Journal of clinical lipidology最新文献

Background/Synopsis

Limited data exist regarding familial hypercholesterolemia (FH) diagnosis and treatment in diverse populations.

Objective/Purpose

We sought to assess patient characteristics and current treatment patterns among individuals with FH and/or elevated low-density lipoprotein cholesterol (LDL-C) in a diverse real-world cohort within the United States.

Methods

We examined data from the NIH Precision Medicine Initiative All of Us Research Program, a cross-sectional study beginning in 2015 inclusive of historically underrepresented groups. Among participants with >1 LDL-C measurement, we examined lipid-lowering medication utilization and treatment patterns among participants with and without FH diagnosis stratified by LDL-C. We additionally examined whether sex differences existed in treatment and diagnosis.

Results

Among 369,483 All of Us participants age ≥18 years, our study sample included 113,153 individuals who had at least one LDL-C measurement. Of these, 4018 (3.5%) had LDL-C ≥160 mg/dL, 733 (0.26%) had LDL-C ≥190 mg/dL, and 434 were diagnosed with FH (0.37%). Statin usage was found to be higher among men compared to women both in those with FH (84% vs. 70.3%, p=0.002) and without FH (54.2% vs. 39.2%, p<0.001) irrespective of LDL-C measures. Women tended to have higher mean LDL-C levels compared to men (130.9 mg/dL vs. 105.8 mg/dL, p<0.001 in those with FH and 106.9 mg/dL vs. 98.8 mg/dL p<0.001 in those without FH). Participants with FH were also more likely to be on statin therapy (75.2% vs 44.8%, p-value <0.001) with 18.4% on two or more types of lipid-lowering agents. Despite this, a higher percentage of FH participants had a history of >1 major ASCVD event (19.4% vs 10.7%, p-value <0.001), and exhibited higher mean LDL-C levels (121.9 mg/dL vs 103.9 mg/dL) compared to non-FH participants. Notably, only 30.5% of FH participants achieved the recommended LDL-C<100 mg/dL compared to 45.7% of those without FH (p-value<0.001). Furthermore, a majority (60.6%) of those already diagnosed with FH had LDL-C <130 mg/dL, including those not taking a lipid-lowering drug (Figure 1), questioning whether FH is being incorrectly diagnosed in some patients.

Conclusions

This study highlights the under and possible inappropriate diagnosis of FH and inadequate treatment of those diagnosed with FH among a real-world population.

Background/Synopsis

Lipoprotein A [(Lp(a)] has known atherogenic and thrombotic properties. We present a young patient with recurrent transient ischemic attacks (TIA) and ischemic stroke who was found to have hyperlipidemia and elevated Lp(a) levels. In patients with increased risk of atherosclerosis, screening guidelines recommend checking Lp(a) levels once. This case emphasizes the importance of obtaining Lp(a) levels in young patients with cardiovascular risk factors and appropriate medical therapy.

Objective/Purpose

Describe the importance of Lp (a) screening in young patients.

Methods

Medical record review.

Results

A 49-year-old African American male with a past medical history of anxiety and seizures presented with left sided numbness and paresthesia. Family history was remarkable for diabetes and hypertension. He was diagnosed with a TIA. His LDL-C was 214mg/dL. He was started on atorvastatin 40mg and aspirin 81mg. He continued on this regimen despite uncontrolled LDL-C. Five years later, the patient presented with visual disturbances and headache and was found to have a PCA stroke. A TTE with bubble was negative for PFO and ASD. Holter monitor was unrevealing for arrhythmia. He was started on ezetimibe 10mg and atorvastatin was increased to 80mg. 

One year later, he presented with episodic dizziness. CTA head and neck revealed a basilar TIA.  Laboratory results showed LDL-C 140mg/dL. Lp(a) was obtained as prior workup had been equivocal and was 356.7nmol/L (ref. <75nmol/L). He was started on PCSK9 therapy in addition to his other lipid lowering therapies.

Conclusions

This patient presented with stroke and was found to have an LDL-C above 200mg/dL which should have prompted aggressive medical therapy, lifestyle modifications and close follow-up. He remained on the same medications despite uncontrolled LDL-C. Elevated Lp(a) was discovered only after the patient had suffered multiple events. On average, African American patients have higher Lp(a) levels compared to Caucasian and Asian patients, however this patient's Lp(a) levels are significantly higher than what can be solely attributed to race. It is likely that obtaining Lp(a) during the first event could have changed his clinical course over the years. This case emphasizes the importance of timely Lp(a) screening and prompt intervention.

Background/Synopsis

RG is a 43-year-old male with fatty liver disease, found to have low total and low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) levels.

Objective/Purpose

To review a clinical scenario where making the proper lipid/lipoprotein diagnosis explains the background common coincident condition (fatty liver).

Methods

Patient was seen in the office at Lipid Clinic at Penn for further evaluation.

Results

RG is a 43-year-old obese male is referred to lipid clinic for further evaluation after initial presentation of abnormal liver function tests and very low cholesterol. There is a longstanding >15 years history of abnormal liver function tests and radiographic suspicion of fatty liver disease and liver biopsy showing moderate macrovesicular steatosis with mild steatohepatitis.

Genetic testing confirmed a pathogenic variant in the APOB gene associated with a diagnosis of autosomal dominant familial hypobetalipoproteinemia (FHBL). FHBL is primarily caused by pathogenic changes in the APOB gene but it has also been associated with pathogenic variants in other genes, including ANGPTL3 and PCSK9.

This condition is associated with a low risk of developing atherosclerotic cardiovascular disease (ASCVD) and high risk for development of fatty liver disease.

RG has coronary artery calcium score (CACS) = 0. He was counseled on natural history and inheritance pattern of this condition. There is no pharmacologic treatment required, but he was advised to supplement with fat-soluble vitamins and follow up with his primary team for ongoing care of liver disease.

Conclusions

Familial hypobetalipoproteinemia (FHBL) is a monogenic lipid disorder, characterized by low total and LDL-C. This condition is due to mutations in APOB gene that disrupts normal apoB protein synthesis. This condition is typically well-tolerated, but can be a cause of fatty liver disease and even cryptogenic cirrhosis. It is important to identify the correct cause of fatty liver disease since it may be reversible and because patients regularly report feeling accused by health professional when questioned about alcohol consumption or other lifestyle transgressions as a cause of their disease. Clarification of the diagnosis will enable proper lifestyle counseling and care.

Background/Synopsis

Severe hypertriglyceridemia (HTG), greater than 1,000 mg/dL, is frequently due to a pathological accumulation of circulating chylomicrons, termed chylomicronemia. This can lead to plasma hyperviscosity with decreased perfusion, manifesting as acute pancreatitis, impaired cognition, and neuropathy. Given the lack of established guidelines, managing symptomatic chylomicronemia underscores the necessity for personalized expert care.

Objective/Purpose

To review the unusual presentations and inpatient management of chylomicronemia syndrome.

Methods

We present two cases of symptomatic, severe HTG, each managed with different treatment modalities.

Results

Case 1: A 35-year-old man, with a history of uncontrolled T2DM, hypertension (HTN), and HTG, presented with a persistent, throbbing headache (HA). His exam was unremarkable. Clinical investigation revealed severe HTG (9,157 mg/dL; normal 30-150) with normal abdominal and brain imaging. Inpatient management included nothing by mouth (NPO), intravenous (IV) fluids, and insulin infusion, which led to a gradual decline in TG to 1,341 mg/dL. HA resolution occurred after 7 days of therapy. The patient was educated on a very low-fat diet, strict glycemic control, lipid lowering therapy compliance, and scheduled outpatient follow-up.

Case 2: A 43-year-old woman, with a history of uncontrolled T2DM, HTN, and pancreatitis due to HTG, presented with a HA and abdominal pain one week after running out of her medications. Her exam was notable for a blood pressure of 180/96 mmHg, eruptive xanthomas on the extensor surfaces of the extremities, and abdominal tenderness. She was diagnosed with HTG-induced acute pancreatitis, supported by a TG of 5,307 mg/dL, elevated lipase levels (86 U/L; normal 5-55), and CT findings of an edematous pancreas with surrounding fat stranding. The patient was made NPO and treated with IV fluids and insulin infusion. On the 5th day of admission, due to persistently elevated TG and an ongoing HA, plasmapheresis was initiated. After a single session, TG decreased from 2,048 mg/dL to 534 mg/dL, and the patient's symptoms resolved. Prior to discharge, she was restarted on atorvastatin, fenofibrate, and omega-3 acid ethyl esters.

Conclusions

Managing severe, symptomatic HTG includes NPO status, insulin infusion, and oral lipid lowering therapies; often requiring prolonged hospitalization. Plasmapheresis, though costly and invasive, offers a rapid reduction in TG, symptom resolution, and prevention of HTG-associated complications. Future studies on these treatment modalities can aid in developing inpatient management guidelines for chylomicronemia syndrome.

Background/Synopsis

In recent years, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated significant benefits in both cardiovascular and renal outcomes, which has resulted in increased provider utilization and inclusion into society guidelines. As the use of SGLT2i expands, variations in prescribing practices may arise.

Objective/Purpose

To identify variations in prescribing practices in SGLT2i among patients of different sex with either congestive heart failure (CHF) or chronic kidney disease (CKD).

Methods

A cross-sectional analysis of all patients prescribed SGLT2i between 2018 and 2023 within the Northwell Health system in New York State was conducted. Demographic data, including race, sex, ICD-10 codes for CHF and CKD, and last documented GFR, were retrieved from the electronic medical record. Patients were considered to have CKD with an appropriate indication for SGLT2i if they had an ICD-10 code for CKD or a GFR between 30 and 60. This data was then compared to the prevalence of CHF and CKD in men and women as reported in the Medicare Current Beneficiaries Survey (MCBS) of Fall 2021.

Results

From 2018 to 2023, of the 11,290 patients were prescribed SGLT2i, 12.7% had CHF and 10.5% had CKD. Of the patients with CHF, 27.6% were women, and of the patients with CKD, 33.9% were women. Within MCBS, women comprised 48.9% of patients with CHF and 51.9% of patients with CKD.

Conclusions

While according to MCBS, CHF and CKD affect men and women in approximately equal proportions, our data suggests that less women were prescribed SGLT2i. This discrepancy may represent different prevalence of CHF and CKD in men and women in New York State, contraindications to SGLT2i that are more likely to be present in women, or a systematic bias. Alternatively, prescribers may be hesitant to prescribe SGLT2i to women, given the FDA warning regarding increased risk of genitourinary infections. Ultimately, this study reveals a potential underlying bias in prescribing practices for SGLT2i between men and women that would benefit from further study and enhanced clinician awareness.

Background/Synopsis

Individuals with NAFLD may have alterations in lipid metabolism, insulin resistance, and an increased risk of dyslipidemia, all of which can contribute to the development of acute pancreatitis. Dyslipidemia, particularly elevated triglycerides and low-density lipoprotein cholesterol (LDL-C), is often seen in individuals with NAFLD. Insulin resistance and metabolic syndrome are common underlying factors.

Objective/Purpose

There is limited scientific evidence of clinical outcomes of NAFLD in patients admitted with acute pancreatitis & dyslipidemia. Hence, we sought to investigate this population.

Methods

We queried National Inpatient Sample between 2017-2020 for adult patients who were hospitalized with acute pancreatitis & dyslipidemia with NAFLD. The primary outcome was inpatient mortality. The secondary outcomes were cardiogenic shock, cardiac arrest, gastrointestinal bleeding (GIB), acute kidney injury (AKI), intubation, length of stay (LOS) and total hospital charge. Multivariable logistic regression analysis was used to estimate clinical outcomes. P-value < 0.05 was significant.

Results

There were 574,269 hospitalizations with acute pancreatitis and dyslipidemia where 29,324 (5.1%) had NAFLD. NAFLD and non-NAFLD cohorts were with mean age of 61.5 vs. 60 yrs; males 54.5% vs 56.2%; Caucasians 65.0% both; HTN 49% vs 56%; HF 18.8% vs 12%; obesity 27% vs 24%; Metabolic Syndrome 9.6% vs 8.7%; DKA 3.9% vs 4.9%; AF 24.4% vs 23.5%; AKI 38% vs 21.8%; obesity 30.3% vs 29.3%; ACS 6.6% vs 2.8%; acute respiratory failure 17.8% vs 6.4%; history of stroke 0.9% vs 0.4%; COPD 15% vs 13.5%; alcohol use 19.9% vs 18.5%, respectively. NAFLD cohort had significantly higher mortality and worse clinical outcomes (Table 1).

Conclusions

NAFLD group demonstrated significantly higher mortality, worse clinical outcomes and resource utilization. Patients were older, obese, female, same Caucasian population, with more frequent HF, AF, ACS and alcohol use. NAFLD is associated with greater risk for cardiovascular events, renal failure, GIB, and ICU care. NAFLD is an important predictor of adverse outcomes in acute pancreatitis & dyslipidemia population. Further research is necessary to describe long-term outcomes.

BACKGROUND

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been pivotal in the management of type 2 diabetes mellitus (T2DM) and in the reduction of major adverse cardiovascular events (MACE). Notably, large cardiovascular outcomes trials (CVOTs) demonstrate significant disparities in inclusion, based on sex, race, ethnicity, and geographical regions.

OBJECTIVES

We examined the impact of GLP-1RA on MACE in patients with or without T2DM, based on sex, race, ethnicity, and geography.

METHODS

A literature search for placebo controlled randomized controlled trials on GLP-1RA treatment was conducted. Thorough data extraction and quality assessment were carried out, focusing on key outcome, and ensuring a robust statistical analysis using a random effects model to calculate log odds ratio (OR) with 95% confidence intervals (CIs).

RESULTS

A total of 8 CVOTs comprising 71,616 patients were included. Compared with placebo, GLP-1RAs significantly reduced MACE in both sexes (females: logOR -0.19, (95% CI, -0.28 to -0.10), p < 0.01) versus (males: logOR -0.17, (95% CI, -0.23 to -0.10), p < 0.01), (p interaction NS), and among Asians (logOR -34 (95% CI, -0.53 to -0.15), p < 0.01), and Whites (logOR -17 (95% CI, -0.25 to -0.09), p < 0.01), with no difference in MACE among Blacks and Hispanics. Odds of MACE were also reduced in Asia (logOR -31 (95% CI, -0.50 to -0.11), p < 0.01), and Europe (logOR -27 (95% CI, -0.40 to -0.13), p < 0.01), but there was no statistical difference in MACE in North America and Latin America.

CONCLUSION

Significant reductions in MACE with GLP-1RA treatment were demonstrated between both sexes and across certain ethnicities and certain geographical regions.