Eur J Public Health. 2014 Apr;24(2):221-5.

Quality of life in a cohort of familial hypercholesterolemia patients from the south of Europe.


Mata N1, Alonso R2, Banegas JR3, Zambón D4, Brea A5, Mata P2

1 Department of Epidemiology, Madrid Health Authority, Spain

2 Lipid Clinic, Internal Medicine Department IIS-Fundación Jimenez Diaz, Madrid, Spain

3 Department of Preventive Medicine and Public Health. Universidad Autónoma de Madrid/IdiPaz, Madrid, Spain

4 Lipid Clinic, Instituto de Investigaciones Biomedicas August Pi Sunyer. Hospital Clinic, Barcelona, Spain

5 Lipid Clinic, Internal Medicine Department, Hospital San Pedro, Logronño, Spain



Objectives: This study describes health-related quality of life (HRQL) in a large sample of molecularly defined familial hypercholesterolemia (FH) patients compared with unaffected relatives.

Study design and setting: Cross-sectional study of cases recruited in the Spanish FH cohort study. A total of 1947 subjects ≥ 18 years were include (1321 FH and 626 unaffected relatives). HRQL was assessed by 12-Item Short-Form Health Survey questionnaire. Main outcomes were as follows: Self-perceived health, Physical summary component, Mental summary component and their independent covariates.

Results: Mean age was 45.3 years in FH subjects and 40.4 years in control subjects (p < 0.001). Cardiovascular disease (CVD) was present in 14.1% of FH patients and in 3.2% of control subjects (p < 0.001). Frequency of optimal self-perceived health, mean physical summary component and mental summary component of FH patients (81.5%, 52.1 and 51.1, respectively), were similar to those of control subjects (83.1%, 53.1 and 51.1, respectively). Factors independently associated with a worse HRQL in FH patients were as follows: CVD, female gender, older age, depression, obesity, lower educational level, lower physical activity and xanthomas.

Conclusions: HRQL of FH patients was similar to control subjects, despite their higher burden of premature CVD. The most important factors with a negative impact in quality of life in FH are CVD, female gender and older age.

PMID: 23264649



Familial hypercholesterolemia (FH) is the most common monogenic disorder with an estimated prevalence of one every 400–500 persons. It is caused mainly by mutations in the low-density lipoprotein receptor, resulting in an increased level of plasma low-density lipoprotein cholesterol (LDL-c), leading to premature atherosclerotic cardiovascular disease (CVD). Life expectancy of FH patients is shortened by 20–30 years compared with the general population.1 However, current evidence suggests that treatment with statins effectively reduces the coronary risk in FH patients.2

Few studies have assessed quality of life in patients with FH, and they have shown that there is little or no significant difference in health-related quality of life (HRQL) in FH subjects compared with the general population.3 This is the first study performed in a large sample of well molecularly defined FH population.

Health-related quality of life (HRQL) represents the individual perception of the impact of health problems on different spheres of life, including physical, mental and social aspects4. There is evidence that HRQL is an indicator of disease severity: specifically, a lower HRQL is associated with greater mortality among older adults with coronary disease and other chronic conditions5. HRQL is also a good predictor of health services use6. In older adults from the general population, HRQL is also a good indicator of health status with prognostic significance, in fact it has been proved that a lower HRQL predicts long-term mortality7.

The main objective of this study is to describe HRQL in a large cohort of Spanish patients with genetic diagnosis of FH and to compare it with their unaffected relatives. Secondary objectives are to analyze HRQL according to socio-demographic and clinical characteristics including history of CVD and CV risk factors in both groups and to determine the factors associated with HRQL among FH patients.

The study design is a cross-sectional analysis of cases recruited in the Spanish FH cohort study8. Inclusion criteria were cases ≥18 years old with genetic diagnosis of FH and their unaffected relatives as a control group.

The questionnaires used in the study to assess HRQL was the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) validated in Spain9,10.These items can be transformed into two summary scores, representing physical and mental summary measures: the Physical Summary Component (PSC) and the Mental Summary Component (MSC). To facilitate the interpretation of these scores, they are standardized to the values of the population norms so that 50 (standard deviation 10) is the average value for general population. Values greater or less than 50 should be interpreted as best or worst, respectively, than the reference population. Other outcome of HRQL used for analysis was self-perceived health. It is obtained by the first item of SF-12 questionnaire (‘In general would you say your health is excellent, very good, good, fair or poor?’), which was categorized as ‘optimal’ and ‘suboptimal’.

Physical activity (PA) was assessed by the short form of the International Physical Activity Questionnaire11 which provides separate scores on three types of activity: walking, moderate and vigorous-intensity activity. Categorical (low, moderate and high PA level) and continuous indicators (Metabolic Equivalent/week or MET-hours/week) of PA can be obtained. The continuous indicator of total PA MET-hours/week is the sum of walking and moderate-to-vigorous MET hours/week scores. MET score was obtained for each type of activity using the Ainsworth et al. compendium12.


Figure 1

Figure 1. Frequency of Cardiovascular disease in FH patients compared to control subjects.


The results of our study are as follow: a total of 1947 subjects (aged 18–80 years) were included in the analysis: 1321 FH patients (67.8%) and 626 unaffected relatives (32.1%) from 402 families. There were no differences in gender or educational level among FH and control subjects. Mean age was 45.3 years in FH subjects and 40.4 years in control subjects (p<0.001). History of CVD was present in 14.1% of FH patients compared with 3.2% in control subjects (p < 0.001), almost 5 times more prevalence of CVD in FH compared to controls (figure 1). Prevalence of xanthomas among FH subjects was 14.7%. 

The prevalence of current smokers was significantly higher in control subjects compared with FH patients (34.7% vs. 28.0%, p<0.001). With respect to Physical activity (PA), 79.6% of FH patients reported moderate-vigorous level of PA, compared with 72.2% of control subjects (p<0.001). There were no significant differences in prevalence of type 2 diabetes, hypertension, depression, cancer and overweight/obesity between both groups.

The percentage of optimal self-perceived health and mean PSC and MSC was similar in FH patients (81.5%, 52.1 and 51.1, respectively) and control subjects (83.1%, 53.1, 51.1, respectively) (Figure 2)


 Figure 2

Figure 2. HRQL of FH patients compared to controls


Two regression statistical models (a binary logistic model and a multiple lineal regression model) were performed to determine the variables associated with a worse HRQL (suboptimal health, PSC and MSC) after adjusting for age, sex, educational level, CVD, Diabetes type II, Hypertension, BMI, Tobacco consumption, Physical activity, depression, cancer, xanthomas and years of lipid lowering therapy. The factors independently associated with a worse HRQL in FH patients were as follows: CVD, female gender, older age, depression, obesity, lower educational level, lower physical activity and xanthomas.

We can conclude that the present study shows that HRQL in Spanish patients with genetic diagnosis of FH was similar to that of their unaffected relatives, despite their higher burden of premature CVD. The most important factors independently associated with a worse HRQL in patients with FH were CVD, female gender and older age. Previous studies from the north of Europe showed no differences in HRQL between FH patients and the general population3,13 which is in line with the main result of this study. This could be explained in part by the asymptomatic course of the disorder in patients with long-term Lipid lowering therapy and furthermore because this FH population have a healthier lifestyle with a lower prevalence of smokers and a higher level of PA when compared with control subjects.

Importance of the study: these findings show that early detection of subjects with FH is essential in order to implement early intervention strategies based on lifestyle changes and the beginning of an effective lipid-lowering therapy that will probably prevent the further development of premature CVD and therefore improve quality of life in this high risk population.


Figure 3. Key points

Figure 3. Key points of the study



  1. World Health Organization. Human Genetic Program. Familial Hypercholesterolemia. (WHO/HGN/FH/CONS/98.7, Paris 1997).
  2. Versmissen J, Oosterveer DM, Yazdanpanah M, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ 2008;337:a2423.
  3. Hyttinen L, Kekäläinen P, Vuorio AF, Sintonen H, Strandberg TE. Health-related quality of life in elderly patients with familial hypercholesterolemia. Int J Technol Assess Health Care. 2008;24:228-34.
  4. Testa, M. A., & Simonson, D. C. Assesment of qualityof-life outcomes. New England Journal of Medicine 1996; 334(13),835–840.
  5. Rumsfeld, J. S., MaWhinney, S., McCarthy, M., Jr., Shroyer, A. L.,VillaNueva, C. B., O’Brien, M., et al. Health-related quality of life as a predictor of mortality following coronary artery bypass graft surgery. Participants of the department of veterans affairs cooperative study group on processes, structures, and outcomes of care in cardiac surgery. JAMA 1999; 281(14): 1298–1303.
  6. Fan, V. S., Au, D. H., McDonell, M. B., & Fihn, S. D.. Intraindividual change in SF-36 in ambulatory clinic primary care patients predicted mortality and hospitalizations. Journal of Clinical Epidemiology 2004; 57(3):277–283.
  7. Kaplan, M. S., Berthelot, J. M., Feeny, D., McFarland, B. H.,Khan, S., & Orpana, H. The predictive validity of healthrelated quality of life measures: Mortality in a longitudinal population-based study. Quality of Life Research 2007; 16(9): 1539–1546.
  8. Mata N, Alonso R, Badimon L, et al. Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART). Lipid Health Dis 2011;10:94.
  9. Ware JE Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996;34:220–33.
  10. Gandek B, Ware JE, Aaronson NK, et al. Cross-validation of item selection and scoring for the SF-12 Health Survey in nine countries: results from the IQOLA Project. International Quality of Life Assessment. J Clin Epidemiol 1998;51:1171-8.
  11. Rutten A, Ziemainz H, Schena F, et al. Using different physical activity measurements in eight European countries. Results of the European physical activity surveillance system (EUPASS) time series survey. Public Health Nutr 2003;6:371–6.
  12. Ainsworth BE, Haskell WL, Whitt MC, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000;32: S498–504.
  13. Hollman G, Gullberg M, Ek AC, et al. Quality of life in patients with familial hypercholesterolaemia. J Intern Med 2002;251:331–7.



Acknowledgements: This study has been supported by Spanish Familial Hypercholesterolemia Foundation and grant 08-2008 from National Center for Cardiovascular Research (CNIC), Spain.



Dr. Nelva Mata (MD, Ph.D.)

Department of Epidemiology

Madrid Health Authority,

C/Oceano Pacífico 3, 28821Coslada (Madrid)





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