Archive for August, 2016

GRACE Score in Patients with COAD

Rothnie et al report on the performance of the GRACE score for acute coronary syndromes in patients with concomitant chronic obstructive airways disease (COAD or COPD). The data source was the Myocardial Ischemia National Audit Project (MINAP) registry. The authors found that the GRACE score underestimates the risk of acute coronary syndrome. Alternative models are explored (1.3 x GRACE estimate or MINAP registry derived GRACE). The authors also quantify the reclassification and discuss its implications.



To assess the accuracy of Global Registry of Acute Coronary Events (GRACE) scores in predicting mortality at 6 months for people with chronic obstructive
pulmonary disease (COPD) and to investigate how it might be improved.


Data were obtained on 481 849 patients with acute coronary syndrome admitted to UK hospitals between January 2003 and June 2013 from the Myocardial Ischaemia National Audit Project (MINAP) database. We compared risk of death between patients with COPD and those without COPD at 6 months,
adjusting for predicted risk of death. We then assessed whether several modifications improved the accuracy of the GRACE score for people with COPD.
Results The risk of death after adjusting for GRACE score predicted that risk of death was higher for patients with COPD than that for other patients (RR 1.29, 95% CI 1.28 to 1.33). Adding smoking into the GRACE score model did not improve accuracy for patients with COPD. Either adding COPD into the model (relative risk (RR) 1.00, 0.94 to 1.02) or multiplying the GRACE score by 1.3
resulted in better performance (RR 0.99, 0.96 to 1.01).


GRACE scores underestimate risk of death for people with COPD. A more accurate prediction of risk of death can be obtained by adding COPD into the GRACE score equation, or by multiplying the GRACE score predicted risk of death by 1.3 for people with COPD. This means that one third of patients with COPD currentlyclassified as low risk should be classified as moderate risk,
and could be considered for more aggressive early treatment after non-ST-segment elevation myocardial infarction or unstable angina.



Lower limit for LDL Target?

Leibowitz et al report a population based observational cohort study of patients with ischemic heart disease to try to quantify the dose (LDL achieved after 1 year statin therapy)-response(major adverse cardiac events included acute myocardial
infarction, unstable angina, stroke, angioplasty, bypass surgery, or all-cause mortality).

Propensity score matching was used and a sensitivity analysis of patient adherence was performed.



International guidelines recommend treatment with statins for patients with
preexisting ischemic heart disease to prevent additional cardiovascular events but differ
regarding target levels of low-density lipoprotein cholesterol (LDL-C). Trial data on this
question are inconclusive and observational data are lacking.


To assess the relationship between levels of LDL-C achieved with statin treatment
and cardiovascular events in adherent patients with preexisting ischemic heart disease.


Population-based observational cohort study from 2009 to 2013 using data from a health care organization in Israel covering more than 4.3 million members. Included patients had ischemic heart disease, were aged 30 to 84 years, were treated with statins, and were at least 80% adherent to treatment or, in a sensitivity analysis, at least 50% adherent. Patients with active cancer or metabolic abnormalities were excluded.


Index LDL-C was defined as the first achieved serum LDL-C measure after at
least 1 year of statin treatment, grouped as low (70.0mg/dL), moderate (70.1-100.0
mg/dL), or high (100.1-130.0mg/dL).


Major adverse cardiac events included acutemyocardial
infarction, unstable angina, stroke, angioplasty, bypass surgery, or all-cause mortality. The
hazard ratio of adverse outcomes was estimated using 2 Cox proportional hazards models
with low vs moderate and moderate vs high LDL-C, adjusted for confounders and further
tested using propensity score matching analysis.


The cohort with at least 80% adherence included 31 619 patients, for whom the
mean (SD) age was 67.3 (9.8) years. Of this population, 27%were female and 29% had low,
53%moderate, and 18%high LDL-C when taking statin treatment. Overall, there were 9035
patients who had an adverse outcome during a mean 1.6 years of follow-up (6.7 per 1000
persons per year). The adjusted incidence of adverse outcomes was not different between
low and moderate LDL-C (hazard ratio [HR], 1.02; 95%CI, 0.97-1.07; P = .54), but it was lower
with moderate vs high LDL-C (HR, 0.89; 95%CI, 0.84-0.94; P < .001). Among 54 884
patients with at least 50% statin adherence, the adjusted HR was 1.06 (95%CI, 1.02-1.10;
P = .001) in the low vs moderate groups and 0.87 (95%CI, 0.84-0.91; P = .001) in the
moderate vs high groups.


Patients with LDL-C levels of 70 to 100mg/dL taking statins
had lower risk of adverse cardiac outcomes compared with those with LDL-C levels between
100 and 130mg/dL, but no additional benefit was gained by achieving LDL-C of 70mg/dL or
less. These population-based data do not support treatment guidelines recommending very
low target LDL-C levels for all patients with preexisting heart disease.



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Effective Age

Professor Spiegelhalter reports a useful way of presenting impact of lifestyle risk factor. He explains the concept of effective age. This takes the hazard of risk factor and finds the age that corresponds to that risk in healthy person. This is your effective age. Professor Spiegelhalter shows how easily this can be estimated using plausible assumptions underlying Cox proportional hazard models.


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Astronauts and Cardiovascular Disease

Delp et al report on the mortality rate  among three groups of astronauts: no orbital mission, low earth mission, Apollo lunar mission. The authors found a high rate of cardiovascular mortality for the Apollo astronauts. The authors then performed functional and protein expression studies on the gastrocnemius feeding arteries and coronary arteries  of mice 6 to 7 months after simulation of “weightlessness”, radiation and both versus a control group. Vasodilator responses to Acetyl Choline were significantly impaired in both active groups, vasoconstriction was not significantly different. Xanthine oxidase expression was raised in the intervention groups. The authors  suggest these findings have important implications for human deep space exploration.


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Body Mass Index: A Complex Story. Monozygotic Twin Study

Nordström et al report  of 4046 monozygotic twins with discordant body mass indexes identified from a Swedish twin registry. The study recruitment was between 1998 and 2003 and follow up to December 2013. The primary end-point was the composite of death and myocardial infarction.

The abstract follows:


Observational studies have shown that obesity is a major risk factor for
cardiovascular disease and death. The extent of genetic confounding in these associations
is unclear.


To compare the risk ofmyocardial infarction (MI), type 2 diabetes, and death
in monozygotic (MZ) twin pairs discordant for body mass index (BMI).


A cohort of 4046 MZ twin pairs with discordant BMIs
(difference >0.01) was identified using the nationwide Swedish twin registry. The study was
conducted from March 17, 1998, to January 16, 2003, with follow-up regarding incident
outcomes until December 31, 2013.


The combined primary end point of death or MI and the
secondary end point of incident diabetes were evaluated in heavier compared with leaner
twins in a co-twin control analysis using multivariable conditional logistic regression.


Mean (SD) baseline age for both cohorts was 57.6 (9.5) years (range, 41.9-91.8
years). During a mean follow-up period of 12.4 (2.5) years, 203 MIs (5.0%) and 550 deaths
(13.6%) occurred among heavier twins (mean [SD] BMI, 25.9 [3.6] [calculated as weight in
kilograms divided by height in meters squared]) compared with 209 MIs (5.2%) and 633
deaths (15.6%) among leaner twins (mean [SD] BMI, 23.9 [3.1]; combined multivariable
adjusted odds ratio [OR], 0.75; 95%CI, 0.63-0.91). Even in twin pairs with BMI discordance
of 7.0 or more (mean [SE], 9.3 [0.7]), where the heavier twin had a BMI of 30.0 or more
(n = 65 pairs), the risk of MI or death was not greater in heavier twins (OR, 0.42; 95%CI,
0.15-1.18). In contrast, in the total cohort of twins, the risk of incident diabetes was greater
in heavier twins (OR, 2.14; 95%CI, 1.61-2.84). Finally, increases in BMI since 30 years before
baseline were not associated with the later risk of MI or death (OR, 0.97; 95%CI, 0.89-1.05)
but were associated with the risk of incident diabetes (OR, 1.13; 95%CI, 1.01-1.26).


In MZ twin pairs, higher BMI was not associated with an
increased risk of MI or death but was associated with the onset of diabetes. These results may
suggest that lifestyle interventions to reduce obesity are more effective in decreasing the risk
of diabetes than the risk of cardiovascular disease or death.
JAMA Intern

Supplemental material is available here.


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CSANZ Acute Coronary Syndrome Guidelines 2016

The CSANZ guidelines for acute coronary syndromes have been released. Extract of the key recommendations follow.


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