Heart Institute (InCor), University of São Paulo, Medical School Hospital (FMUSP), Sao Paulo, Brazil.
University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Atherosclerosis. 2023 Jan;365:9-14. doi: 10.1016/j.atherosclerosis.2022.12.007. Epub 2022 Dec 23.
Familial hypercholesterolemia (FH) variants are associated with higher atherosclerotic cardiovascular disease risk (ASCVD) even when compared with other forms of severe hypercholesterolemia, especially in young people. Lipid lowering therapies (LLT) may change hypercholesterolemia natural history. This study aimed at evaluating factors associated with occurrence of ASCVD in old severe hypercholesterolemics diagnosed or not with FH and undergoing LLT.
Hypercholesterolemic individuals ≥60 years participating on a genetic cascade screening for FH were divided in 4 groups (2 × 2) according to the presence (variant+) or not (variant-) of FH genetic variants and previous ASCVD (ASCVD+ and ASCVD-). Biomarkers associated with new incident ASCVD events were tested using Cox models. Continuous data shown as medians (%25; %75).
From 4,111 genotyped individuals, 377 (9.1%) were elderly [age 66 (63; 71) years], 28.9% males, 42.7% variant+, 32.1% with previous ASCVD, LLT duration 9 (5; 16) years, and on treatment LDL-cholesterol 144 (109; 200) mg/dL. After 4.8 (7; 3) years of follow up there were 47 incident events (12.4%, 2.7% patient/year). The annualized event rates were 0.8% (95% CI 0.36%; 1.70%), 2.3% (95% CI 1.3%; 4.1%), 5.2% (95% CI 2.8%; 9.7%) and 6.3% (95% CI 4.0%; 10.0%) respectively for groups variant-/ASCVD-, variant+/ASCVD-, variant-/ASCVD+ and, variant+/ASCVD+ (p log rank p < 0.001). Only presence of previous ASCVD was independently associated with incident ASCVD [hazard ratio 3.236 (95%CI 1.497-6.993, p = 0.003)]. No interaction was found for previous ASCVD and variants.
In old severe hypercholesterolemic individuals undergoing long-term LLT previous ASCVD was associated with incident events while FH causing variants were not.
家族性高胆固醇血症（FH）变异与更高的动脉粥样硬化性心血管疾病风险（ASCVD）相关，即使与其他形式的严重高胆固醇血症相比也是如此，尤其是在年轻人中。降脂治疗（LLT）可能会改变高胆固醇血症的自然史。本研究旨在评估在接受 LLT 的诊断或未诊断 FH 的老年严重高胆固醇血症患者中，与 ASCVD 发生相关的因素。
参加 FH 基因级联筛查的高胆固醇血症个体≥60 岁，根据是否存在 FH 基因突变（变异+或变异-）和是否有 ASCVD 史（ASCVD+和 ASCVD-）分为 4 组（2×2）。使用 Cox 模型检测与新发 ASCVD 事件相关的生物标志物。连续数据以中位数（%25；%75）表示。
在 4111 名接受基因检测的个体中，377 名（9.1%）为老年人[年龄 66（63；71）岁]，28.9%为男性，42.7%为变异+，32.1%有 ASCVD 史，LLT 持续时间为 9（5；16）年，治疗 LDL-胆固醇为 144（109；200）mg/dL。随访 4.8（7；3）年后，发生 47 例新发事件（12.4%，2.7%/患者/年）。年化事件发生率分别为 0.8%（95%CI 0.36%；1.70%）、2.3%（95%CI 1.3%；4.1%）、5.2%（95%CI 2.8%；9.7%）和 6.3%（95%CI 4.0%；10.0%）。变异-/ASCVD-、变异+/ASCVD-、变异-/ASCVD+和变异+/ASCVD+组（p log rank p<0.001）。只有既往 ASCVD 存在与新发 ASCVD 独立相关[风险比 3.236（95%CI 1.497-6.993，p=0.003）]。FH 基因突变与既往 ASCVD 之间未发现交互作用。
在接受长期 LLT 的老年严重高胆固醇血症患者中，既往 ASCVD 与新发事件相关，而 FH 引起的变异则不相关。
