The Assessment of Carotid Atherosclerotic Plaque among Young Patients with Familial Hypercholesterolemia.

Objective Few data exist regarding when atherosclerotic changes occur among patients with familial hypercholesterolemia (FH). Carotid ultrasonography is a non-invasive method of evaluating this issue. The present study (1) compared the clinical utilities of carotid intima-media thickness (cIMT) and carotid plaque score (cPS) and (2) estimated the onset and progression of carotid atherosclerosis among patients with heterozygous FH (HeFH). Methods We retrospectively analyzed 511 patients under 30 years old who underwent carotid ultrasonography at our hospital from 2006 to 2019. We classified them into the HeFH group (n=78, 21.4±5.9 years old) and non-FH group (n=433, 23.4±6.0 years old) based on the clinical diagnosis and compared their cIMT and cPS values. In addition, we estimated the onset and progression of carotid atherosclerosis among young HeFH patients. Results There was no significant difference in the cIMT between the HeFH and non-FH groups (0.44 mm vs. 0.42 mm, p=0.25). In contrast, the cPS was significantly higher in the HeFH group than in the non-FH group (1.11 vs. 0.26, p=0.002). The regression equation for cPS of HeFH group was Y=-2.05+0.15X (r=0.37, p<0.001). Conclusion An assessment based on the cPS rather than the cIMT appears to be better to capture the progress of carotid atherosclerosis among young HeFH patients. Carotid atherosclerosis may start to develop at 14 years old in patients with HeFH.

Efficacy and Safety of Clopidogrel, Prasugrel and Ticagrelor in ACS Patients Treated with PCI: A Propensity Score Analysis of the RENAMI and BleeMACS Registries.

INTRODUCTION: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. METHODS: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. RESULTS: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events. CONCLUSION: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.

Quick sepsis-related organ failure assessment score as a possible predictor for in-hospital adverse events in infective endocarditis.

AIM: Infective endocarditis (IE) can be life-threatening because of various associated adverse events. The quick Sepsis-related Organ Failure Assessment (qSOFA) score is a straightforward useful method for predicting in-hospital mortality in patients with suspected infections. However, few data exist regarding the clinical impact of the qSOFA score on predicting adverse events in IE during hospitalization. We studied the usefulness of qSOFA score for predicting in-hospital adverse events in patients with IE. METHODS: We retrospectively analyzed 104 consecutive patients diagnosed with IE on the basis of modified Duke criteria. We defined in-hospital adverse events as occurrence of any of the following events during hospitalization: death, embolism, hemorrhage, or abscess formation. The high qSOFA group was defined as those with a qSOFA score ≥2. We used Cox regression analysis to estimate the hazard ratio for high qSOFA score on in-hospital adverse events adjusted for age, sex, and Staphylococcus aureus infection. RESULTS: We analyzed 83 patients (57 men, mean age 61 ± 18 years) from the total cohort of 104 patients enrolled. Among these, 12 (14.5%) had high qSOFA scores. The high qSOFA group had higher in-hospital mortality compared to the low qSOFA group (50.0% vs. 4.2%, P < 0.01). In the Cox proportional hazards model, high qSOFA was significantly associated with in-hospital adverse events (adjusted hazard ratio, 2.29; confidence interval, 1.02-5.12; P = 0.044). CONCLUSION: These results showed that high qSOFA score was significantly associated with in-hospital adverse events in IE patients, although further prospective study is necessary to confirm our results.

Assessment of arterial stiffness in patients with familial hypercholesterolemia.

BACKGROUND: Recently, the concept of severe familial hypercholesterolemia (FH) has been proposed to identify individuals at an extremely high risk of developing coronary artery disease (CAD) among patients with FH. Although the adverse effects of arterial stiffness have been proven in the general population, insufficient data exist regarding its clinical impact in patients with FH. OBJECTIVES: This study aimed to assess the association between arterial stiffness and CAD in patients with FH. METHODS: We examined 245 patients with FH (162 males; mean age, 46 ± 17 years) and brachial-ankle pulse wave velocity (baPWV) measurements. We assessed baseline characteristics including lipid profiles, other traditional risk factors, the presence of CAD, and the baPWV. RESULTS: Multivariable logistic analysis adjusted for age, sex, hypertension, diabetes, smoking, and low-density lipoprotein cholesterol revealed that the baPWV was independently associated with CAD (odds ratio [OR]: 1.25, 95% confidence interval: 1.10-1.41; P = .000372; per 100 cm/s). Moreover, considering the baPWV with other traditional risk factors improved the risk discrimination of CAD (C-statistics 0.736 vs 0.799; P = .006067). Compared with the reference group without hypertension and low baPWV, patients with hypertension and high baPWV had a significantly higher OR for CAD (OR: 18.68, 95% confidence interval: 6.62-60.62; P = 1.7 × 10-7). CONCLUSIONS: Arterial stiffness assessed by the baPWV was significantly associated with the presence of CAD in patients with FH. Such assessments are useful in the risk stratification of CAD and are independent of hypertension in patients with FH.

Assessment of coronary atherosclerosis in patients with familial hypercholesterolemia by coronary computed tomography angiography.

The aims of this study were (1) to determine whether the accumulation of coronary plaque burden assessed with coronary computed tomography angiography (CCTA) can predict future events and (2) to estimate the onset and progression of coronary atherosclerosis in patients with familial hypercholesterolemia (FH). Consecutive 101 Japanese patients with heterozygous FH (men = 52, mean age 56 ± 16 years, mean low-density lipoprotein cholesterol 264 ± 58 mg/dl) who underwent 64-detector row CCTA without known coronary artery disease were retrospectively evaluated by assigning a score (0 to 5) to each of 17 coronary artery segments according to the Society of Cardiovascular Computed Tomography guidelines. Those scores were summed and subsequently natural log transformed. The periods to major adverse cardiac events (MACE) were estimated using multivariable Cox proportional hazards models. During the follow-up period (median 941 days), 21 MACE had occurred. Receiver operating characteristic curve analyses identified a plaque burden score of 3.35 (raw score 28.5) as the optimal cutoff for predicting a worse prognosis. Multivariate Cox regression analysis identified the presence of a plaque score ≥3.35 as a significant independent predictor of MACE (hazard ratio = 3.65; 95% confidence interval 1.32 to 25.84, p <0.05). The regression equations were Y = 0.68X - 15.6 (r = 0.54, p <0.05) in male and Y = 0.74X - 24.8 (r = 0.69, p <0.05) in female patients with heterozygous FH. In conclusion, coronary plaque burden identified in a noninvasive, quantitative manner was significantly associated with future coronary events in Japanese patients with heterozygous FH and that coronary atherosclerosis may start to develop, on average, at age 23 and 34 years in male and female patients with heterozygous FH, respectively.

Lipoprotein metabolism in familial hypercholesterolemia: Serial assessment using a one-step ultracentrifugation method.

OBJECTIVES: It is well known that familial hypercholesterolemia (FH) is a common inherited disorder that can markedly elevate the level of plasma LDL cholesterol. However, little data exists regarding the clinical impact of the plasma triglyceride (TG)-rich lipoprotein fraction, including VLDL and IDL, in FH. Thus, we assessed the hypothesis that the mutations in the LDL receptor modulate lipoprotein metabolism other than the LDL fraction. DESIGN AND METHODS: We investigated plasma lipoprotein with a one-step ultracentrifugation method for 146 controls (mean age=61.4±17.1 yr, mean LDL cholesterol=92.7±61.2 mg/dl), 213 heterozygous mutation-determined FH subjects (mean age=46.0±18.0 yr, mean LDL cholesterol=225.1±61.2 mg/dl), and 16 homozygous/compound heterozygous mutation-determined FH subjects (mean age=26.9±17.1 yr, mean LDL cholesterol=428.6±86.1 mg/dl). In addition, we evaluated cholesterol/TG ratio in each lipoprotein fraction separated by ultracentrifugation. RESULTS: In addition to total cholesterol and LDL cholesterol levels, VLDL cholesterol (19.5±10.4, 25.2±19.3, 29.5±21.4 mg/dl, respectively) and IDL cholesterol (8.3±3.7, 16.8±11.5, 40.0±37.3 mg/dl, respectively) exhibited a tri-model distribution according to their status in LDL receptor mutation(s). Moreover, the ratios of cholesterol/TG of each lipoprotein fraction increased significantly in heterozygous FH and homozygous/compound heterozygous FH groups, compared with that of controls, suggesting that the abnormality in LDL receptor modulates the quality as well as the quantity of each lipoprotein fraction. CONCLUSIONS: Our results indicate that cholesterol in TG-rich lipoproteins, including VLDL and IDL, are significantly higher in FH subjects, revealing a tri-modal distribution according to the number of LDL receptor mutations.