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Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol.
Monday,2024-03-11 14:09 America/Los_Angeles — ecterry
| Title | Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol. |
| Publication Type | Journal Article |
| Year of Publication | 2024 |
| Authors | Zhang, Y, Dron, JS, Bellows, BK, Khera, AV, Liu, J, Balte, PP, Oelsner, EC, Amr, SSamir, Lebo, MS, Nagy, A, Peloso, GM, Natarajan, P, Rotter, JI, Willer, C, Boerwinkle, E, Ballantyne, CM, Lutsey, PL, Fornage, M, Lloyd-Jones, DM, Hou, L, Psaty, BM, Bis, JC, Floyd, JS, Vasan, RS, Heard-Costa, NL, Carson, AP, Hall, ME, Rich, SS, Guo, X, Kazi, DS, de Ferranti, SD, Moran, AE |
| Journal | JAMA Cardiol |
| Date Published | 2024 Jan 31 |
| ISSN | 2380-6591 |
| Abstract | <p><b>IMPORTANCE: </b>Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified.</p><p><b>OBJECTIVE: </b>To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults.</p><p><b>DESIGN, SETTING, AND PARTICIPANTS: </b>A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023.</p><p><b>EXPOSURES: </b>LDL-C, cumulative past LDL-C, FH variant status.</p><p><b>MAIN OUTCOMES AND MEASURES: </b>Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults.</p><p><b>RESULTS: </b>Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant.</p><p><b>CONCLUSIONS AND RELEVANCE: </b>In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.</p> |
| DOI | 10.1001/jamacardio.2023.5366 |
| Alternate Journal | JAMA Cardiol |
| PubMed ID | 38294787 |
| PubMed Central ID | PMC10831623 |
| Grant List | R21 HL153700 / HL / NHLBI NIH HHS / United States R21 HL165405 / HL / NHLBI NIH HHS / United States K23 HL130627 / HL / NHLBI NIH HHS / United States R21 HL129924 / HL / NHLBI NIH HHS / United States R01 HL141823 / HL / NHLBI NIH HHS / United States |
ePub date:
24/01