JCL roundtable: Coronary artery calcium scoring and other vascular imaging for risk assessment

Computed tomographic (CT) coronary calcium scoring has been established by large prospective, population-based studies as the single best noninvasive predictor of atherosclerotic cardiovascular risk available today. The calcium score correlates highly with the total burden of coronary atherosclerosis demonstrated at autopsy. It adds significantly to traditional risk calculators such as the Framingham Risk Calculator or the Pooled Cohort Equations. The 2018 U.S. Cholesterol Guidelines endorse the use of CT coronary calcium scoring to refine risk estimates in the intermediate range of 7.5%–20% over 10 years. Most, but not all, adults with calcium scores of zero can reasonably elect to avoid or defer statin therapy, but repeating the calcium score should be considered in 5 to 10 years. Discussants at this roundtable urge that coronary calcium scoring be offered to many more adults than currently receiving this test, including those with borderline 10-year risk in the range of 5%–7.5%. CT coronary angiography is a procedure based on intravenous contrast injection, mostly used in low-risk patients with chest pain. In British guidelines, CT angiography is preferred over stress testing for initial assessment of suspected coronary symptoms. Carotid ultrasound evaluating both the carotid intima-media thickness and presence of plague is less predictive than coronary calcium scoring for overall atherosclerotic risk but more predictive for stroke risk.     

Symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent vitamin D deficiency leading to statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle

Myositis-myalgia is the most common cause of statin intolerance, leading to cessation of statin use, with consequent failure to lower LDL cholesterol to target levels for primary and secondary prevention of cardiovascular disease (CVD). We hypothesize that symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent 25 (OH) vitamin D deficiency and statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle. In hypercholesterolemic, vitamin D deficient patients, intolerant to statins because of myositis-myalgia, three non-blinded clinical case series have uniformly demonstrated that after supplementation with oral vitamin D2 which normalizes serum 25 (OH) vitamin D levels, statins can be successfully re-instituted in >90% of patients, without recurrent myositis-myalgia, with reduction of LDL cholesterol to target levels. Empirically, in 68 hypercholesterolemic patients, unable to tolerate ? 1 statin because of myositis-myalgia, selected by low (<32 ng/ml) serum 25 (OH) vitamin D, we have prospectively assessed whether resolution of vitamin D deficiency would result in statin tolerance, free of myositis-myalgia. On no statins, 50,000 units of vitamin D2 was given twice/week for 3 weeks, and was then continued once/week. After 3 weeks on vitamin D supplementation, statins were restarted, and patients were re-assessed after 3 months on statins while continuing vitamin D supplementation. At 3 months follow-up, on vitamin D supplementation and re-instituted statins, 62 of 68 (91%) previously statin-intolerant patients now tolerated statins well and were asymptomatic without myositis-myalgia. In these 68 patients, on vitamin D supplementation and statins, mean ± SD vitamin D rose from 22 ± 7 to 43 ± 13 ng/ml (p < 0.0001), and LDL cholesterol fell from 162 ± 55 to 101 ± 35 mg/dl (p < 0.0001). Despite published and new empirical evidence, the medical establishment has refused to accept the hypothesis, requiring placebo-controlled, double-blind studies, none having been reported to date. A placebo-controlled, double-blind study is needed to document that normalization of serum 25 (OH) vitamin D levels in vitamin D deficient, statin intolerant patients would facilitate re-introduction of statins with concurrent freedom from myositis-myalgia. The ability to reverse myositis-myalgia in vitamin D deficient, statin intolerant, hypercholesterolemic patients by vitamin D supplementation would be extraordinarily valuable, facilitating reinstitution of statins to lower LDL cholesterol to reduce risk of CVD events. We hypothesize that symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent vitamin D deficiency producing statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle.     

Effectiveness and tolerability of ezetimibe co-administered with statins versus statin dose-doubling in high-risk patients with persistent hyperlipidemia: The EZE(STAT)2 trial

Introduction

When a standard dose of statins fails to achieve lipid control in patients at high risk for coronary artery disease (CAD), increasing the statin dosage or co-administration of additional agents is recommended. The aim of this study was to compare the safety and lipid-lowering efficacy of doubling the standard statin dose (STAT2) to that of co-administering ezetimibe 10 mg/day (EZE+statin) in Canadian patients at high CAD risk with persistent hyperlipidemia upon statin treatment.

Material and methods

Six-week, open-label, randomized, multicentre study. The primary outcome was the change in plasma LDL-C and secondary measures included the change in additional lipid parameters. Safety was assessed with the incidence of emergent adverse events (AEs).

Results

Eight hundred eighty-five patients (EZE+statin, n=586; STAT2, n=299) completed the study. The mean (SD) percent change in low-density lipoprotein cholesterol (LDL-C) was – 30.9% (18.2) for the EZE+statin group and –18.4% (19.0) for the STAT2 group (p=0.001). Percent and absolute decreases in total cholesterol (TC), triglycerides and the TC to high-density lipoprotein cholesterol ratio (TC/HDL-C) were significantly greater for the EZE+statin group (p = 0.001). After 6 weeks of treatment, 70% of the patients in the EZE+statin group and 48% of patients in the STAT2 group (OR=2.45, p<0.001) achieved target LDL-C levels of<2.5 mmol/l. Incidence of AEs was similar between groups, with the exception of a higher incidence of muscle disorders in the STAT2 group.

Conclusions

In patients at high CAD risk who are above the LDL-C target while on statin monotherapy, co-administration of ezetimibe is well tolerated and more effective in improving the lipid profile compared to doubling the existing statin dose.     

Psychiatric symptoms in dementia associated with stroke: a case-control analysis among predominantly African-American patients.

As part of a case-control study, the psychiatric symptoms and behavioral problems of 61 multi-infarct dementia (MID) cases and 86 multi-infarct controls without dementia were compared to determine the prevalence of psychiatric symptoms and to clarify psychiatric predictors of dementia associated with cerebral infarcts. Ninety-two percent of the cases and 85% of the controls were African American. Cases were generally older, less well educated, and had a greater number of strokes and more neurologic deficits than controls. The most frequent psychiatric symptoms as reported by caregivers of patients with MID were irritability (57.3%), apathy (44.4%), insomnia (43.6%), agitation (40.7%), impatience (37%), and emotional lability (28.3%). In multivariate analysis, apathy and irritability were independent predictors of dementia associated with cerebral infarcts unless tests of cognitive function were added to the model. Our findings suggest that psychiatric symptoms are common in African-American vascular dementia patients, and cognitive impairment may be associated with psychiatric symptoms, behavioral problems, and personality changes. As there is a paucity of information about the prevalence of psychiatric symptoms in African Americans with vascular dementia, additional studies are needed to validate these findings. A better understanding of psychiatric symptoms in vascular dementia could lead to improved diagnosis and treatment of this disorder.     

Additional benefit of lamivudine treatment as a preventive therapy for hepatic encephalopathy in patients with decompensated liver cirrhosis associated with hepatitis B

Lamivudine has previously been found to be effective not only in patients with compensated liver disease due to hepatitis B virus (HBV) but also in those with hepatic decompensation. However, long-term follow-up of patients with hepatic encephalopathy (HE) has not been previously reported. We describe a patient with recurrent HE associated with decompensated liver cirrhosis due to hepatitis B. After the initiation of treatment with lamivudine, manifestation of HE has not been observed for about 2 years and liver function has improved as well. This experience suggests that improved liver function using lamivudine may contribute to prevention from recurrence of HE.     

Coronary artery bypass grafting in patients with type 2 diabetes mellitus: a comparison between minimized and conventional extracorporeal circulation

Diabetes mellitus (DM) is an established independent risk factor for significant morbidity and mortality after coronary artery bypass grafting (CABG). The minimized extracorporeal circulation (MECC) allows a reduction of the negative effects associated with conventional extracorporeal circulation (CECC). In this study, the impact of the MECC on outcome of diabetic patients after CABG was assessed. Between January 2002 and December 2009, 1,184 patients with DM underwent elective isolated CABG using CECC (54.6%) or MECC (45.4%). All analysis was performed retrospectively. The extracorporeal circulation time was significantly reduced during MECC procedure. The postoperative increase of creatine kinase and lactate levels was significantly weaker in the MECC group (p < 0.001). Also, the transfusion requirements were significantly lower (p < 0.001). Furthermore, MECC patients had lower incidences of postoperative acute renal failure and sternal wound infections and shorter ICU and hospital lengths of stay (p < 0.05). Moreover, 30-day mortality was significantly reduced in the MECC group (p < 0.05). In conclusion, CABG surgery using MECC system is a safe alternative in patients with DM. A reduced postoperative mortality and lengths of stay, lower transfusion requirements, less renal and myocardial damage, and lower incidence of sternal wound infections encourage the usage of MECC system, especially in high-risk patients.     

Coronary artery bypass grafting in patients with low ejection fraction: the effect of intra-aortic balloon pump insertion on early outcome

Background: Survival benefit with intra-aortic balloon pump (IABP) insertion for coronary artery bypass grafting (CABG) patients with left ventricular dysfunction is controversial. The aim of this study was to assess the early results of CABG that predict 30-day mortality and prolonged length of hospital stay (LOS) after isolated CABG and the role of IABP application as a main predictor in patients with an ejection fraction (EF) of 30% or less. Materials and Methods: Eight hundred and thirty-three patients who underwent isolated CABG with EF 30% as the control group. Demographic and clinical characteristics and postoperative complications were considered. Data were analyzed using the student's t-test and chi-square test for univariate analysis and the analysis of covariance and logistic regression for multivariate analysis. Results: The thirty-day mortality rate (1.6% vs. 0.7%, P P P = 0.002) and prolonged LOS (P = 0.009). Also, urinary tract infection, prolonged ventilation, and renal failure as postoperative complications were statistically more in the group with the application of IABP. Conclusion: Low ejection fraction can positively affect thirty-day mortality and prolonged LOS and ICU stay in patients who undergo CABG. In these patients, IABP insertion is a strong predictor for early complication and mortality.     

Expression of let-7i is associated with Toll-like receptor 4 signal in coronary artery disease: effect of statins on let-7i and Toll-like receptor 4 signal

Toll-like receptor (TLR) 4 signal plays an important role in immunity in coronary artery disease (CAD). A recent report has demonstrated that one of the let-7 family microRNAs, let-7i, directly regulates Toll-like receptor 4 (TLR4) expression and contributes to immune response. The aim of this study was to determine whether let-7i is expressed with TLR4 in patients with CAD, and whether statins (atorvastatin or rosuvastatin) might affect these levels. To determine the effects of let-7i on TLR4 expression, human THP-1 cells transfected with let-7i were analyzed for TLR4 levels. This study included 98 patients with CAD and 48 subjects without CAD (non-CAD). Patients with CAD were randomized to 12 months of treatment with atorvastatin or rosuvastatin. Monocytes were obtained from peripheral blood at baseline and after 12 months of each type of therapy. Levels of let-7i and TLR4 were measured by real-time RT-PCR and FACS. Functional approaches to let-7i showed that transfection of let-7i into human THP-1 cells resulted in regulation of TLR4 expression. Levels of let-7i were lower in the CAD group than in the non-CAD group (0.98±0.42 vs. 4.65±1.21, P<0.01). There was a negative correlation between let-7i and TLR4 levels in patients with CAD (let-7i vs. TLR4 mRNA: r=-0.60, P<0.01; let-7i vs. TLR4 MFI: r=-0.32, P<0.01). The atorvastatin group had markedly increased let-7i levels and diminished TLR4 levels (all P<0.01), whereas the rosuvastatin group showed no change in these levels. This study suggests that atorvastatin down-regulates TLR4 signal via let-7i expression in CAD patients, possibly contributing to the beneficial effects of atorvastatin on let-7i-mediated TLR4 signal in this disorder.     

Severity of illness scoring systems in patients with bacteraemic pneumococcal pneumonia: implications for the intensive care unit care

Severity of illness scoring systems are useful for decisions on the management of patients with community-acquired pneumonia (CAP), including assessing the need for intensified therapy and monitoring, or for intensive care unit (ICU) admission. We compared the accuracy of the Pneumonia Severity Index (PSI), the CURB-65 and CRB-65 score, the modified-American Thoracic Society score (ATS), the IDSA/ATS guidelines and the Pitt Bacteraemia score (PBS) in evaluating severity of illness in 766 patients with bacteraemic pneumococcal pneumonia. We evaluated the sensitivity and specificity, the positive predictive value (PPV) and the negative predictive value (NPV) and the accuracy of the classification in predicting 14-day mortality. The PSI and the IDSA/ATS guidelines were the most sensitive whereas the PBS and modified-ATS scoring systems were the most specific in predicting mortality. The NPV was comparable for all four scoring systems (all above 90%), but the PPV was highest for PBS (54.2%) and lowest for PSI (23.2%). The predictive accuracy and discriminating power as measured by the receiver-operating characteristic (ROC) curve was highest for the PBS. Both the modified-ATS and the PBS scoring systems identified those patients who might benefit most from intensified care and monitoring. The PBS and modified-ATS proved superior to the IDSA/ATS guidelines, CURB-65 and CRB-65 with respect to their specificity and PPV. The low PPV of the PSI rendered it not usable as a parameter for decision-making in severely-ill patients with pneumococcal bacteraemia.     

Osteodysplastic primordial dwarfism: report of a further patient with manifestations similar to those seen in patients with types I and III

We describe a female infant with low birthweight osteodysplastic microcephalic dwarfism. The child has many manifestations in common with those seen in osteodysplastic primordial dwarfism types I and III. The classification of this heterogeneous group of disorders is discussed in the light of the above case.     

Radioimmunoassay for antibodies to human skeletal muscle myosin in serum from patients with polymyositis.

Antibodies to human skeletal muscle myosin were detected in 90% of sera from patients with polymyositis by radioimmunoassay using purified human myosin as antigen, and the mean titre was 4.24 X 10(-10)M. The incidence and the mean titre of anti-myosin antibodies were significantly higher than in patients without polymyositis. Anti-myosin antibody titres correlated with steroid therapy in polymyositis patients. Titres in untreated patients with polymyositis correlated with the severity of muscle weakness. Radioimmunoassay for anti-myosin antibodies should prove to be useful in the diagnosis of polymyositis and the evaluation of clinical state.