Journal of clinical lipidology最新文献

Background: Apolipoprotein B (apoB) is a recognized risk factor for acute coronary syndrome (ACS); however, its prognostic value in secondary prevention and superiority over other lipid biomarkers, especially in younger populations, remains uncertain.

Objective: To investigate whether elevated baseline apoB predicts recurrent cardiovascular events in patients who experienced an ACS at ≤40 years of age and compare its incremental predictive value with that of other lipid biomarkers.

Methods: We recruited 405 consecutive patients who survived an ACS at ≤40 years of age. Clinical endpoints included major adverse cardiovascular events (MACE): cardiac death, readmission for ACS or ventricular arrhythmias, ischemic stroke, and coronary revascularization due to clinical deterioration. The association between baseline lipid biomarkers and recurrent MACE risk was assessed using multivariable Cox regression. Model performance was evaluated based on discrimination and reclassification.

Results: Of 378 young ACS survivors (33.7 ± 4.3 years) with follow-up data, 139 (36.8%) experienced a MACE over a median 8-year (5.2-12.5 years) follow-up. Elevated baseline apoB was independently associated with a higher risk of recurrent MACE (hazard ratio per 10 mg/dL: 1.082, P= .007). This association remained significant even after additionally accounting for low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C). Conversely, apoB adjustment attenuated the LDL-C and non-HDL-C associations. Compared with LDL-C and non-HDL-C, apoB was associated with greater risk of recurrent MACE, and upon addition to conventional cardiovascular risk factors, yielded the greatest improvement in discrimination and reclassification.

Conclusion: Baseline apoB may act as a driver for long-term recurrence of MACE in very young ACS survivors, highlighting its potential clinical utility to improve risk stratification beyond traditional lipid measurements.

Background: Remnant cholesterol (RC) is a modifiable risk factor for stroke in the general population; however, its role in stroke risk among patients with atrial fibrillation (AF) remains unclear.

Objective: This study aimed to examine the associations between key RC metrics, including baseline levels, cumulative measures, average real variability (ARV), and RC/low-density lipoprotein cholesterol (LDL-C) discordance, and stroke risk in patients with AF.

Methods: A total of 2154 patients with AF from the Atherosclerosis Risk in Communities database were analyzed. RC was calculated as total cholesterol minus LDL-C and high-density lipoprotein cholesterol. Cox proportional hazards models were used to assess the associations of 4 key RC metrics with stroke risk, adjusting for potential confounders.

Results: Higher baseline RC levels were significantly associated with an increased risk of stroke, with an adjusted hazard ratio (HR) of 1.41 (95% CI: 1.02-1.94, P = .039). This association was linear (P overall = .008). Each 1-SD increase in RC corresponded to a 11% higher stroke risk (HR = 1.11, P = .039). Similar associations were observed for ARV (HR = 2.06, P = .041) and cumulative RC levels (HR = 1.11, P = .002). Additionally, the concordant high RC/LDL-C group was linked to a higher stroke risk (HR = 1.93, P = .01).

Conclusion: Elevated RC baseline levels, variability, and cumulative exposure are independently associated with an increased risk of stroke in patients with AF, highlighting the need for lipid-lowering interventions targeting RC levels to mitigate stroke risk in this high-risk population.

Background: Observational and genetic evidence show associations of high remnant cholesterol levels with atherosclerotic cardiovascular disease (ASCVD). New drugs have been developed that substantially lower remnant cholesterol; however, the corresponding absolute risk reduction of ASCVD remains unclear. Remnant cholesterol can be measured directly or calculated, but few studies have analyzed the effects of directly measured remnant cholesterol.

Objective: To estimate the 10-year absolute risk reductions of ASCVD according to proportional reduction of individual very low-density lipoprotein (VLDL) cholesterol levels among individuals with levels above 1 mmol/L (39 mg/dL).

Methods: We used VLDL cholesterol measured by nuclear magnetic resonance spectroscopy to quantify directly measured remnant cholesterol. We estimated the reduction in the average 10-year ASCVD risk associated with an intervention targeting the 2021 individuals in the Copenhagen General Population Study with VLDL cholesterol levels above 1 mmol/L (39 mg/dL), assuming a proportional reduction in their individual VLDL cholesterol levels.

Results: We found that a 50% or 80% proportional reduction in VLDL cholesterol was associated with a 10-year absolute risk reduction of ASCVD of 3.0% (95% CI: 2.6%-3.4%) and 4.5% (3.9%-5.1%), respectively.

Conclusion: This suggests a clinically meaningful benefit from lowering of VLDL cholesterol in primary prevention.

Background: To examine associations between metabolic syndrome (MetS), its components, and MetS subgroups based on the absence or presence of hypertension (HTN) and diabetes mellitus (DM), with incident myocardial infarction (MI).

Methods: Among 7824 Tehran Lipid and Glucose Study participants (mean age 46.9 years; 44.9% men) without baseline cardiovascular disease, multivariable Cox models and restricted cubic spline analyses assessed the associations of MetS, its subgroups, and components with incident MI.

Results: Of the 7824 participants included, 4092 (52.3%) were free of MetS. Among participants with MetS, 1847 (49.5%) had neither DM nor HTN, 1217 (32.6%) had HTN only (DM-/HTN+), 330 (8.8%) had DM only (DM+/HTN-), and 338 (9.1%) had both DM and HTN (DM+/HTN+). During a median follow-up of 19.9 years, 252 MI events occurred. Compared with MetS-free individuals, the adjusted hazard ratio (HR) of MetS for incident MI was 2.04 (95% CI: 1.54-2.70). HRs were 1.41 (1.00-1.99) for MetS (DM-/HTN-), 2.06 (1.44-2.95) for MetS (DM-/HTN+), 3.40 (2.15-5.38) for MetS (DM+/HTN-), and 5.09 (3.33-7.81) for MetS (DM+/HTN+) subgroups. Individuals with MetS but without the elevated glucose component or HTN were still at increased risk of MI. Using the American College of Cardiology/American Heart Association definition of HTN did not alter the findings. All MetS components showed significant associations with MI. After adjustment for the other MetS components, elevated waist circumference (HR: 1.47, 95% CI: 1.09-1.98) and elevated blood pressure (1.50; 1.14-1.98) components were associated with higher risk of MI.

Conclusion: MetS in the absence of HTN and DM conferred a greater risk of MI.

Background: National epidemiologic data are needed to inform country-specific healthcare policies for prevention and new developing treatments.

Objective: We aimed to analyze Greek epidemiologic data in clinically relevant special populations for targeted treatments and to evaluate the utility of lipoprotein(a) [Lp(a)] as a risk enhancer METHODS: Two independent cohorts were included in this analysis: (1) consecutively recruited patients assessed in a tertiary outpatients' lipid clinic (Athens Angiometabolic cohort [AAC], n = 1106) with available peripheral vascular markers, and (2) sample of the Greek general population (ATTICA study [AS], n = 2682) with available 20-year follow-up data for atherosclerotic cardiovascular disease (ASCVD) events.

Results: Increased Lp(a) was found in 8.3% of the AS (≥50 mg/dL) and in 18.9% of the AAC (≥125 nmol/L) (16.0% without ASCVD and 22.1% with ASCVD, P = .006). Elevated Lp(a) levels were associated with increased carotid, coronary artery, and lower extremity atherosclerosis (P < .05 for all). Both the European Atherosclerosis Society (EAS) recommendations (net reclassification index [NRI]: 0.170) and a derived sex-specific inflation factor for HellenicSCOREII+ (NRI: 0.176) were efficient in incorporating Lp(a) as a risk enhancer over HellenicSCOREII+ for 20-year major adverse cardiovascular events. For 10-year cardiovascular death, only the EAS consensus provided significant reclassification. Finally, Lp(a) conferred increased eligibility for more aggressive primary prevention measures both by EAS recommendations (23.6% in AAC/13.6% in AS) and by sex-specific inflation factors (25.6% in AAC/22.3% in AS).

Conclusion: Elevated Lp(a) levels were observed in 8.3% of the general population cohort and up to 23.9% in participants with ASCVD from the lipid clinic cohort, highlighting a risk gradient across ASCVD categories. Incorporating Lp(a) as a risk enhancer improves ASCVD risk reclassification beyond the validated HellenicSCOREII+.

Background: Although familial hypercholesterolemia (FH) is a US Centers for Disease Control and Prevention tier 1 condition for genetic testing, the impact of testing on clinical outcomes is unclear.

Objective: We aimed to assess whether genetic testing alters lipid management in HeartCare participants.

Methods: For participants with pathogenic/likely pathogenic variants for FH observed at Baylor College of Medicine cardiology clinics, data on laboratory values, medication prescriptions, and diagnoses were collected and compared before and after genetic testing.

Results: In the 20 participants with APOB/LDLR variants and complete data, low-density lipoprotein cholesterol (LDL-C) was numerically lower but not significantly different before vs after genetic testing (103 vs 79.5 mg/dL). Sixteen (80%) participants were from the lipid clinic; the majority had a preexisting FH diagnosis. LDL-C levels were numerically lower, and more patients received proprotein convertase subtilisin/kexin type 9 inhibitor prescriptions after genetic testing; however, the difference was not statistically significant.

Conclusions: The majority of patients with FH achieved LDL-C <100 mg/dL after genetic testing; however, most patients with APOB/LDLR variants were from the lipid clinic and had been diagnosed with FH by clinical criteria.

Background: Obesity is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). While lowering low-density lipoprotein cholesterol (LDL-C) reduces ASCVD, it remains unclear whether patients with obesity exhibit distinct plaque responses to LDL-C control.

Objective: The current study sought to compare disease progression under achieving LDL-C <1.8 mmol/L in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) with and without obesity.

Methods: This prespecified sub-analysis of the OPTIMAL randomized trial (jRCT1052180152; UMIN000036721) evaluated 78 statin-treated patients with T2DM and CAD who underwent serial intravascular ultrasound imaging. Change in percent atheroma volume (PAV) was compared in those with obesity (body mass index [BMI] ≥ 25 kg/m², n = 31) and without (BMI <25 kg/m², n = 47) stratified by achievement of LDL-C<1.8 mmol/l at 48 weeks.

Results: LDL-C<1.8 mmol/L was attained in 41.9% with obesity and 57.4% without (P = .18). In participants without obesity, achieving LDL-C<1.8 mmol/L was not associated with significant change in PAV (-0.5 ± 0.4 vs -0.3 ± 0.4%, P = .74) or regression frequency (59.3 vs 62.0%, P = .85). In contrast, patients with obesity achieving LDL-C<1.8 mmol/L more often received high-intensity statins and demonstrated significant PAV regression (-0.9 ± 0.3 vs 0.4 ± 0.2%, P = .006) and greater regression frequency (79.6 vs 25.2%, P = .01).

Conclusion: A greater regression of coronary atheroma following LDL-C<1.8 mmol/L was observed in obese patients. Future dedicated study is warranted to further elucidate atheroma regression in response to LDL-C control in obese and nonobese patients.

Background: While lipids are known prognostic markers in coronary heart disease (CHD), the long-term impact of cumulative low-density lipoprotein cholesterol (cum-LDL-C) and the duration of high LDL-C exposure remains unclear.

Objective: This study aimed to evaluate their association with major adverse cardiovascular events (MACE) in patients with CHD.

Methods: We included 1271 patients initially diagnosed with CHD between 2018 and 2023, each with at least 2 follow-up records. Time-weighted cum-LDL-C was calculated and categorized by quartiles (Q1-Q4). Duration of high LDL-C exposure was grouped as 0, 0-2, >2 years. Cox models were used to estimate hazard ratios (HRs) and 95% CIs for MACE, all-cause mortality, and other cardiovascular outcomes. A nomogram was developed for clinical risk scoring.

Results: Over a median follow-up of 1293 days, 196 patients experienced MACE. After multivariable adjustment, the highest cum-LDL-C quartile (Q4) showed significantly increased risks of MACE (HR: 3.50, 95% CI: 2.24-5.47), percutaneous coronary intervention (HR: 3.08, 1.41-6.71), and ischemic stroke (HR: 4.32, 2.25-8.30). Exposure to high LDL-C for >2 years was associated with a 1.68-fold higher MACE risk (95% CI: 1.18-2.40) and a 2.09-fold higher ischemic stroke risk (95% CI: 1.34-3.27). No significant associations were found with all-cause mortality or myocardial infarction.

Conclusion: Both elevated cum-LDL-C and prolonged exposure to high LDL-C are associated with increased risks of MACE in patients with CHD. Extending lipid monitoring periods may help clarify cumulative risk and improve clinical management.