously review the most recent literature on hypercholesterolemia in older adults and develop a series of clinically meaningful articles related to patient care for baccalaureate and advanced practice nurses as well as identify gaps in the evidence base to inform researchers.

The current article reports the results of the gap analysis conducted via a scoping review. Scoping reviews summarize and synthesize the evidence (literature) on a topic to inform practice, policy, and future directions by mapping the literature (Levac, Colquhoun, & O'Brien, 2010). This method was considered particularly suited to the current project. Therefore, the purpose of this scoping review on hypercholesterolemia management in older adults was to map the most recent evidence (i.e., the past 5 years) and identify gaps in the literature to inform practice and research.

Method

Arksey and O'Malley's (2005) framework (Levac et al., 2010) provided the methodological structure for the scoping review. As such, research questions were composed, relevant studies most salient to the questions were identified, the extraction form was developed (i.e., data were charted), and findings were summarized. A scoping review methodology was selected as the aims were fairly broad, the research questions were developed during the review, all study types with data were included, and data were “charted” according to the study aims rather than synthesizing and aggregating findings as would have been done in a systematic review (Munn et al., 2018).

Identifying the Research Questions

The current group of CVD experts were interested in assessing the strength of the evidence for the clinical management of older adults with hypercholesterolemia to be able to teach, conduct research, and practice considering the best evidence. To achieve these goals, a scoping review was performed to allow the mapping of multiple studies in such a way that the extent of what is known on hypercholesterolemia management was easily seen while identifying gaps in the evidence base. The research questions were: (a) What are evidence-based strategies for managing hypercholesterolemia in older adults, and (b) What are the gaps in the evidence related to managing hypercholesterolemia in older adults?

Identifying Relevant Studies

The authors' intent was to fully capture the recent (i.e., past 5 years) literature across disciplines—nursing, medicine, pharmacy, public health—related to hypercholesterolemia in older adults. Preliminary search strategies were developed and tested to identify high-quality, databased articles, such as meta-analyses, systematic reviews, randomized clinical trials, and clinical guidelines.

Inclusion/Exclusion Criteria. Study inclusion criteria were: adults age ≥65 years; human studies; English language articles; study outcome variable must be from a lipid panel; professional society guidelines; and observational studies, clinical trials, meta-analyses, and systematic reviews published between 2013 and 2018. Studies were excluded if they involved: familial hypercholesterolemia; mixed animal/human studies; mixed age samples (i.e., included participants younger than 65 if a range was given or a mean age ≤65 with a standard deviation that indicated participants were younger than 65); or were duplicate studies, case reports, opinion pieces, editorials, and letters to the editor.

Data Sources and Search Strategy. Electronic searches were developed and performed by a medical librarian (R.L.P.) in PubMed, CINAHL, and Scopus. The search strategy was developed in PubMed and then translated into CINAHL and Scopus using each database platform's unique controlled vocabulary, command language, search fields, and limit filters. MeSH terms, CINAHL headings, and keywords were used to search for interventions published in the past 5 years that focused on managing hypercholesterolemia in the older adult population. All searches were executed and results downloaded to an EndNote library on March 26, 2018. The complete search strategies (without application of limit filters described below) can be found in Table A (available in the online version of this article).

Table A:

The PubMed search was limited by: English language; date range (March 1, 2013 to present); and publication type (Practice Guideline, Meta-Analysis, Systematic Reviews, Randomized Controlled Trial, and Controlled Trial). The CINAHL search was limited by: English language; date range (March 2013 to present); and publication type (Practice Guidelines, Meta-Analysis, Systematic Review, Randomized Controlled Trial, and Controlled Trial). The Scopus search was limited by: English language; date range (2013 to 2018); and publication type (Articles or Reviews).

The search strategies, with applied limits, yielded a total of 3,369 article records, which were exported to EndNote. EndNote's duplicate finder feature was used to identify and remove 193 duplicate article records. After removal of duplicate records, 3,176 unique article records were yielded for performance of the inclusion/exclusion (protocol) analysis needed to identify the final set of articles comprising the corpus of the scoping review analysis (Figure 1).

Process for selecting hypercholesterolemia studies using PRISMA guidelines (Moher, Liberati, Tetzlaff, & Altman, 2009).

Figure 1.

Process for selecting hypercholesterolemia studies using PRISMA guidelines (Moher, Liberati, Tetzlaff, & Altman, 2009).

Study Selection

Title and Abstract Screening. In the first round, screening the 3,176 articles was divided among authors. The screening spreadsheet was pre-populated with author, publication year, article title, abstract, and exclusion criteria. Directions included reviewing the title/abstract using the protocol criteria, excluding the article on the first screening if exclusion criteria were identified, including the article only if no exclusion criteria were present, and, when in doubt, retaining the article for the next level of screening. For example, if there was no abstract and the title was ambiguous, the screener was instructed to retain the study for further review. The lead author (H.G.B.) reviewed the completed spreadsheet of each reviewer. At this stage, 217 studies were retained. Due to the large amount of retained studies, the team decided to retrain on the inclusion and exclusion criteria and conduct a second round of title/abstract screening using the same criteria as the previous round. The 217 studies were divided among authors with each receiving a different pool of articles from their previous screen. This round resulted in 52 articles advancing to full-text screening.

Full-Text Screening. Articles were divided among authors with effort made to give each author a new set of articles to examine. After full texts of the articles were obtained, the inclusion/exclusion criteria were again applied. After the spreadsheets were completed, the lead author once again reviewed them for consistency with the protocol and other authors' screenings. Twenty-six articles met the study criteria and were accepted into the final review.

Charting the Data

Data Abstraction and Management. Per the study protocol, the team developed a data abstraction spreadsheet to capture the data needed to answer the research questions. This abstraction spreadsheet included four study domains (i.e., publication, study design, intervention elements, and patient outcomes). Definitions of each characteristic within each domain and an example article were abstracted in-full into the spreadsheet to increase the reliability of data abstraction. Several data abstraction practice sessions were also held. Once each team member had completed his/her abstraction, it was confirmed by a second team member and finally by the full team. This confirmation resulted in consensus on the accepted articles and information abstraction. In keeping with the methodology (Arksey & O'Malley, 2005), quality of evidence was not assessed.

Collating, Summarizing, and Mapping the Results

Using the completed data abstraction spreadsheet, data needed to answer the research questions were copied to a new sheet in the spreadsheet, which contained study identification information (i.e., authors) and the domain under examination. For example, to answer the first question, a new sheet was created with columns for author names and intervention components. Data were collated and mapped using a realist review framework (Wong, Greenhalgh, Westhorp, Buckingham, & Pawson, 2013). To establish the evidence base, all interventions and their outcomes were examined using qualitative meta-synthesis techniques (Sandelowski, 2001, 2010), which involved identifying, counting, and categorizing the intervention components and examining patterns in the categories by patient outcomes. Similarly, when all interventions were identified to answer the second question, as a team the authors' asked, “What is missing?” using similar literature from other populations or diseases. This analytic phase was iterative and continued until no further gaps were identified.

Results

Study Demographics

The 26 articles in the current review were published between 2013 and 2017. Eight studies were conducted in the Americas (North and South), eight in Europe/Middle East, and 10 in Australasia, providing a global assessment of the hypercholesterolemia evidence. Table 1 provides the details of the seven non-randomized (Bruseghini et al., 2015; Constance et al., 2014; Luo et al., 2014; Malin, Navaneethan, Mulya, Huang, & Kirwan, 2014; Mosca et al., 2014; Park et al., 2014; Zou & Si, 2013) and 11 randomized (Chen et al., 2014; Davis, Bryan, Hodgson, Woodman, & Murphy, 2017; Hunger et al., 2015; Lúcio Mazini Filho et al., 2013; Nishida et al., 2015; Normandin, Chmelo, Lyles, Marsh, & Nicklas, 2017; Oliveras-Lopez et al., 2013; Sibley et al., 2013; So et al., 2013; Stender, Budinski, Gosho, & Hounslow, 2013; Vorup, Pedersen, Melcher, Dreier, & Bangsbo, 2017) trials. In addition to the interventions, the literature search resulted in five observational studies (Alaghehband et al., 2017; Blekkenhorst et al., 2015; Ferguson et al., 2016; Jacobs, Cohen, Ein-Mor, & Stessman, 2013; Lv et al., 2016), two guidelines (Jellinger et al., 2017; Klose et al., 2014), and one evidence review (Lin et al., 2014). The guidelines and review were used as references but not used to answer the research questions due to their inclusion of participants younger than 65. The intervention and observational studies that were analyzed included sample size ranges of N = 12 for an Italian proof-of-concept exercise study (Bruseghini et al., 2015) to N = 1,010 in the secondary analysis of the ZETELD drug trial (Constance et al., 2014). In total, 8,509 participants ages 65 to 96 were included in the studies, with 52% of participants ages 65 to 74 and 22% of participants ages 75 to 84. Only one study had a mean age of 85.8 (Lv et al., 2016), signifying a sample of the oldest old. This observational study examined a cross-section of 2,000 participants from the Chinese Longitudinal Healthy Longevity Survey for association of serum cholesterol with cognitive status (Lv et al., 2016). Seven studies had populations that were >50% male, 11 studies had populations >50% female, and the remainder had relatively equal samples.

Intervention Study InformationIntervention Study InformationIntervention Study Information

Table 1:

Intervention Study Information

Evidence-Based Strategies for Managing Hypercholesterolemia in Older Adults

Three observational studies in the dataset examined the relationships between diet and lipid levels (Alaghehband et al., 2017; Blekkenhorst et al., 2015; Ferguson et al., 2016) and found mixed relationships between certain dietary fatty acids and lipid levels. These studies were secondary analyses or sub-studies of larger clinical trials or national datasets. A fourth observational study examined the relationship of lipids and cognitive impairment (Lv et al., 2016), where cholesterol levels in the high/normal range were associated with higher Mini-Mental State Examination scores. The fifth observational study examined the relationship of total cholesterol and mortality in statin and non-statin groups formed from a longitudinal birth cohort dataset, finding a consistent lack of association between total cholesterol levels and all-cause mortality (Jacobs et al., 2013).

Intervention categories included drug, exercise, nurse case management, and device studies, which can be grouped into nonpharmacological and pharmacological management techniques (Table 2). The drug studies examined the efficacy of statins plus adjuvant drugs (i.e., niacin [Sibley et al., 2013], fibrates [Zou & Si, 2013], ezetimibe [Constance et al., 2014; Luo et al., 2014], and policosanol [Zou & Si, 2013]), statin versus statin (Stender et al., 2013), statin versus no statin (Jacobs et al., 2013), and statin versus lifestyle guidance (Chen et al., 2014). All drug studies reported positive outcomes. Taken together, the evidence supports the use of statins in older adults.

Nonpharmacological and Pharmacological Treatment Evidence by Lipid TestNonpharmacological and Pharmacological Treatment Evidence by Lipid TestNonpharmacological and Pharmacological Treatment Evidence by Lipid Test

Table 2:

Nonpharmacological and Pharmacological Treatment Evidence by Lipid Test

In the nonpharmacological category, exercise interventions comprise the largest category. Exercise studies examined the efficacy of resistance training (Bruseghini et al., 2015; Normandin et al., 2017; So et al., 2013), team games (Vorup et al., 2017), treadmill and/or cycling (Bruseghini et al., 2015; Malin et al., 2014), step exercise (Nishida et al., 2015), and walking (Park et al., 2014; Lúcio Mazini Filho et al., 2013). Similar to the drug trials, there was only one null exercise trial, which showed no change in total cholesterol, triglycerides, and high-density lipoprotein (HDL) in a 12-week resistance band intervention (So et al., 2013). Dietary studies examined calorie restriction (Normandin et al., 2017), Mediterranean diet (Davis et al., 2017), and substitution of extra virgin olive oil for usual dietary fats (Oliveras-Lopez et al., 2013). The one nurse case management/home follow-up study (i.e., in-person visits and phone calls for 12 months) (Hunger et al., 2015) had mixed results with a significant decrease in low-density lipoprotein but no change in the total cholesterol/ HDL ratio after 12 months. The device study (Mosca et al., 2014) involved bundling multiple medications in a blister pack, but improvements in lipid levels became non-significant when time with a pharmacist was added to the model. Taken together, the evidence supports the use of certain exercise and dietary interventions while suggesting further study is needed regarding case management and bundling medications.

Gaps in the Evidence Related to Managing Hypercholesterolemia in Older Adults

Careful examination of the studies in the current review revealed several gaps in outcomes, interventions, and methodology in the evidence. The outcome gaps are primarily related to the more recent lipid metrics (e.g., apolipoprotein B, very-low density lipoprotein) (Table 1). The current search resulted in few studies that reported either positive or null outcomes for these metrics.

Intervention gaps were also identified. No technology studies targeting hypercholesterolemia were found. Given that all hypercholesterolemia clinical guideline recommendations begin with lifestyle adjustments, coupled with the explosion in technology trials, it was surprising that the search did not return any lifestyle modification technology trials in which lipids were an outcome. Studies examining mind/body interventions, such as yoga, tai chi, or mindfulness, were also missing from the nonpharmacological literature. Other intervention gaps involved the lack of examination of other dietary interventions (e.g., vegan diets) or pro-social behavioral interventions (e.g., peer coaching). Although a direct causal pathway between these techniques and lipid metabolism may not be present, hypercholesterolemia could be indirectly affected through other mechanisms such as adherence to recommendations or self-efficacy.

Identified methodological gaps involved the lack of qualitative studies in which the patient experience of factors surrounding lipid self-management was characterized or examined for contextual elements. Similarly missing are studies that examined intra-individual variability in self-management via ecological momentary assessment. Because dietary and medication adherence are integral to managing lipid levels, this type of examination is necessary. Finally, a noted gap is lack of standardization on how much time is needed for nonpharmacological interventions to change lipid levels. For example, in two dietary interventions, one involved a 6-week trial replacing normal fats with extra virgin olive oil (Oliveras-Lopez et al., 2013), whereas the other trialed a 6-month Mediterranean diet (Davis et al., 2017). Neither study offered an explanation for the trial duration. Determining time to blood level change is critical given that guidelines recommend lifestyle changes first followed by aggressive pharmacological treatment for individuals at risk for cardiac events (Jellinger et al., 2017). The time required to allow lifestyle changes to work before prescribing medication is currently unknown.

Discussion

The purpose of the current scoping review was to map the most recent (i.e., within the past 5 years) hypercholesterolemia evidence to inform practice and research and identify gaps in the literature as they relate to older adults. In doing so, it has been established that although studies targeting older adults are few compared with younger adult studies, there is some evidence on which practice decisions can be made. Table 1 and Table 2 map the recent literature in terms of study information and pharmacological and nonpharmacological treatment evidence by lipid test for clinicians and researchers.

Mapping the Evidence

Nonpharmacological and pharmacological evidence was found for addressing hypercholesterolemia in older adults. Although hypercholesterolemia management guidelines are provided by multiple internal medicine disciplines, the search terms resulted in identifying the American Association of Clinical Endocrinology dyslipidemia guidelines (Jellinger et al., 2017). Endocrinology is particularly focused on lipid management because of the increased risk of CVD and metabolic syndrome in dyslipidemia. The guidelines acknowledged a 30-year improvement in national lipid levels; however, they also noted that increasing numbers of older adults and the link between advancing age and CVD calls for continued vigilance. The guideline recommends that adults older than 65 be screened annually. But beyond this suggestion, treatment recommendations are for personalized treatment with a comprehensive strategy of lifestyle changes and pharmacotherapy. These guidelines do not address specific age-related challenges. For example, statins and omega-3 fatty acids are known to impair liver function, cause muscle weakness, and increase the likelihood of drug-to-drug interactions (Jellinger et al., 2017). Older adults who are more likely to have impaired end organs, be at greater fall risk, and experience polypharmacy must be managed cautiously when prescribing certain medications. In addition, older adults may be at increased risk of adverse events, such as developing diabetes (Carter et al., 2013) or death with certain statins (Wenger, Lewis, Herrington, Bittner, & Welty, 2007). The current review adds to previous work as it identified recent, age-specific nonpharmacological and pharmacological trials for a clinician to reference in clinical decision making.

A further age-specific consideration highlighted in the current analysis is whether enough time is given for response to nonpharmacological interventions before older adults are placed on medication. The analysis showed that there was no standard intervention time overall, ranging from 6 weeks (Oliveras-Lopez et al., 2013) to 6 months (Davis et al., 2017) in the same category (i.e., diet). Therefore, the amount of time a clinician should continue to encourage exercise, diet, or other lifestyle changes for older adults before prescribing medication is unknown. Given the cautions mentioned in the clinical guidelines concerning statins, this question must be answered.

Mapping the Gaps

Gaps were identified in three categories—laboratory, intervention, and methodology. Even with the literature search restricted to the past 5 years, few studies were found that provided evidence on some of the newer, more specific tests now used in practice. Further examination should be given to expanding this evidence base. There are also gaps related to managing patients using technology, mind/body techniques, or diet beyond restricting fat type or amount. Given the direction in which chronic illness management is headed, evidence is needed regarding efficacy and effectiveness of techniques that are increasing in prevalence. Important methodological gaps were also identified. The current search did not result in any qualitative studies or studies that examined intra-individual variability or standardized intervention times.

Implications for Practice and Research

The current findings have implications for practice and research. First, clinicians should familiarize themselves with the studies reviewed, as they provide a recent evidence base against which to compare their patients. However, before applying any evidence to practice, clinicians should carefully examine the study sample. The patient that the drug or intervention was tested on may not be the same as the patient being examined. The judicious application of evidence coupled with rigorous clinical decision making is necessary. Second, the gaps identified in the evidence should suggest next steps for any researcher. Much remains to be examined in safely managing older adults with hypercholesterolemia. Contextual factors influencing adherence to either lifestyle or pharmacological recommendations should be examined, and the question of how much time it takes to change behavior in nonpharmacological interventions must be answered.

Limitations

Several caveats should be kept in mind while reviewing this article. First, with most studies reporting positive effects on patient outcomes, the presence of publication bias is suggested; however, this bias was not assessed as it is not part of the scoping review methodology. Second, in focusing on the most recent evidence, important earlier studies were not included. However, retaining the guidelines and reviews provided a concise compilation of best practices against which to evaluate these newer studies. Finally, the search terms and inclusion criteria, although carefully selected and tested, may have resulted in unintended biases.

Conclusion

Recent literature related to hypercholesterolemia management in older adults was examined and synthesized and meaningful gaps in the evidence, which need to be addressed, were identified. To prevent the common endpoint of CVD and HF, hypercholesterolemia must be addressed in older adults.

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Intervention Study Information

Study/CountryMean Participant AgeStudy Design/Sample SizeIntervention TypeIntervention DetailsLipid Outcomes
Bruseghini et al. (2015) Italy70Cohort Pre/post N = 12ExerciseAerobic interval training and isoinertial resistance training in an 8-week trialIsoinertial resistance training reduced LDL and TC Aerobic interval training did not reduce LDL and TC
Chen et al. (2014) China80Randomized to one of two intervention arms N = 64DrugAtorvastatin 10 mg/day and lifestyle guidance versus lifestyle guidance only in a 12-month trialAtorvastatin + lifestyle group showed significant reduction of TG and LDL versus lifestyle only
Constance et al. (2014) United States, Russia, Ukraine, Canada, Romania, Poland71Secondary analysis of ZETELD trial; randomization in parent study was stratified based on baseline LDL-C levels and the presence or absence of CVD N = 1,010DrugAtorvastatin 10 mg plus ezetimibe 10 mg daily versus atorvastatin 20 mg daily for 6 weeks followed by participants in the ezetimibe group continuing on the same treatment for an additional 6 weeks while participants in the atorvastatin 20 mg group were up titrated to 40 mg for an additional 6 weeks in a 12-week trialCombination 10 mg atorvastatin and ezetimibe was more effective at reaching LDL, non-HDL, and Apo B targets than up titration of atorvastatin alone
Davis, Bryan, Hodgson, Woodman, & Murphy (2017) Australia71RCT N = 166DietMediterranean diet versus usual diet in a 6-month trialSignificant reduction in TG in Mediterranean diet No effect on TC, LDL, or HDL
Lúcio Mazini Filho et al. (2013) Brazil68RCT Pre/post analysis N = 54ExerciseWalking, stretching, and balance exercise group versus usual activity in a 16-week trialExercise group reduced TG, LDL, and TC, and increased HDL Control group TC also reduced
Hunger et al. (2015) Germany75RCT N = 329Case managementNurse-led case management program (live and telephone education and guidance) versus usual care in a 12-month trialCase management reduced LDL No difference in TC/HDL ratio
Luo et al. (2014) China67Non-randomized to one of two intervention arms N = 84DrugAtorvastatin 20 mg and ezetimibe 10 mg versus atorvastatin only in a 12-month trialCombination atorvastatin and ezetimibe was more effective at lowering LDL
Malin, Navaneethan, Mulya, Huang, & Kirwan (2014) United States66Cohort Pre/post N = 30ExerciseTreadmill, walking, and cycling intervention in a 12-week trialExercise reduced TC and TG
Mosca et al. (2014) Portugal72Self-selected into one of two groups Pre/post N = 54DeviceMedications via blister pack versus usual dispensingHDL improved with bivariate analysis, but improvement disappeared when time with pharmacist was controlled
Nishida et al. (2015) Japan70RCT N = 62ExerciseBench step exercise versus normal activity in a 12-week trialStep increased HDL in participants with lower baseline HDL
Normandin, Chmelo, Lyles, Marsh, & Nicklas (2017) United States70Randomized to one of two intervention arms N = 126Exercise and dietResistance training + calorie reduction versus resistance training only in a 5-month trialResistance training + calorie reduction reduced VLDL and TG
Oliveras-Lopez et al. (2013) Spain81RCT N = 62DietDietary intervention with olive oil versus normal diet in a 6-week trialOlive oil reduced TC, LDL, and TG and increased HDL
Park et al. (2014) Japan70Non-randomized to one of two groups Pre/post N = 28ExerciseWalking versus usual activity in a 12-week trialWalking lowered LDL but not TG, TC, or HDL
Sibley et al. (2013) United States72.5Randomized to one of two intervention arms N = 117DrugExtended release niacin or placebo titrated to a target dose of 1,500 mg daily + statins versus statins only in a 12-week trialStatin + niacin increased HDL
So et al. (2013) Korea70RCT N = 40ExerciseResistance band exercise intervention versus usual activity in a 12-week trialResistance exercise did not change TC, TG, and HDL
Stender, Budinski, Gosho, & Hounslow (2013) Denmark, Germany, Israel, the Netherlands, and United Kingdom70Randomized to one of two intervention arms N = 760DrugPitavastatin (1, 2, and 4 mg) and placebo versus pravastatin tablets (10, 20, and 40 mg) and placebo in an 18- to 20-week parallel group trialCompared with pravastatin, pitavastatin provided greater decreases in total cholesterol and Apo B in all dose groups and TG in the low-dose and higher-dose groups, and greater increases in HDL in the intermediate-dose groups
Vorup, Pedersen, Melcher, Dreier, & Bangsbo (2017) Denmark70Randomized to one of two intervention arms N = 39ExerciseFloorball (vigorous) team games versus petanque (quieter) team games in a 12-week trialFloorball reduced plasma LDL and TG, petanque did not reduce LDL or TG
Zou & Si (2013) China81Non-randomized Pre/post N = 450DrugTreatment groups: niacin + fibrates; statin + niacin; statin + fibrates; statin + policosanol; and statin + ezetimibe in a 6-month trialStatin + ezetimibe most effective in lowering TC and LDL levels from baseline Niacin + fibrates most effective in decreasing TG and increasing HDL levels from baseline

Nonpharmacological and Pharmacological Treatment Evidence by Lipid Test

Lipid TestNonpharmacological EvidencePharmacological Evidence
Total cholesterol (TC)Aerobic interval training and isoinertial resistance training reduced TC in an 8-week trial (Bruseghini et al., 2015) Walking, stretching, and balance exercise reduced TC in a 16-week trial (Lúcio Mazini Filho et al., 2013) Treadmill, walking, and cycling intervention reduced TC in a 12-week trial (Malin, Navaneethan, Mulya, Huang, & Kirwan, 2014) Dietary intervention with olive oil reduced TC in a 6-week trial (Oliveras-Lopez et al., 2013) A resistance band exercise program did not reduce TC in a 12-week trial (So et al., 2013)Pitavastatin had greater effect than pravastatin on reducing TC in a 12-week trial (Stender, Budinski, Gosho, & Hounslow, 2013) Statin and ezetimibe reduced TC in a 6-month trial (Zou & Si, 2013)
High-density lipoprotein (HDL)Walking, stretching, and balance exercise increased HDL in a 16-week trial (Lúcio Mazini Filho et al., 2013) Bench step exercise increased HDL in a 12-week trial (Nishida et al., 2015) Resistance training + calorie reduction increased HDL in a 5-month trial (Normandin et al., 2017) Dietary intervention with olive oil increased HDL in a 6-week trial (Oliveras-Lopez et al., 2013)Statins + niacin increased HDL more when compared with statins only in a 12-week trial (Sibley et al., 2013) Pitavastatin had greater effect than pravastatin on increasing HDL in a 12-week trial (Stender et al., 2013) Statin and ezetimibe increased HDL in a 6-month trial (Zou & Si, 2013)
Low-density lipoprotein (LDL)Aerobic interval training and isoinertial resistance training reduced LDL levels in an 8-week trial (Bruseghini et al., 2015) Mediterranean diet reduced LDL in a 6-month trial (Davis, Bryan, Hodgson, Woodman, & Murphy, 2017) Walking, stretching, and balance exercise reduced LDL in a 16-week trial (Lúcio Mazini Filho et al., 2013) Case management reduced LDL in a 12-month trial (Hunger et al., 2015) Walking reduced LDL in a 12-week trial (Park et al., 2014) Dietary intervention with olive oil reduced LDL in a 6-week trial (Oliveras-Lopez et al., 2013) Floorball training reduced LDL in a 12-week trial (Vorup, Pedersen, Melcher, Dreier, & Bangsbo, 2017)Atorvastatin reduced LDL in a 12-month trial (Chen et al., 2014) Combination 10 mg of atorvastatin and ezetimibe was more effective at reducing LDL than up titration of atorvastatin only in a 12-week trial (Constance et al., 2014) Combination of atorvastatin with ezetimibe reduced LDL in a 12-month trial (Luo et al., 2014) Statin and ezetimibe reduced LDL in a 6-month trial (Zou & Si, 2013)
Triglycerides (TG)Mediterranean diet reduced TG in a 6-month trial (Davis et al., 2017) Walking, stretching, and balance exercise reduced TG in a 16-week trial (Lúcio Mazini Filho et al., 2013) Dietary intervention with olive oil reduced TG in a 6-week trial (Oliveras-Lopez et al., 2013) Treadmill, walking, and cycling intervention reduced TG in a 12-week trial (Malin et al., 2014) Resistance training + calorie reduction reduced TG in a 5-month trial (Normandin et al., 2017) Floorball training reduced TG in a 12-week trial (Vorup et al., 2017)Atorvastatin reduced TG in a 12-month trial (Chen et al., 2014) Pitavastatin had greater effect than pravastatin on reducing TG in a 12-week trial (Stender et al., 2013) Niacin + fibrates reduced TG in a 6-month trial (Zou & Si, 2013)
Apolipoprotein B (Apo B)No evidenceCombination 10 mg of atorvastatin and ezetimibe was more effective at reducing Apo B than up titration of atorvastatin only in a 12-week trial (Constance et al., 2014) Pitavastatin had greater effect than pravastatin on reducing Apo B in a 12-week trial (Stender et al., 2013)
Very low–density lipoprotein (VLDL)Walking, stretching, and balance exercise reduced VLDL in a 16-week trial (Lúcio Mazini Filho et al., 2013) Resistance training + calorie reduction reduced VLDL in a 5-month trial (Normandin et al., 2017)No evidence
PubMed
(((“Cholesterol/blood”[Mesh] OR “Cholesterol, HDL”[Mesh] OR “Cholesterol, LDL”[Mesh] OR “Cholesterol, VLDL”[Mesh] OR “Cholesterol, Dietary”[Mesh] OR “Hypercholesterolemia”[Mesh] OR hypercholesterol*[tiab] OR “high cholesterol”[tiab] OR “elevated cholesterol”[tiab] OR HDL[tiab] OR LDL[tiab] OR VLDL[tiab] OR “high total cholesterol”[tiab] OR “cholesterol guideline”[tiab] OR “cholesterol guidelines”[tiab] OR “cholesterol level”[tiab] OR “cholesterol levels”[tiab] OR “low density lipoprotein cholesterol”[tiab] OR “high density lipoprotein cholesterol”[tiab] OR “very low density lipoprotein cholesterol”[tiab])) AND (“Therapeutics”[MeSH] OR “Disease Management”[Mesh] OR “therapy”[Subheading] OR “Dietary Supplements”[Mesh] OR “Oleic Acid”[Mesh] OR “oleic acid”[tiab] OR “Diet”[Mesh] OR fasting[tiab] OR “reduced saturated fat”[tiab] OR “reduced cholesterol”[tiab] OR “reduced carbohydrate”[tiab] OR “reduced sugar”[tiab] OR “fat restricted”[tiab] OR “low carbohydrate”[tiab] OR “low carb”[tiab] OR “low cholesterol”[tiab] OR “low sugar”[tiab] OR “Complementary Therapies”[Mesh] OR “Exercise”[Mesh] OR “Tai Ji”[Mesh] OR “physical activity”[tiab] OR “physical activities”[tiab] OR “physical conditioning”[tiab] OR “physical fitness”[tiab] OR walk*[tiab] OR jog*[tiab] OR run*[tiab] OR swim*[tiab] OR yoga[tiab] OR “tai chi”[tiab] OR “tai ji”[tiab] OR “Weight Loss”[Mesh] OR “weight control”[tiab] OR “weight loss”[tiab] OR “lose weight”[tiab] OR “Health Behavior”[Mesh] OR “health behavior”[tiab] OR “health behaviors”[tiab] OR “Healthy Lifestyle”[Mesh] OR lifestyle[tiab] OR “life style”[tiab] OR therap*[tiab] OR manage[tiab] OR managed[tiab] OR managing[tiab] OR management[tiab] OR interven*[tiab] OR treat*[tiab] OR nursing[tiab] OR prevent*[tiab] OR non-pharmacolog*[tiab] OR nonpharmacolog*[tiab] OR “complementary medicine”[tiab] OR “alternative medicine”[tiab] OR exercis*[tiab] OR diet[tiab] OR dietary[tiab] OR probiotic*[tiab] OR “stanols”[tiab] OR “omega 3”[tiab] OR “omega 6”[tiab] OR “Fish Oils”[Mesh] OR “fish oil”[tiab] OR “fish oils”[tiab] OR “Herbal Medicine”[Mesh] OR herbs[tiab] OR herbal[tiab] OR “red yeast rice”[tiab] OR “red yeast rice” [Supplementary Concept] OR statin*[tiab] OR “Hydroxymethylglutaryl-CoA Reductase Inhibitor”[tiab] OR “Hydroxymethylglutaryl-CoA Reductase Inhibitors”[tiab] OR “Anticholesteremic Agents”[Mesh] OR “Anticholesteremic Agents” [Pharmacological Action] OR “Hydroxymethylglutaryl-CoA Reductase Inhibitors”[Pharmacological Action] OR anticholesteremic*[tiab] OR hypocholesteremic*[tiab] OR “cholesterol inhibitors”[tiab] OR “cholesterol lowering”[tiab] OR “cholesterol reducing”[tiab] OR “cholesterol reduction”[tiab] OR “lower cholesterol”[tiab])) AND (“Aged”[MeSH] OR “the aged”[tiab] OR “aged adults”[tiab] OR “aged patients”[tiab] OR “65 years”[tiab] OR “65+ years”[tiab] OR “65 and over”[tiab] OR “65 and older”[tiab] OR “above 65”[tiab] OR “over 65”[tiab] OR elder*[tiab] OR geriatric[tiab] OR “older adult”[tiab] OR “older adults”[tiab] OR senior*[tiab] OR “oldest old”[tiab] OR “old age”[tiab] OR “older patients”[tiab] OR “70 years”[tiab] OR “70+ years”[tiab] OR “70 and over”[tiab] OR “70 and older”[tiab] OR “above 70”[tiab] OR “over 70”[tiab] OR “75 years”[tiab] OR “75+ years”[tiab] OR “75 and over”[tiab] OR “75 and older”[tiab] OR “above 75”[tiab] OR “over 75”[tiab] OR “80 years”[tiab] OR “80+ years”[tiab] OR “80 and over”[tiab] OR “80 and older”[tiab] OR “above 80”[tiab] OR “over 80”[tiab])
CINAHL
((MH “Hypercholesterolemia+”) OR (MH “Cholesterol+”) OR (TI hypercholesterolemia OR AB hypercholesterolemia) OR (TI hypercholesterolaemia OR AB hypercholesterolaemia) OR (TI cholesterol OR AB cholesterol) OR (TI ldl OR AB ldl) OR (TI hdl OR AB hdl) OR (TI vldl OR AB vldl)) AND ((MH “Therapeutics+”) OR (TI therap* OR AB therap*) OR (MH “Disease Management”) OR (TI manage OR AB manage) OR (TI managed OR AB managed) OR (TI managing OR AB managing) OR (TI management OR AB management) OR (TI interven* OR AB interven*) OR (TI treat* OR AB treat*) OR (TI prevent* OR AB prevent*) OR (TI nursing OR AB nursing) OR (MH “Diet+”) OR (TI diet OR AB diet) OR (TI dietary OR AB dietary) OR (TI fasting OR AB fasting) OR (TI “reduced saturated fat” OR AB “reduced saturated fat”) OR (TI reduc* N3 cholesterol OR AB reduc* N3 cholesterol) OR (TI inhibit* N3 cholesterol OR AB inhibit* N3 cholesterol) OR (TI lower* N3 cholesterol OR AB lower* N3 cholesterol) OR (TI “low cholesterol” OR AB “low cholesterol”) OR (TI reduc* N3 carbohydrate OR AB reduc* N3 carbohydrate) OR (TI restrict* N3 fat* OR AB restrict* N3 fat*) OR (TI lower* N3 carbohydrate OR AB lower* N3 carbohydrate) OR (TI “low carbohydrate” OR AB “low carbohydrate”) OR (TI “low carb” OR AB “low carb”) OR (TI reduc* N3 sugar OR AB reduc* N3 sugar) OR (TI lower* N3 sugar OR AB lower* N3 sugar) OR (TI “low sugar” OR AB “low sugar”) OR (MH “Alternative Therapies+”) OR (TI “alternative medicine” OR AB “alternative medicine”) OR (TI “complementary medicine” OR AB “complementary medicine”) OR (MH “Exercise+”) OR (MH “Physical Activity”) OR (MH “Physical Fitness+”) OR (MH “Tai Chi”) OR (MH “Yoga+”) OR (TI “physical activity” OR AB “physical activity”) OR (TI “physical fitness” OR AB “physical fitness”) OR TI (“physical activities” OR AB “physical activities”) OR (TI “physical conditioning” OR AB “physical conditioning”) OR (TI walk* OR AB walk*) OR (TI jog* OR AB jog*) OR (TI run* OR AB run*) OR (TI swim* OR AB swim*) OR (TI “tai chi” OR AB “tai chi”) OR (TI yoga OR AB yoga) OR (MH “Weight Loss”) OR (TI weight N3 control OR AB weight N3 control) OR (TI “weight loss” OR AB “weight loss”) OR (TI “lose weight” OR AB “lose weight”) OR (MH “Life Style Changes”) OR (MH “Life Style+”) OR (TI lifestyle OR AB lifestyle) OR (TI “life style” OR AB “life style”) OR (TI “health behavior” OR AB “health behavior”) OR (MH “Dietary Supplements+”) OR (MH “Dietary Supplementation”) OR (MH “Medicine, Herbal”) OR (TI non-pharmacolog* OR AB non-pharmacolog*) OR (TI nonpharmacolog* OR AB nonpharmacolog*) OR (TI probiotic* OR AB probiotic*) OR (TI stanols OR AB stanols) OR (TI “oleic acid” OR AB “oleic acid”) OR (MH “Fatty Acids, Omega-3+”) OR (MH “Fatty Acids, Omega-6+”) OR (TI “omega 3” OR AB “omega 3”) OR (TI “omega-3” OR AB “omega-3”) OR (TI “omega 6” OR AB “omega 6”) OR (TI “omega-6” OR AB “omega-6”) OR (TI herbs OR AB herbs) OR (TI herbal OR AB herbal) OR (MH “Fish Oils”) OR (TI “fish oil” OR AB “fish oil”) OR (TI “red yeast rice” OR AB “red yeast rice”) OR (MH “Statins+”) OR (TI statin* OR AB statin*) OR (MH “Antilipemic Agents+”) OR (TI anticholesteremic* OR AB anticholesteremic*) OR (TI hypocholesteremic* OR AB hypocholesteremic*) OR (TI “Hydroxymethylglutaryl-CoA Reductase Inhibitor*” OR AB “Hydroxymethylglutaryl-CoA Reductase Inhibitor*”)) AND ((MH “Aged+”) OR (TI elder* OR AB elder*) OR (TI senior* OR AB senior*) OR (TI “old age” OR AB “old age”) OR (TI “aged adult*” OR AB “aged adult*”) OR (TI “older patient*” OR AB “older patient*”) OR (TI “65 year*” OR AB “65 year*”) OR (TI “70 year*” OR AB “70 year*”) OR (TI “75 year*” OR AB “75 year*”) OR (TI “80 year*” OR AB “80 year*”) OR (TI 65 N4 over OR AB 65 N4 over) OR (TI 70 N4 over OR AB 70 N4 over) OR (TI 75 N4 over OR AB 75 N4 over) OR (TI 80 N4 over OR AB 80 N4 over) OR (TI 65 N4 above OR AB 65 N4 above) OR (TI 70 N4 above OR AB 70 N4 above) OR (TI 75 N4 above OR AB 75 N4 above) OR (TI 80 N4 above OR AB 80 N4 above) OR (TI geriatric OR TI geriatric) OR (TI older W2 adult OR AB older W2 adult) OR (TI “oldest old” OR AB “oldest old”))
Scopus
(TITLE-ABS-KEY (hypercholesterol* OR (high PRE/1 cholesterol) OR {elevated cholesterol} OR {high LDL} OR {elevated HDL} OR {high HDL} OR {elevated HDL} OR {high VLDL} OR {elevated VLDL})) AND (TITLE-ABS-KEY (therapy OR manage OR managed OR manageing OR management OR intervention OR treatment OR prevention OR diet OR dietary OR {oleic acid} OR fasting OR {reduced cholesterol} OR {cholesterol inhibitor} OR {reduced saturated fat} OR {reduced carbohydrates} OR {low carb} OR {low cholesterol} OR {low carbohydrate} OR {low sugar} OR {fat restricted} OR {reduced sugar} OR exercise OR {physical fitness} OR yoga OR {tai ji} OR {tai chi} OR {physical activity} OR {physical activities} OR {physical conditioning} OR walk OR walking OR jog OR jogging OR run OR running OR swim OR swimming OR {weight loss} OR {lose weight} OR {weight control} OR {health behavior} OR {health behaviour} OR {life style} OR lifestyle OR nursing OR non-pharmacolog* OR nonpharmacolog* OR {complementary medicine} OR {alternative medicine} OR probiotic* OR stanol* OR {omega 3} OR {omega 6} OR {fish oil} OR {fish oils} OR herbs OR herbal OR {red yeast rice} OR statin* OR {Hydroxymethylglutaryl-CoA Reductase Inhibitor} OR { Hydroxymethylglutaryl-CoA Reductase Inhibitors} OR anticholesteremic* OR hypocholesteremic*)) AND (TITLE-ABS-KEY (seniors OR {senior citizens} OR {the aged} OR {aged adults} OR {aged patients} OR {65+ years} OR {65 and over} OR {65 and older} OR {over 65} OR {above 65} OR elders OR elderly OR geriatric OR {older adult} OR {older adults} OR {oldest old} OR {old age} OR {older patients} OR {70+ years} OR {70 and over} OR {70 and older} OR {over 70} OR {above 70} OR {75+ years} OR {75 and over} OR {75 and older} OR {over 75} OR {above 75} OR {80+ years} OR {80 and over} OR {80 and older} OR {over 80} OR {above 80} OR {65 years} OR {70 years} OR {75 years} OR {80 years}))
Authors

Dr. Buck is Associate Professor, Dr. Mcghee is Assistant Professor, Mr. Polo is Medical Librarian, and Dr. Zambroski is Associate Professor, College of Nursing, University of South Florida, Tampa, Florida.

The authors have disclosed no potential conflicts of interest, financial or otherwise.

The authors acknowledge the contributions of Dr. Deborah Friedrich during the study selection phase of this project and Dr. Brittany Hay for reviewing the manuscript.

Address correspondence to Harleah G. Buck, PhD, RN, FPCN, FAHA, FAAN, Associate Professor, College of Nursing, University of South Florida, 12901 Bruce B. Downs Boulevard, MDC 22, Tampa, FL 33612; e-mail: hbuck@health.usf.edu.

Received: October 08, 2018
Accepted: January 09, 2019

10.3928/00989134-20190211-04

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