RESUMO
BACKGROUND: Clinically diagnosed familial hypercholesterolemia (FH) may require a genetic test (GT) to confirm diagnosis. GT availability/accessibility is resource-dependent and usually restricted to specialized clinics. While GT has a diagnostic value, it has not yet defined its impact on long-term management and prognosis of FH. OBJECTIVE: The aim was to identify the clinical characteristics associated with the request for a GT in suspected heterozygous FH. METHODS: Retrospective study including adult patients with clinically suspected to be FH. Positive GT (GT+) was defined as having a pathogenic/likely pathogenic variant. Patients were stratified based on whether they had a genetic study conducted, and among those with a genetic study, according to those who did or did not have a GT+. RESULTS: From 4854 patients included, 3090 were performed a GT (GT+: 2113). Median follow-up: 6.2 years. A younger age, FH-related physical signs, premature coronary disease, higher low-density lipoprotein cholesterol (LDLc) and lower body mass index and triglycerides, associated higher odds of being conducted a genetic study. These patients had higher baseline LDLc (252 mg/dL vs. 211 mg/dL among clinically diagnosed patients) and experienced larger reductions over the follow-up (157.7 mg/dL vs. 113.5 mg/dL, respectively). A similar pattern was observed among patients with GT+ (vs. negative GT). LDLc target attainment was low but increased to 66-95% when a triple combination with statin/ezetimibe/proprotein convertase subtilisin kexin type 9-inhibitor was used. Cardiovascular events occurred in 3.2% and 3.1% of patients who conducted/not conducted a genetic study. Patients conducted a genetic analysis and those with GT+ tended to present the events earlier. CONCLUSIONS: Genetic study, vs. having a clinical-only diagnosis, impacts the management of FH. Cardiovascular prognosis was similar in both groups, perhaps as a result of the more intensive management of patients with a genetic study.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Adulto , Humanos , Estudos Retrospectivos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ezetimiba/uso terapêuticoRESUMO
Fasting and postprandial triglyceride concentrations largely depend on dietary and lifestyle factors. Alcohol intake is associated with triglycerides, but the effect of alcohol on diurnal triglyceridemia in a free living situation is unknown. During three days, 139 men (range: 18-80 years) measured their own capillary triglyceride (cTG) concentrations daily on six fixed time-points before and after meals, and the total daily alcohol intake was recorded. The impact of daily alcohol intake (none; low, <10 g/day; moderate, 10-30 g/day; high, >30 g/day) on diurnal triglyceridemia was analyzed by the incremental area under the cTG curve (∆cTG-AUC) reflecting the mean of the six different time-points. Fasting cTG were similar between the alcohol groups, but a trend of increased cTG was observed in men with moderate and high alcohol intake after dinner and at bedtime (p for trend <0.001) which persisted after adjustment for age, smoking and body mass index. The ∆cTG-AUC was significantly lower in males with low alcohol intake (3.0 ± 1.9 mmol·h/L) (n = 27) compared to males with no (7.0 ± 1.8 mmol·h/L) (n = 34), moderate (6.5 ± 1.8 mmol·h/L) (n = 54) or high alcohol intake (7.2 ± 2.2 mmol·h/L) (n = 24), when adjusted for age, smoking and body mass index (adjusted p value < 0.05). In males, low alcohol intake was associated with decreased diurnal triglyceridemia, whereas moderate and high alcohol intake was associated with increased triglycerides after dinner and at bed time.