How Did Breast Cancer Patients Fare during Different Phases of the COVID-19 Pandemic in Norway Compared to Age-Matched Controls?

Little is known about how health-related quality of life (HRQoL) in breast cancer cases differed from that of controls during and after the COVID-19 pandemic. This study used data from an ongoing, nationwide HRQoL survey of 4279 newly diagnosed breast cancer cases and 2911 controls to investigate how breast cancer patients fared during different phases of the pandemic compared to controls. Responders during 2020-2022 were categorized into three COVID-19-related phases: the social restrictions phase, the high infection rate phase, and the post-pandemic phase. Across phases, breast cancer cases had significantly worse scores in most HRQoL domains compared to controls. Apart from slightly more insomnia in the high infection rate phase for both cases and controls, and better social functioning for young cases in the post-COVID-19 phase, the case-control differences in HRQoL remained consistent across phases. When the phases were assessed as one period, young women and those living with children <18 years of age fared the worst among breast cancer cases, while single women fared the worst among controls. In contrast, controls living with children <18 years of age exhibited better HRQoL than controls without children. In summary, women with breast cancer did not appear to fare differently than controls in terms of HRQoL across COVID-19 phases. However, breast cancer cases with young children fared worse in their HRQoL than other breast cancer cases.

Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial.

BACKGROUND: Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. METHODS: N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. RESULTS: SAAR led to a ~ 20% greater weight loss compared to controls (ß 95% CI - 1.14 (- 2.04, - 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. CONCLUSION: Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www. CLINICALTRIALS: gov/study/NCT04701346.

Coping After Breast Cancer: Protocol for a Randomized Controlled Trial of Stress Management eHealth Interventions.

BACKGROUND: One-third or more of breast cancer survivors report stress and other psychological and physical complaints that can negatively impact their quality of life. Psychosocial stress management interventions, shown to mitigate the negative impact of these complaints, can now be delivered as accessible and convenient (for the patient and provider) eHealth interventions. In this randomized controlled trial (RCT), Coping After Breast Cancer (CABC), 2 modified versions of the stress management eHealth intervention program StressProffen were created: one with predominantly cognitive behavioral stress management content (StressProffen-cognitive behavioral therapy intervention [StressProffen-CBI]) and another with predominantly mindfulness-based stress management content (StressProffen-mindfulness-based intervention [StressProffen-MBI]). OBJECTIVE: This study aims to investigate the effects in breast cancer survivors of using StressProffen-CBI and StressProffen-MBI compared with a control group (treatment as usual). METHODS: Women diagnosed with breast cancer (stage I-III, unequivocally human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors) or ductal carcinoma in situ (DCIS) aged 21-69 years who completed the Cancer Registry of Norway-initiated health survey on quality of life are invited to the CABC trial about 7 months after diagnosis. Women who give consent to participate are randomized (1:1:1) to either the StressProffen-CBI, StressProffen-MBI, or control group. Both StressProffen interventions consist of 10 modules of stress management content delivered through text, sound, video, and images. The primary outcome is between-group changes in perceived stress at 6 months, assessed with Cohen 10-item Perceived Stress Scale. The secondary outcomes comprise changes in quality of life, anxiety, depression, fatigue, sleep, neuropathy, coping, mindfulness, and work-related outcomes approximately 1, 2, and 3 years after diagnosis. Long-term effects of the interventions on work participation, comorbidities, relapse or new cancers, and mortality will be assessed using data from national health registries. RESULTS: Recruitment is scheduled from January 2021 to May 2023. The goal is to recruit 430 participants (100 in each group). As of April 14 2023, 428 participants have been enrolled. CONCLUSIONS: The CABC trial is possibly the largest ongoing psychosocial eHealth RCT in patients with breast cancer. If 1 or both interventions prove to be effective in reducing stress and improving psychosocial and physical complains, the StressProffen eHealth interventions could be beneficial, inexpensive, and easily implementable tools for breast cancer survivors when coping with late effects after cancer and cancer treatments. TRIAL REGISTRATION: Clinicaltrials.gov NCT04480203; https://clinicaltrials.gov/ct2/show/NCT04480203. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47195.

The association of fasting plasma thiol fractions with body fat compartments, biomarker profile, and adipose tissue gene expression.

People with high plasma total cysteine (tCys) have higher fat mass and higher concentrations of the atherogenic apolipoprotein B (apoB). The disulfide form, cystine, enhanced human adipogenesis and correlated with total fat mass in a Middle-Eastern cohort. In 35 European adults with overweight (88.6% women) and with dual-X-ray absorptiometry measurements of regional fat, we investigated how cystine compared to other free disulfides in their association with total regional adiposity, plasma lipid and glucose biomarkers, and adipose tissue lipid enzyme mRNA (n = 19). Most total plasma homocysteine (tHcy) (78%) was protein-bound; 63% of total glutathione (tGSH) was reduced. tCys was 49% protein-bound, 30% mixed-disulfide, 15% cystine, and 6% reduced. Controlling for age and lean mass, cystine and total free cysteine were the fractions most strongly associated with android and total fat: 1% higher cystine predicted 1.97% higher android fat mass (95% CI 0.64, 3.31) and 1.25% (0.65, 2.98) higher total fat mass (both p = 0.005). A positive association between tCys and apoB (ß: 0.64%; 95% CI 0.17, 1.12%, p = 0.009) was apparently driven by free cysteine and cystine; cystine was also inversely associated with the HDL-associated apolipoprotein A1 (ß: -0.57%; 95% CI -0.96, -0.17%, p = 0.007). No independent positive associations with adiposity were noted for tGSH or tHcy fractions. Plasma cystine correlated with CPT1a mRNA (Spearman's r = 0.68, p = 0.001). In conclusion, plasma cystine-but not homocysteine or glutathione disulfides-is associated with android adiposity and an atherogenic plasma apolipoprotein profile. The role of cystine in human adiposity and cardiometabolic risk deserves investigation. ClinicalTrials.gov identifiers: NCT02647970 and NCT03629392.

Risk of stroke in genetically verified familial hypercholesterolemia: A prospective matched cohort study.

BACKGROUND AND AIMS: Individuals with familial hypercholesterolemia (FH), causing severely elevated LDL-C, are expected to have a higher risk of ischemic stroke. The risk of hemorrhagic stroke and impact of statin use are, however, not known. We aimed to investigate the risk of incident total, ischemic and hemorrhagic stroke in individuals with FH compared to controls, and to explore the association between cumulative statin use and risk of total stroke in FH. METHODS: This prospective cohort study consists of 4186 individuals with genetically verified FH and 82 180 age and sex matched controls followed from 2008 to 2018 for incident stroke. Daily defined doses (DDD) described cumulative statin exposure: 0-5000 DDD ("low"), 5000-10,000 DDD ("intermediate"), and >10 000 DDD ("high"). Results were presented as hazard ratio (95% CI) derived from Cox proportional hazards models. RESULTS: Individuals with FH did not have a higher risk of total stroke (1.16 (0.95-1.43) nor ischemic stroke (1.11 (0.88-1.38). Excess risk of hemorrhagic stroke was observed (1.63 (1.07, 2.48) but attenuated after adjusting for antithrombotic medication (1.25 (0.81, 1.93). Among individuals with FH, there was no association between statin use and total stroke for intermediate vs. low DDD [0.69 (0.32, 1.48)] or for high vs. low DDD [0.83 (0.41, 1.67)]. CONCLUSIONS: No significant excess risk of incident total and ischemic stroke in FH, and no difference in total stroke risk among the FH population with low, intermediate, and high statin exposure were observed. The observed relationship between FH and hemorrhagic stroke was no longer significant after adjusting for use of anti-thrombotic medication.

Association of Familial Hypercholesterolemia and Statin Use With Risk of Dementia in Norway.

Importance: Hypercholesterolemia, which is a cardiovascular risk factor, may also be associated with dementia risk. The benefit of statin treatment on dementia risk is controversial. Objective: To determine whether individuals with familial hypercholesterolemia (FH), who have been exposed to lifelong hypercholesterolemia, have an excess risk of dementia and whether statin use is associated with dementia risk. Design, Setting, and Participants: This was a prospective cohort study performed from 2008 to 2018 in Norway. Statistical analysis was performed from January 2021 to February 2022. This study included individuals with genetically verified FH and age-matched and sex-matched controls obtained from the general Norwegian population. Exposures: Dementia was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F00-03 and G30. Main Outcomes and Measures: Incident cases of total dementia, vascular dementia, Alzheimer disease-dementia in Alzheimer disease, and data on lipid-lowering medication were obtained from the Norwegian Patient Registry, Cause of Death Registry, and the Norwegian Prescription Database. Hazard ratios (HRs) for risk of dementia for individuals with FH vs matched controls were calculated using Cox regression. The cumulative sum of defined daily doses (DDDs) of statins prescribed during study follow-up was calculated for individuals with FH and was analyzed as a time-varying covariate with 3 levels: 1 to 4999 DDDs, 5000 to 10 000 DDDs, and more than 10 000 DDDs. Results: Among the 3520 individuals with FH (1863 women [52.9%]; mean [SD] age at the start of follow-up, 51.8 [11.5] years) and the 69 713 controls (36 958 women [53.0%]; mean [SD] age at the start of follow-up, 51.7 [11.5] years), 62 patients with FH (39 women [62.9%]) and 1294 controls (801 women [61.9%]) had developed dementia over the course of 10 years of follow-up. Most dementia cases occurred among individuals aged 70 years and older (39 patients with FH [62.9%] and 870 patients [67.2%] in the control group). We found no excess risk of dementia in patients with FH vs matched controls (HR for total dementia, 0.9; 95% CI, 0.7-1.2). There was no association between cumulative DDDs of statins and total dementia in patients with FH with HRs of 1.2 (95% CI, 0.4-3.8) for cumulative DDDs of 5000 to 10 000 and 1.9 (95% CI, 0.7-5.0) for cumulative DDDs greater than 10 000. Conclusions and Relevance: These findings suggest that individuals with FH have no excess risk of dementia compared with age-matched and sex-matched controls and that there is no association between use of statins and risk of dementia in patients with FH.

Simple Nutrient-Based Rules vs. a Nutritionally Rich Plant-Centered Diet in Prediction of Future Coronary Heart Disease and Stroke: Prospective Observational Study in the US.

To better understand nutrition paradigm shift from nutrients to foods and dietary patterns, we compared associations of a nutrient-based blood cholesterol-lowering diet vs. a food-based plant-centered diet with risk of coronary heart disease (CHD) and stroke. Participants were 4701 adults aged 18-30 years and free of cardiovascular disease at baseline, followed for clinical events from 1985 and 86 to 2018. A plant-centered diet was represented by higher A Priori Diet Quality Score (APDQS). A blood cholesterol-lowering diet was represented by lower Keys Score. Proportional hazards regression was used to calculate hazard ratios (HR). Higher APDQS showed a nutrient-dense composition that is low in saturated fat but high in fiber, vitamins and minerals. Keys Score and APDQS changes were each inversely associated with concurrent plasma low-density lipoprotein cholesterol (LDL-C) change. Over follow-up, 116 CHD and 80 stroke events occurred. LDL-C predicted CHD, but not stroke. APDQS, but not Keys Score, predicted lower risk of CHD and of stroke. Adjusted HRs (95% CIs) for each 1-SD higher APDQS were 0.73 (0.55-0.96) for CHD and 0.70 (0.50-0.99) for stroke. Neither low dietary fat nor low dietary carbohydrate predicted these events. Our findings support the ongoing shift in diet messages for cardiovascular prevention.

The homeoviscous adaptation to dietary lipids (HADL) model explains controversies over saturated fat, cholesterol, and cardiovascular disease risk.

SFAs play the leading role in 1 of the greatest controversies in nutrition science. Relative to PUFAs, SFAs generally increase circulating concentrations of LDL cholesterol, a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, the purpose of regulatory mechanisms that control the diet-induced lipoprotein cholesterol dynamics is rarely discussed in the context of human adaptive biology. We argue that better mechanistic explanations can help resolve lingering controversies, with the potential to redefine aspects of research, clinical practice, dietary advice, public health management, and food policy. In this paper we propose a novel model, the homeoviscous adaptation to dietary lipids (HADL) model, which explains changes in lipoprotein cholesterol as adaptive homeostatic adjustments that serve to maintain cell membrane fluidity and hence optimal cell function. Due to the highly variable intake of fatty acids in humans and other omnivore species, we propose that circulating lipoproteins serve as a buffer to enable the rapid redistribution of cholesterol molecules between specific cells and tissues that is necessary with changes in dietary fatty acid supply. Hence, circulating levels of LDL cholesterol may change for nonpathological reasons. Accordingly, an SFA-induced raise in LDL cholesterol in healthy individuals could represent a normal rather than a pathologic response. These regulatory mechanisms may become disrupted secondarily to pathogenic processes in association with insulin resistance and the presence of other ASCVD risk factors, as supported by evidence showing diverging lipoprotein responses in healthy individuals as opposed to those with metabolic disorders such as insulin resistance and obesity. Corresponding with the model, we suggest alternative contributing factors to the association between elevated LDL cholesterol concentrations and ASCVD, involving dietary factors beyond SFAs, such as an increased endotoxin load from diet-gut microbiome interactions and subsequent chronic low-grade inflammation that interferes with fine-tuned signaling pathways.

2.5-fold increased risk of recurrent acute myocardial infarction with familial hypercholesterolemia.

BACKGROUND AND AIMS: A first-time acute myocardial infarction (AMI) is a severe diagnosis that leads to initiation or intensification of lipid-lowering medication to prevent recurrent events. Individuals with familial hypercholesterolemia (FH) already use high-intensity lipid-lowering medication at the time of an incident AMI due to their diagnosis. Hence, we hypothesized that compared with matched non-FH controls, individuals with genetically verified FH have increased mortality and risk of recurrent AMI after their first event. METHODS: The study population comprised 4871 persons with genetically verified FH, and 96,251 age and sex matched controls randomly selected from the Norwegian population. Data were obtained from the Cardiovascular Disease in Norway Project, the Norwegian Patient Registry and the Norwegian Cause of Death Registry. Incidence of AMI, all-cause mortality and recurrent AMI after incident AMI were analyzed for the period 2001-2017. Incidence and mortality were compared using hazard ratios (HR) from Cox regression. Risk of recurrent AMI was compared using sub-hazard ratios (SHR) from competing risk regression with death as a competing event. RESULTS: We identified 232 individuals with FH and 2118 controls with an incident AMI [HR 2.10 (95% CI 1.83-2.41)]. Among survivors ≥29 days after the incident AMI, both mortality [HR = 1.45 (95% CI: 1.07-1.95)] and recurrent AMI [SHR = 2.53 (95% CI: 1.88-3.41)] were significantly increased among individuals with FH compared with non-FH controls. CONCLUSIONS: Individuals with FH have increased mortality and increased risk of recurrent AMI after the first AMI event compared with controls. These findings call for intensive follow-up of individuals with FH following an AMI.

Genetic testing is essential for initiating statin therapy in children with familial hypercholesterolemia: Examples from Scandinavia.

BACKGROUND AND AIMS: In familial hypercholesterolemia (FH), statin treatment should be considered from 8 to 10 years of age, but the prevalence of statin use among children is not known. METHODS: Statin use (2008-2018) among children aged 10-14 and 15-19 years was obtained from the national prescription databases in Norway, Sweden and Denmark. We assumed that all statin users in these age groups had FH, and that the estimated prevalence of FH is 1 in 250 inhabitants. Changes in prevalence rates of statin use between 2008 and 2018 by country, age and sex were estimated using the Joinpoint Regression Program version 4.8.0.1. Differences in prevalence rate ratio each year between countries were analyzed using Poisson regression. RESULTS: Among children aged 10-14 years, there was a significant increase in statin use in Norway and Denmark between 2008 and 2018, while in Sweden an increase was only seen after 2014. Among children aged 15-19 years, an increase in statin use was only observed in Norway and Sweden between 2008 and 2018. Statin use was significantly more prevalent in Norway than in Sweden and Denmark each year, and in 2018 the proportion of children using statins was 4-5 times (10-14 years) and 3 times (15-19 years) higher in Norway compared with Sweden and Denmark. In 2018 in Norway, 19% and 35% of children aged 10-14 years and 15-19 years estimated to have FH used statins respectively; corresponding percentages in Sweden were 4.5% and 10%, and in Denmark 3% and 12%. In Norway, the increase in statin use between 2008 and 2018 roughly corresponded to the increase in children with genetically verified FH. CONCLUSIONS: Between 2008 and 2018, statin use increased in children aged 10-19 years in Norway, Sweden and Denmark, but with large differences between the countries; statin use was 3-5 times more prevalent in Norway than in Sweden and Denmark, which may be due to a more widespread use of genetic testing for FH in Norway.

Fatty acid profile and estimated desaturase activities in whole blood are associated with metabolic health.

BACKGROUND: The aim was to investigate if fatty acid profile and estimated desaturase activities; stearoyl CoA-desaturase (SCD), delta-5-desaturase and delta-6-desaturase (D5D; D6D), differ between individuals with metabolically healthy (MH) and unhealthy (MU) phenotypes. We also explored these associations according to BMI categories. METHODS: Men and women at moderately elevated risk of cardiovascular disease were included in this cross-sectional study (n = 321). If subjects met ≥4 out of 5 criteria (elevated triglycerides, total and LDL-cholesterol, HbA1c and low HDL-cholesterol), they were classified as MU (n = 52). If levels were within reference ranges for ≥3 of the same criteria, subjects were classified as MH (n = 150). Utilizing the entire population, a score ranging from 0 to 5 denoting the number of MU criteria met was computed. Estimated desaturase activities were calculated as product-to-precursor ratio of fatty acids in whole blood (SCD16 [16:1n7/16:0], SCD18 [18:1n9/18:0], D5D [18:3n6/18:2n6], D6D [20:4n6/20:3n6]). RESULTS: Individuals with MH had lower estimated SCD16 and SCD18 activities, whereas estimated D6D activity was higher compared to MU. Similar, SCD16 and SCD18 increased, whereas D6D decreased with increasing criteria of MU. Trends were similar across BMI categories. CONCLUSIONS: This study supports the notion of estimated desaturase activities as possible novel biomarkers of metabolic health irrespectively of BMI.

Evaluating the use of the heart age tool in community pharmacies: a 4-week cluster-randomized controlled trial.

BACKGROUND: Joint British Societies have developed a tool that utilizes information on cardiovascular disease (CVD) risk factors to estimate an individual's 'heart age'. We studied if using heart age as an add-on to conventional risk communication could enhance the motivation for adapting to a healthier lifestyle resulting in improved whole-blood cholesterol and omega-3 status after 4 weeks. METHODS: A total of 48 community pharmacies were cluster-randomized to use heart age+conventional risk communication (intervention) or only conventional risk communication (control) in 378 subjects after CVD risk-factor assessment. Dried blood spots were obtained with a 4-week interval to assay whole-blood cholesterol and omega-3 fatty acids. We also explored pharmacy-staff's (n=27) perceived utility of the heart age tool. RESULTS: Subjects in the intervention pharmacies (n=137) had mean heart age 64 years and chorological age 60 years. In these, cholesterol decreased by median (interquartile range) -0.10 (-0.40, 0.35) mmol/l. Cholesterol decreased by -0.20 (-0.70, 0.30) mmol/l (P difference =0.24) in subjects in the control pharmacies (n=120) with mean chronological age 60 years. We observed increased concentrations of omega-3 fatty acids after 4 weeks, non-differentially between groups. Pharmacy-staff (n=27) agreed that heart age was a good way to communicate CVD risk, and most (n=25) agreed that it appeared to motivate individuals to reduce elevated CVD risk factors. CONCLUSIONS: The heart age tool was considered a convenient and motivating communication tool by pharmacy-staff. Nevertheless, communicating CVD risk as heart age was not more effective than conventional risk communication alone in reducing whole-blood cholesterol levels and improving omega-3 status.

Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study.

BACKGROUND: Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the translational potential in humans, we evaluated the effects of dietary methionine and cysteine restriction on cardiometabolic risk factors, plasma and urinary amino acid profile, serum fibroblast growth factor 21 (FGF21), and subcutaneous adipose tissue gene expression in women with overweight and obesity in a double-blind randomized controlled pilot study. METHODS: Twenty women with overweight or obesity were allocated to a diet low (Met/Cys-low, n = 7), medium (Met/Cys-medium, n = 7) or high (Met/Cys-high, n = 6) in methionine and cysteine for 7 days. The diets differed only by methionine and cysteine content. Blood and urine were collected at day 0, 1, 3 and 7 and subcutaneous adipose tissue biopsies were taken at day 0 and 7. RESULTS: Plasma methionine and cystathionine and urinary total cysteine decreased, whereas FGF21 increased in the Met/Cys-low vs. Met/Cys-high group. The Met/Cys-low group had increased mRNA expression of lipogenic genes in adipose tissue including DGAT1. When we excluded one participant with high fasting insulin at baseline, the Met/Cys-low group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys-high group. The participants reported satisfactory compliance and that the diets were moderately easy to follow. CONCLUSIONS: Our data suggest that dietary methionine and cysteine restriction may have beneficial effects on circulating biomarkers, including FGF21, and influence subcutaneous adipose tissue gene expression. These results will aid in the design and implementation of future large-scale dietary interventions with methionine and cysteine restriction. Trial registration ClinicalTrials.gov Identifier: NCT03629392, registration date: 14/08/2018 https://clinicaltrials.gov/ct2/show/NCT03629392.

Lower risk of smoking-related cancer in individuals with familial hypercholesterolemia compared with controls: a prospective matched cohort study.

According to guidelines, individuals with familial hypercholesterolemia (FH) shall receive lifestyle intervention and intensive lipid-lowering treatment from early in life to reduce the risk of coronary heart disease. Our aim was to study if treatment of FH also could affect risk of lifestyle-related cancer. We presented cumulative incidence of total cancer and lifestyle-related cancer sites in individuals with genetically verified FH (n = 5531) compared with age and sex matched controls (n = 108354). Individuals with FH had 20% lower risk of smoking-related cancer compared with the control population [HR 0.80 (95% CI, 0.65-0.98)], in particular men with FH at 40-69 years at age of diagnosis with HR 0.69 (95% CI, 0.49-0.97). The FH population and controls had similar rates of total cancer [HR 0.97 (95% CI, 0.86-1.09)], cancer related to poor diet [HR 0.82 (95% CI, 0.59-1.15)], cancer related to physical inactivity [HR 0.93 (95% CI, 0.73-1.18)], alcohol-related cancer [HR 0.98 (95% CI, 0.80-1.22)] and cancer related to obesity [HR 1.03 (95% CI, 0.89-1.21)]. In summary, we found reduced risk of smoking-related cancer in individuals with FH, most likely due to a lower prevalence of smoking. Implications of these findings can be increased motivation and thus compliance to treatment of hypercholesterolemia.