LM is a 26-year-old man with a medical history significant for ulcerative colitis, diagnosed at age 21. Despite treatment with oral and suppository mesalamine and hydrocortisone enemas, he was unable to remain in remission for longer than 8 weeks. At 23, he experimentally adopted a Mediterranean-style ketogenic diet [with an emphasis on intake of fatty seafood, extra virgin olive oil, and low-carbohydrate fibrous fruits and vegetables ] and entered a 6-month period of remission, following which he elected to discontinue all medications and has largely remained in remission. Since adopting a ketogenic diet two and a half years ago, LM has only experienced colitis flares on three occasions: twice when trying to reintroduce carbohydrates in the form of honey, fruit, and/or starchy vegetables, and once following acute mold exposure.
As previously reported, in the first 6 months following carbohydrate restriction, LM's LDL-C increased from 95 mg/dl to 321 mg/dl, along with low TG and an increase in HDL-C from 48 to 109 mg/dl. This change occurred despite LM's self-reported prioritization of foods rich in unsaturated fats, restricted intake of saturated fat-rich foods, such as red meat and dairy, and moderate fiber intake of ~30 g/day. Of note, LM subsequently reduced intake of fiber in order to manage constipation, and current intake is ~15 g/day.
When statin therapy was recommended to LM upon first presentation with hypercholesterolemia, he declined. While he expressed concern about his LDL-C levels, he also conveyed reluctance about consenting to potentially lifelong pharmacotherapy without first attempting to address his hypercholesterolemia with diet and lifestyle change. LM attempted on two occasions to reintroduce carbohydrates to lower his LDL-C. On both occasions, he experienced near-immediate gastrointestinal discomfort and blood in the stool within a week. Although he initially declined statins, he consented to trial ezetimibe but experienced gastrointestinal discomfort and discontinued treatment.
To further investigate potential contributing dietary factors to his hypercholesterolemia within the context of his ketogenic diet, in August 2020, LM began measuring his dietary intake using a gram food scale and by keeping fastidious dietary records in the 7 days prior to scheduled lipid testing. Nutritional information extracted from these records, using data exported from the USDA Food Central database along with brand-specific nutrition information, is provided with photographs of representative meals in  Supplemental Information .
Lipid and metabolic panels over the years have been notable for elevated LDL-C-related markers, LDLp and apoB, and elevated Lp(a) ranging from 109 to 168 mg/dl. Despite his low LDL-C while consuming a mixed diet (95 mg/dl), Lp(a) was elevated in LM prior to starting a ketogenic diet and is also elevated in LM's father, who has a history of coronary artery disease manifesting in 99% left anterior descending stenosis at age 44, although the father presented with a profile in strong contrast to his son: unremarkable LDL-C (70-92 mg/dl), atherogenic dyslipidemia (HDL-C 33-39 mg/dl, TG 199-294 mg/dl, with a preponderance of sdLDL), and history of obesity. (NB: Subsequent to his event, the father adopted a CRD and has lost 50 lbs and reversed metabolic syndrome, while maintaining LDL-C <100 mg/dl on atorvastatin and ezetimibe). LM exhibits normal thyroid and testosterone, HbA1c (4.8-5.0%), and fasting insulin (<3 muIU/ml), low hsCRP (<1.0 mg/L), Pattern A phenotype, and an extremely low TG/HDL-C ratio (~0.3) characteristic of the LMHR phenotype. Whole exome sequencing performed by Veritas Genetics, and independent dyslipidemia and ASCVD genetic risk testing by GB Healthwatch, revealed no pathogenic or likely pathogenic variants that could account for LM's phenotype.
Results of lipid panels conducted between August 2020 and October 2021, in conjunction with data extracted from LM's dietary records, are presented in  Table 1  and  Figure 1 . In August 2020, LDL-C was 521 mg/dl (HDL-C 113 mg/dl, TG 47 mg/dl). This time point corresponds to LM's BMI nadir of 18.8 kg/m2 and 83% unsaturated fat intake (17% saturated). In the following month, LM was recommended to reduce dietary cholesterol intake, eliminating liver, shellfish, and egg yolks from his diet (in substitution for lean chicken, fish, and egg whites). One month later, in September 2020, his LDL-C was re-measured at 545 mg/dl (HDL-C 94 mg/dl, TG 58 mg/dl). In January 2021, following a weight gain of 6 lbs and elevated intake of polyunsaturated fatty acid in the form of ~3 Tbsp toasted sesame oil daily, LDL-C was measured at 393 mg/dl (HDL-C 116 mg/dl, TG 40 mg/dl). Finally, testing in October 2021 following further weight gain of 4 lbs (BMI 20.2 kg/m2), and in the context of a diet far richer in saturated fat, LDL-C measured at 411 mg/dl (HDL-C 116 mg/dl, TG 39 mg/dl) ( Table 1  and  Figure 1 ).
After two and a half years of persistently elevated LDL-C levels, and a prior CAC of 0, LM was again counseled to initiate statin therapy. He considered, and a compromise was reached whereby he agreed to initiate pharmacotherapy if "it was first proven" that he was developing measurable atherosclerotic plaque. Given consideration of data available at the time in young people at elevated risk for ASCVD, and LM's significant exposure (LDL-C ~400-550 for ~2.5 years), a CCTA was ordered for calcified and non-calcified plaques. No plaque or stenosis was observed in any vessels CAD-RADS = 0 ( Figure 2 ).