Background: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; mid-term (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after PCI with DES. Methods: Twenty-four randomized controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The co-primary endpoints were myocardial infarction (MI) and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with random effects model. Results: In 79,073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of MI compared with 12-month DAPT (absolute risk difference [ARD], -3.8 incident cases per 1000 person-years; relative risk (RR), 0.68 [95% CI, 0.54-0.87]), mid-term DAPT (ARD, -4.6 incident cases per 1000 person-years; RR, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (ARD, -6.1 incident cases per 1000 personyears; RR, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (ARD, -3.7 incident cases per 1000 person-years; RR, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding compared with all other DAPT groups. Compared with 12-month DAPT, no significant differences in the risks of ischemic endpoints or major bleeding were observed with mid-term or short-term DAPT followed by aspirin monotherapy, except that shortterm DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome (ACS), extended-term compared with 12-month DAPT was associated with a reduced risk of MI without significant increase in the risk of major bleeding. Conclusions: The present network meta-analysis suggests that compared with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after PCI with DES, while extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.

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Higher baseline high-sensitivity C-reactive protein (hsCRP) levels after an acute coronary syndrome (ACS) are associated with adverse cardiovascular outcomes. The usefulness of serial hsCRP measurements for risk stratifying patients after ACS is not well characterized. OBJECTIVE To assess whether longitudinal increases in hsCRP measurements during the 16 weeks after ACS are independently associated with a greater risk of a major adverse cardiac event (MACE), all-cause death, and cardiovascular death. DESIGN, SETTING, AND PARTICIPANTS Secondary analysis of the double-blind, multicenter, randomized clinical Vascular Inflammation Suppression to Treat Acute Coronary Syndromes for 16 Weeks (VISTA-16) trial conducted between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012), which included 5145 patients from 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America assigned to receive varespladib or placebo on a background of atorvastatin treatment beginning within 96 hours of presentation with an ACS. The present study evaluated data from patients with available baseline and longitudinal hsCRP levels measured at weeks 1, 2, 4, 8, and 16 after randomization to treatment or placebo. Statistical analysis was performed from June 15, 2018, through September 15, 2018. MAIN OUTCOMES AND MEASURES Outcomes were MACE (composite of cardiovascular death, myocardial infarction, nonfatal stroke, or unstable angina with documented ischemia requiring hospitalization), cardiovascular death, and all-cause death after adjustment for baseline clinical, treatment, and laboratory characteristics, including baseline hsCRP levels. RESULTS Among 4257 patients in this study, 3141 (73.8%) were men and the mean age was 60.3 years (interquartile range [IQR], 53.5-67.8 years). The median 16-week low-density lipoprotein cholesterol level was 64.9 mg/dL (IQR, 50.3-82.3 mg/dL), and the median hsCRP level was 2.4 mg/L (IQR, 1.1-5.2 mg/L). On multivariable analysis, higher baseline hsCRP level (hazard ratio [HR], 1.36 [95% CI, 1.13-1.63]; P = .001) and higher longitudinal hsCRP level (HR, 1.15 [95% CI, 1.09-1.21]; P < .001) were independently associated with MACE. Similar significant and independent associations were shown between baseline and longitudinal hsCRP levels and cardiovascular death (baseline: HR, 1.61 per SD [95% CI, 1.07-2.41],

Aim Remnant cholesterol has been proposed to promote atherosclerotic cardiovascular disease independent of low-density lipoprotein cholesterol, yet the underlying mechanisms are not well understood. We aimed to study the association of remnant cholesterol with coronary atheroma progression and clinical events. Methods We analyzed data from 5754 patients with coronary artery disease undergoing serial intravascular ultrasonography who were enrolled in 10 trials examining various medical therapies. Remnant cholesterol was calculated as (non-high-density lipoprotein cholesterol – low-density lipoprotein cholesterol (estimated using the Hopkins–Martin equation)). Changes in percentage atheroma volume and 2-year major adverse cardiovascular events were compared across various levels of remnant cholesterol, and multivariable models were used to assess the independent relationship of remnant cholesterol with changes in percentage atheroma volume. Results The mean age was 58.1 ± 9.2 years, 28% were women and 96% received a statin. Percentage atheroma volume progression (changes in percentage atheroma volume > 0) occurred in a linear fashion at on-treatment remnant cholesterol levels of 25 mg/dL or greater. The highest on-treatment remnant cholesterol quartile demonstrated greater percentage atheroma volume progression (+0.53 ± 0.26 vs. –0.15 ± 0.25%, P < 0.001) and 2-year major adverse cardiovascular events (23% vs. 14%, log–rank P < 0.001) compared with the lowest. In multivariable analyses, changes in percentage atheroma volume significantly correlated with on-treatment remnant cholesterol ( P < 0.001] independent of low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein, high-density lipoprotein cholesterol levels and clinical risk factors. Changes in percentage atheroma volume also significantly correlated with changes in remnant cholesterol following multivariable adjustment. Conclusions In statin-treated patients with atherosclerotic cardiovascular disease, remnant cholesterol was associated with coronary atheroma progression regardless of conventional lipid parameters, C-reactive protein or clinical risk factors. Higher remnant cholesterol levels also correlated with higher major adverse cardiovascular events. These data support further investigations into remnant cholesterol-lowering interventions in statin-treated patients harboring residual atherosclerotic cardiovascular disease risk.

Wnt signaling is critical for proper development of the head and face in the mouse embryo, playing important roles in various aspects of craniofacial development ranging from axis formation to survival of cranial neural crest cells to patterning of the brain. The signaling requirements for the development of different cell lineages in the head and face are active areas of investigation. In this study, we use a recently developed TCF/Lef-LacZ transgenic reporter mouse to characterize the expression of canonical Wnt signaling activity during craniofacial development. We present an atlas of representative sections to show embryonic craniofacial development. Our results demonstrate a pattern of sustained Wnt signaling reporter activity in most tissues which suggests sequential roles in craniofacial development.

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Background For patients with autosomal dominant hypercholesterolemia (ADH), it remains unclear whether differences exist in the risk of premature coronary heart disease (CHD) between patients with confirmed mutations in low-density lipoprotein receptor (LDLR) vs those without detectable mutations. Objective This study sought to assess the risk of premature CHD in ADH patients with mutations in LDLR (referred to as Familial Hypercholesterolemia, FH) vs those without detectable mutations (unexplained ADH), stratified by sex. Methods Comparative study of premature CHD in a multiethnic cohort of 111 men and 165 women meeting adult Simon-Broome criteria for ADH. Results Women with FH (n = 51) had an increased risk of premature CHD compared to unexplained ADH women (n = 111) (hazard ratio [HR] 2.74 [95% CI: 1.40, 5.34], p = 0.003) even after adjustment for lipid levels and traditional CHD risk factors (HR 2.53 [1.10, 5.83], p = 0.005). Men with FH (n = 42), in contrast, had a similar risk of premature CHD when compared to unexplained ADH men (n = 66) (unadjusted: HR 1.48 [0.84, 2.63], p = 0.18; adjusted: HR 1.04 [0.46, 2.37] p = 0.72). To address whether mutation status provides additional information beyond LDL-C level, we analyzed premature CHD risk for FH vs unexplained ADH at each quartile of LDL-C: the findings were significant for women (Q1: HR 4.90 [1.69-14.19]; Q2: HR 3.44 [1.42-8.32]; Q3: HR 2.79 [1.25-6.23]; Q4: HR 1.99 [0.95-4.17]), but not for men. Conclusion Our findings suggest that genetic confirmation of ADH may be important to identify patient's risk of CHD, especially for female LDLR mutation carriers.

Systemic sclerosis, an autoimmune disease characterized by fi brosis of the skin and various internal organs, is associated with cardiovascular abnormalities including pulmonary hypertension, atherosclerosis, right and left ventricular dysfunction, arrhythmias, conduction defects, pericardial disease, and valvular heart disease. Clinicians caring for patients with this disease should regularly screen for cardiac symptoms, and patients with abnormal fi ndings should be managed in conjunction with a cardiologist to optimally modify cardiovascular risks. KEY POINTS Pulmonary hypertension is common in systemic sclerosis and carries a poor prognosis. Patients with systemic sclerosis should be screened regularly with echocardiography, followed, when necessary, by right heart catheterization to detect it early. Myocardial infarction and stroke are more common in patients with systemic sclerosis, and preventive measures are the same as for the general population. Right ventricular dysfunction secondary to pulmonary hypertension is common in systemic sclerosis; left ventricular dysfunction is less so. Routine echocardiography should include assessment of right and left ventricular function. Electrocardiography should be performed periodically, and urgently when indicated, to look for potentially dangerous arrhythmias.