This study identified the prevalence of possible cases of FH and associated factors in a representative sample of Brazilian adults. The frequency of FH in adults in Brazil was 1 case in 104 individuals, affecting more women, those aged 45 to 59 years, less educated, with TC ≥ 310 mg/dL, hypertension and diabetes. The presence of FH, regular and very poor/poor health self-assessment, and negatively associated with higher education and black race/color were positively associated. The early identification of individuals with FH is relevant as it can enable early treatment with statins, capable of reducing cardiovascular events in these individuals by up to 76%25.
In this study, the prevalence of possible cases of FH was higher than that estimated in a meta-analysis that found 0.40% (frequency of 1:250)9 and in relation to the Elsa-Brazil study that identified 0.40% (1:263)11. Studies have identified the following prevalence of FH in adults: 0.40% in the United States (1:250)17, 0.30% in China (1:256)10, 0.85% in France (1:120)18 and 0.73% in Denmark (1:137)26, and the frequency in this study approached these last two countries18,26.
The high FH prevalence values found in this study may be influenced by not excluding secondary causes, such as hypothyroidism and nephrotic syndrome1. The exclusion of secondary causes was not possible due to the lack of information in the PNS. Also the absence of genetic testing1, although not mandatory in case of unavailability1,24, may have contributed to the inclusion of other dyslipidemias or metabolic diseases that lead to lipid alterations1,5. It is noteworthy that although we used the adapted Dutch MEDPED criteria, individuals diagnosed with FH by criterion 2 are more likely to have severe hypercholesterolemia by behavioral and non-genetic causes, a possibility that can be corroborated by the higher prevalence of other metabolic alterations in this group when compared by criterion 1. However, considering that early diagnosis and treatment in FH reduce unfavorable clinical outcomes1, it was decided to maintain more sensitive criteria, even losing in specificity.
Studies show that men and women can be equally affected by FH1,27. However, we identified a higher prevalence in women, as in Poland28, Catalonia29 and China10. There is evidence of gender disparities in FH treatment, with the disease having a different weight in women, with implications for treatment adherence30. Women are less likely to use statins and to discontinue therapy, and consequently may not reach recommended LDL-cholesterol levels30. The reasons are related to the challenges faced in the childbearing age regarding the choice of contraceptives and lipid-lowering therapy; discontinuation of treatment with lipid-lowering drugs because they are teratogenic during pregnancy, a phase in which LDL-Cholesterol levels are increased in FH; choice of therapy or restart during breastfeeding; and menopausal care in women with FH, in which LDL-Cholesterol levels are higher compared to men30. Another possible explanation is due to survival bias related to early and fatal manifestations of FH in men11.
Regarding race/color, the result of this investigation diverges from the Elsa-Brazil Study, in which FH affected more browns and blacks11, while a study in the United States identified higher prevalence in whites17. Another study in Brazil with laboratory data from the PNS identified lower prevalence of high LDL-Cholesterol in blacks and browns31. Possible justification is due to the adopted score1,3,5,7, which uses LDL-Cholesterol in its algorithm1,3,5,7. There is no consensus in the literature regarding the genetic factors that allow predicting the highest prevalence of FH in certain ethnic-racial groups32. There is little information about FH in mixed-race populations11, making further research in the country necessary, especially due to miscegenation of Brazilians.
With regard to the relationship of FH with age, a decrease in LDL-Cholesterol levels in FH is expected with advancing years18. However, in this study, the prevalence increased with age, as in studies in French18, Chinese10, Danish26 and Elsa-Brasil20. In the present investigation, as in others that adopted part of the score10,11,17,18,26, the prevalence was lower in young people10,11,26. However, this also occurred in research with more complete scoring algorithms, which included, in addition to LDL-Cholesterol levels and a history of premature CAD and stroke10,11,17,18,26, family history10,11,18,26 and/or genetic test26. Although this phenomenon may be attributable to not using all the score criteria, it implies that FH is underdiagnosed in young people, as it is a genetic condition26. On the other hand, not excluding secondary causes may have increased patients with severe metabolic disorders1, and contributed to overestimating the prevalence of FH at older ages, when secondary causes are more prevalent4.
This study showed a negative association between higher education and the presence of FH. This finding is relevant as adults with FH who have low education are less likely to seek health care, adhere to treatment and advocate for tracking relatives33,34. Patients with FH with low education benefit, therefore, from educational interventions about the disease, constituting important tools for FH control, treatment and tracking among index cases33,34.
Another interesting association was the presence of FH in adults with worse self-rated health. A study with data from PNS showed a strong association between poor health self-assessment and dyslipidemias35. Health self-assessment is a predictor of morbidity and mortality and use of health services35,36. It expresses individuals’ social, psychological and biological dimensions and is related to a greater understanding of the diagnosis, symptoms, decreased functionality and risk of mortality35,36. Possible justifications for these findings can be explained by participants’ perception of the severity and risks36 of FH.
People with diabetes, hypertension and TC ≥ 310 mg/dL had higher prevalence of possible cases of FH, conditions that further increase the risk of CVD in the presence of FH1,37. In people with FH, diabetes increases the risk of CVD by 2.19-fold37 and hypertension confers the 1.4-fold greater risk of CVD37. Thus, it is important to emphasize to individuals with FH the relevance of diagnosis and adoption of treatment for these conditions1,37. Very increased TC values may be indicative of FH and excluding secondary dyslipidemias, these adults should be evaluated for the possibility of the disease1,24.
This study had as limitations: the impossibility of attesting a causal relationship. Associations can reflect lifestyle and treatment. The inexistence of all the score criteria and the impossibility of excluding secondary causes of dyslipidemia, due to the unavailability of information in the PNS base, may have underestimated or overestimated the prevalence. Some results may be subject to survival bias and reverse causality, and should be carefully evaluated. However, in Brazil there is little information about FH6–8. So far, in the only previous population study found, the sample composed of employees of Brazilian public universities11. Although we do not have the exact and robust conditions for defining the disease by the full score, this study allowed us to estimate, for the first time, possible cases of FH and associated factors in a representative sample of Brazilians, approaching the reality of the country and in line with WHO efforts7.
Furthermore, the results imply the importance of introducing an early and systematic FH screening program in the country8. It is worth mentioning that FH diagnosis, in case of unavailability of the genetic test, should be based on LDL-Cholesterol levels and on family tracking of confirmed index cases1,29. Knowing the lipid profile helps to diagnose a greater number of cases1, given that the chances of other carriers from the index case are 50% in first-degree relatives, 25% in second-degree and 12.5% in third-degree38.
Moreover, the identification of high LDL-Cholesterol levels, regardless of FH diagnosis, is relevant, given that these individuals are at increased risk of morbidity and mortality from CVD and should be evaluated for the presence of secondary causes or indication of lipid-lowering treatment, according to the risk cardiovascular39. One fifth of Brazilian adults have high LDL-Cholesterol31, which constituted only in 2019, in Brazil, as the eighth cause of loss of disability-adjusted life years (DALYs), causing 2,363,140 million DALYs (3.62% of the total) and the sixth cause of deaths, causing 99,375 deaths (7.04% of the total)40.