Archive for June, 2016

Aspirin Primary Prevention

Mora et al present a viewpoint on personalizing use of aspirin in primary prevention.

The supplement is available here.


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Lisinopril and Incidence of Conduction System Disease (ALLHAT)

Dewland et al present an interesting paper examining the relationship between Lisinopril and incidence of conduction system disease in patients enrolled in the ALLHAT trial.



Cardiac conduction abnormalities are associated with an increased risk for morbidity and mortality, and understanding factors that accelerate or delay conduction system disease could help to identify preventive and therapeutic strategies. Antifibrotic and anti-inflammatory properties of angiotensin-converting enzyme inhibitors and treatment for hyperlipidemia may reduce the risk for incident conduction system disease.


To identify the effect of pharmacologic therapy randomization and clinical risk
factors on the incidence of conduction system disease.


This secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigation acquired data from 623 North American centers. A total of 21 004 ambulatory individuals 55 years or older with hypertension and at least 1 other cardiac risk factor were included in the analysis.


Participants were randomly assigned to receive amlodipine besylate, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin sodium vs usual care.
MAIN OUTCOMES AND MEASURES An electrocardiogram (ECG)was obtained at study enrollment and every 2 years of follow-up. The development of incident first-degree atrioventricular block, left anterior fascicular block, incomplete left bundle branch block (LBBB), LBBB, incomplete right bundle branch block (RBBB), RBBB, or intraventricular
conduction delay was assessed by serial ECGs.


The 21 004 participants (11 758 men [56.0%]; 9246 women [44.0%]; mean [SD] age, 66.5 [7.3] years) underwent a mean (SD) follow-up of 5.0 (1.2) years. Among the 1114 participants who developed any conduction defect, 389 developed LBBB, 570 developed RBBB, and 155 developed intraventricular conduction delay. Compared with chlorthalidone,
randomization to lisinopril was associated with a significant 19% reduction in conduction abnormalities (hazard ratio [HR], 0.81; 95%CI, 0.69-0.95; P = .01). Treatment with amlodipine, however, was not associated with a significant difference in conduction outcome events (HR, 0.94; 95%CI, 0.81-1.09; P = .42). Similarly, pravastatin treatment was not associated with a reduced adjusted risk for incident disease compared with usual hyperlipidemia treatment (HR, 1.13; 95%CI, 0.95-1.35; P = .18). Increased age (HR, 1.47; 95% CI, 1.34-1.63; P < .001), male sex (HR, 0.59; 95%CI, 0.50-0.73; P < .001), white race (HR, 0.59; 95%CI, 0.50-0.70; P < .001), diabetes (HR, 1.23; 95%CI, 1.07-1.42; P = .003), and left ventricular hypertrophy (HR, 3.20; 95%CI, 2.61-3.94; P < .001) were also independently associated with increased risk for conduction system disease.


Incident conduction system disease is significantly reduced by lisinopril therapy and is independently associated with multiple clinical factors. Further studies are warranted to determine whether pharmacologic treatment affects conduction abnormality outcomes, including pacemaker implantation.


Body Mass Index in Adolescence and Long term Cardiovascular Mortality

Twig et al report a longitudinal study of 2.3 million Israeli adolescents from 1967 to 2010. Body mass index regarded as normal (50th to 74th percentile) was associated with higher long term cardiovascular mortality (reference group 5th to 24th percentile).



In light of the worldwide increase in childhood obesity, we examined the association between body-mass index (BMI) in late adolescence and death from cardiovascular causes in adulthood.


We grouped data on BMI, as measured from 1967 through 2010 in 2.3 million
Israeli adolescents (mean age, 17.3±0.4 years), according to age- and sex-specific percentiles from the U.S. Centers for Disease Control and Prevention. Primary outcomes were the number of deaths attributed to coronary heart disease, stroke, sudden death from an unknown cause, or a combination of all three categories (total cardiovascular causes) by mid-2011. Cox proportional-hazards models were used.


During 42,297,007 person-years of follow-up, 2918 of 32,127 deaths (9.1%) were
from cardiovascular causes, including 1497 from coronary heart disease, 528 from
stroke, and 893 from sudden death. On multivariable analysis, there was a graded
increase in the risk of death from cardiovascular causes and all causes that started among participants in the group that was in the 50th to 74th percentiles of BMI (i.e., within the accepted normal range). Hazard ratios in the obese group (≥95th percentile for BMI), as compared with the reference group in the 5th to 24th percentiles, were 4.9 (95% confidence interval [CI], 3.9 to 6.1) for death from coronary heart disease, 2.6 (95% CI, 1.7 to 4.1) for death from stroke, 2.1 (95% CI, 1.5 to 2.9) for sudden death, and 3.5 (95% CI, 2.9 to 4.1) for death from total cardiovascular
causes, after adjustment for sex, age, birth year, sociodemographic characteristics,and height. Hazard ratios for death from cardiovascular causes in the same percentile groups increased from 2.0 (95% CI, 1.1 to 3.9) during follow-up for 0 to 10 years to 4.1 (95% CI, 3.1 to 5.4) during follow-up for 30 to 40 years; during both periods, hazard ratios were consistently high for death from coronary heart disease. Findings persisted in extensive sensitivity analyses.
A BMI in the 50th to 74th percentiles, within the accepted normal range, during adolescence was associated with increased cardiovascular and all-cause mortality during 40 years of follow-up. Overweight and obesity were strongly associated with increased cardiovascular mortality in adulthood.



Genetic testing in children and young adults with Sudden Cardiac Death

Bagnall et al report a prospective study of sudden cardiac death in children and young adults. The use of genetic testing for unexplained cases is described.



Sudden cardiac death among children and young adults is a devastating event. We
performed a prospective, population-based, clinical and genetic study of sudden
cardiac death among children and young adults.


We prospectively collected clinical, demographic, and autopsy information on all
cases of sudden cardiac death among children and young adults 1 to 35 years of
age in Australia and New Zealand from 2010 through 2012. In cases that had no
cause identified after a comprehensive autopsy that included toxicologic and histologic
studies (unexplained sudden cardiac death), at least 59 cardiac genes were
analyzed for a clinically relevant cardiac gene mutation.


A total of 490 cases of sudden cardiac death were identified. The annual incidence
was 1.3 cases per 100,000 persons 1 to 35 years of age; 72% of the cases involved
boys or young men. Persons 31 to 35 years of age had the highest incidence of
sudden cardiac death (3.2 cases per 100,000 persons per year), and persons 16 to
20 years of age had the highest incidence of unexplained sudden cardiac death
(0.8 cases per 100,000 persons per year). The most common explained causes of
sudden cardiac death were coronary artery disease (24% of cases) and inherited
cardiomyopathies (16% of cases). Unexplained sudden cardiac death (40% of cases)
was the predominant finding among persons in all age groups, except for those
31 to 35 years of age, for whom coronary artery disease was the most common
finding. Younger age and death at night were independently associated with unexplained
sudden cardiac death as compared with explained sudden cardiac death.
A clinically relevant cardiac gene mutation was identified in 31 of 113 cases (27%)
of unexplained sudden cardiac death in which genetic testing was performed. During
follow-up, a clinical diagnosis of an inherited cardiovascular disease was
identified in 13% of the families in which an unexplained sudden cardiac death


The addition of genetic testing to autopsy investigation substantially increased the
identification of a possible cause of sudden cardiac death among children and
young adults.


NB: look at genetic findings





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Nature Disease Primer on Aortic Stenosis

Lindman et al provide an excellent primer on aortic stenosis including epidemiology, pathophysiology, diagnosis and assessment of severity and management including the evidence for TAVR and the different approaches (note the file size ~ 15 Mb).

Some excerpts follow:












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Obesity and Early Complications After Coronary Artery Bypass Surgery

Terada et al report on the relationship between obesity and complications post coronary artery bypass surgery in retrospective single centre study using patients from APPROACH registry. Mortality was not related to obesity. Infection and length of stay was correlated with obesity.



Better understanding of the relationship between obesity and postsurgical adverse outcomes is needed to provide quality and efficient care. We examined the relationship of obesity with the incidence of early adverse outcomes and in-hospital
length of stay following coronary artery bypass grafting surgery.

Methods and Results

We analyzed data from 7560 patients who underwent coronary artery bypass grafting. Using body mass index (BMI; in kg/m2) of 18.5 to 24.9 as a reference, the associations of 4 BMI categories (25.0–29.9, 30.0–34.9, 35.0–39.9, and ≥40.0) with rates of operative mortality, overall early complications, subgroups of early complications (ie, infection, renal and pulmonary complications), and length of stay were assessed while adjusting for clinical covariates. There was no difference in operative mortality;
however, higher risks of overall complications were observed for patients with BMI 35.0 to 39.9 (adjusted odds ratio 1.35, 95% CI (1.11–1.63) and ≥40.0 (adjusted odds ratio 1.56, 95% CI 1.21–2.01). Subgroup analyses identified obesity as an independent risk factor for infection (BMI 30.0–34.9: adjusted odds ratio 1.60, 95% CI 1.24–2.05; BMI 35.0–39.9: adjusted odds ratio 2.34, 95% CI( 1.73–3.17); BMI ≥40.0: adjusted odds ratio 3.29, 95% CI 2.30–4.71). Median length of stay was longer with BMI ≥40.0 than with BMI
18.5 to 24.9 (median 7.0 days [interquartile range 5 to 10] versus 6.0 days [interquartile range 5 to 9], P=0.026).


BMI ≥40.0 was an independent risk factor for longer length of stay, and infection was a potentially modifiable risk factor. Greater perioperative attention and intervention to control the risks associated with infection and length of stay in patients with BMI ≥40.0 may improve patient care quality and efficiency.


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Longitudinal Troponin T Changes Predictors of Mortality, Coronary Heart Disease and Heart Failure

McEvoy et al report a six year community prospective observational study assessing the relationship between changes in high-sensitivity troponin T and cardiovascular events (coronary heart disease, heart failure) and mortality.



High-sensitivity cardiac troponin T (hs-cTnT) is a biomarker of cardiovascular risk and could be approved in the United States for clinical use soon. However, data linking long-term temporal change in hs-cTnT to outcomes are limited, particularly in primary prevention settings.


To examine the association of 6-year change in hs-cTnT with incident coronary heart disease (CHD), heart failure (HF), and all-cause mortality.


This prospective observational cohort study, performed from January 1, 1990, to December 31, 2011, included 8838 participants with biracial representation from the Atherosclerosis Risk in Communities Study who were initially free of
CHD and HF and who had hs-cTnT measured twice, 6 years apart. Data analysis was performed from October 28, 2014, to March 9, 2016.


Risk factor and temporal hs-cTnT datawere collected. Using Cox proportional hazards regression, we examined the association of hs-cTnT change with subsequent CHD, HF, and death during a maximum of 16 years. Improvement in
discrimination was determined by the Harrell C statistic.


Of the 8838 participants (mean age, 56 years; 5215 female [59.0%]; 1891 black [21.4%]) there were 1157 CHD events, 965 HF events, and 1813 deaths overall. Incident detectable hs-cTnT (baseline, <0.005 ng/mL; follow-up,0.005 ng/mL) was independently associated with subsequent CHD (hazard ratio [HR], 1.4; 95%CI, 1.2-1.6), HF (HR, 2.0; 95%CI, 1.6-2.4), and death (HR, 1.5; 95%CI, 1.3-1.7), relative to an hs-cTnT level less than 0.005 ng/mL at both visits. In addition, HRs as high as 4 for CHD and death and 8 for HF were recorded among individuals with the most marked hs-cTnT increases (eg, baseline, < 0.005 ng/mL; follow-up,0.014 ng/mL). Risk for subsequent outcomes was lower among those with relative hs-cTnT reductions greater than 50% from baseline. Furthermore, information on hs-cTnT change improved discrimination for HF and death when added to a model that included traditional risk factors, N-terminal pro–brain natriuretic peptide, and baseline
hs-cTnT level. Among individuals with adjudicated HF hospitalizations, hs-cTnT change appeared to be similarly associated with HF with reduced and preserved ejection fraction.


Temporal increases in hs-cTnT, suggestive of progressive myocardial damage, are independently associated with incident CHD, death, and, above all, HF. Serial determination of hs-cTnT trajectory adds clinically relevant information to baseline
testing and may be useful in prognostic assessments and the targeting of prevention strategies to high-risk individuals, especially among persons with stage A or B HF.

The editorial is available here.