[show abstract][hide abstract] ABSTRACT: BACKGROUND: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.
[show abstract][hide abstract] ABSTRACT: OBJECTIVES
To evaluate the effects of insulin glargine and n-3 polyunsaturated fatty acid (n-3FA) supplements on carotid intima-media thickness (CIMT).RESEARCH DESIGN AND METHODS
We enrolled 1,184 people with cardiovascular (CV) disease and/or CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or early type 2 diabetes in a randomized multicenter 2 × 2 factorial design trial. Participants received open-label insulin glargine (targeting fasting glucose levels ≤5.3 mmol/L [95 mg/dL]) or standard glycemic care and double-blind therapy with a 1-g capsule of n-3FA or placebo. The primary trial outcome was the annualized rate of change in maximum CIMT for the common carotid, bifurcation, and internal carotid artery segments. Secondary outcomes were the annualized rates of change in maximum CIMT for the common carotid and the common carotid plus bifurcation, respectively. Baseline followed by annual ultrasounds were obtained during a median follow-up of 4.9 years.RESULTSCompared with standard care, insulin glargine reduced the primary CIMT outcome, but the difference was not statistically significant (difference = 0.0030 ± 0.0021 mm/year; P = 0.145) and significantly reduced the secondary CIMT outcomes (differences of 0.0033 ± 0.0017 mm/year [P = 0.049] and 0.0045 ± 0.0021 mm/year [P = 0.032], respectively). There were no differences in the primary and secondary outcomes between the n-3FA supplement and placebo groups.CONCLUSIONS
In people with CV disease and/or CV risk factors and dysglycemia, insulin glargine used to target normoglycemia modestly reduced CIMT progression, whereas daily supplementation with n-3FA had no effect on CIMT progression.
[show abstract][hide abstract] ABSTRACT: Patients with increased numbers of cholesterol-depleted apolipoprotein B (apoB) particles frequently have multiple other abnormalities, which might confound the comparison of apoB and non-high-density-lipoprotein-cholesterol (non-HDL-C) as markers of cardiovascular risk.
We wanted to determine whether the superiority of apoB over non-HDL-C as a marker of cardiovascular risk in the INTERHEART study is due to such variables that act as confounders of the primary comparison.
To test for confounding, cases and controls were first separated into 3 groups on the basis of the percentile levels within the study of non-HDL-C and apoB with discordance defined as a difference of 5 percentile points. Logistic regression was used to compute odds ratio of myocardial infarction (as an outcome) for different categories, assuming concordance as reference adjusted for other confounders.
Plasma triglyceride and non-HDL-C levels were highest in the discordant group with lowest risk and lowest in the discordant group with highest risk, whereas apoB was highest in the discordant group with the highest risk and lowest in the discordant group with the lowest group. Moreover, no significant change was found in the odds ratio for either discordant group when adjusted for the effect of any of the variables examined, evidence that none confounded the primary comparison.
Factors such as hypertriglyceridemia do not confound the comparison of apoB and non-HDL-C, further evidence that apoB is superior to non-HDL-C as a marker of the importance of the apoB atherogenic lipoproteins in cardiovascular risk.
Journal of Clinical Lipidology 01/2013; 7(6):626-31. · 2.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: The influence of multiple maternal and pregnancy characteristics on offspring cardiometabolic traits at birth is not well understood and was evaluated in this study.
The Family Atherosclerosis Monitoring In earLY life (FAMILY) Study prospectively evaluated 11 cardiometabolic traits in 901 babies born to 857 mothers. The influence of maternal age, health (pre-pregnancy weight, blood pressure, glycemic status, lipids), health behaviors (diet, activity, smoking) and pregnancy characteristics (gestational age at birth, gestational weight gain and placental-fetal ratio) were examined. Greater gestational age influenced multiple newborn cardiometabolic traits including cord blood lipids, glucose and insulin, body fat and blood pressure. In a subset of 442 singleton mother/infant pairs, principal component analysis grouped 11 newborn cardiometabolic traits into 5 components (anthropometry/insulin, 2 lipid components, blood pressure and glycemia), accounting for 74% of the variance of the 11 outcome variables. Determinants of these components, corrected for sex and gestational age, were examined. Baby anthropometry/insulin was independently predicted by higher maternal pre-pregnancy weight (standardized estimate 0.30) and gestational weight gain (0.30; both p<0.0001) and was inversely related to smoking during pregnancy (-0.144; p = 0.01) and maternal polyunsaturated to saturated fat intake (-0.135;p = 0.01). Component 2 (HDL-C/Apo Apolipoprotein1) was inversely associated with maternal age. Component 3 (blood pressure) was not clustered with any other newborn cardiometabolic trait and no associations with maternal pregnancy characteristics were identified. Component 4 (triglycerides) was positively associated with maternal hypertension and triglycerides, and inversely associated with maternal HDL and age. Component 5 (glycemia) was inversely associated with placental/fetal ratio (-0.141; p = 0.005). LDL-C was a bridging variable between the lipid factors and glycemia.
Maternal health, health behaviours and placenta to fetal weight ratio are associated with newborn cardiometabolic traits over and above gestational age. Future investigations are needed to determine if these factors remain important determinants of cardiometabolic health throughout childhood.
PLoS ONE 01/2013; 8(2):e55815. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: Apolipoproteins B (apoB) and A1 (apoA1) may be better markers of atherosclerosis than serum lipids. We used computational methods to estimate apoB and apoA1 from serum total cholesterol, HDL-cholesterol and triglycerides and tested their clinical value in comparison to measured apoB and apoA1 values. METHODS: ApoB and apoA1 were measured with standard methods and estimated based on neural network regression models in 2166 young adult with data on carotid artery intima-media thickness (cIMT). RESULTS: Correlations between estimated and measured apoB and apoA1 were r = 0.98 and r = 0.95, respectively. ApoB/apoA1-ratio (both measured and estimated) associated with cIMT in multivariable models, and predicted cIMT at all levels of LDL-cholesterol concentration. Strong correlations between the estimated apolipoproteins and those measured from fasting samples were replicated in over 15,000 Caucasian subjects (r = 0.93-0.96 for apoB and r = 0.91-0.92 for apoA1). Correlations with cIMT were replicated in over 2000 individuals. Estimated apoB/apoA1-ratio calculated from non-fasting lipids in over 20,000 individuals in the INTERHEART study was better than any of the cholesterol measures for estimation of the myocardial risk. CONCLUSIONS: Serum cholesterol, HDL-cholesterol and triglycerides can be used to compute clinically useful estimates of apoB and apoA1. Using this methodology, estimates of apolipoproteins could be routinely added to laboratory reports to complement lipoprotein lipids in risk assessment.
[show abstract][hide abstract] ABSTRACT: OBJECTIVES: Previous work on high-sensitivity troponin I (hs-cTnI) has demonstrated that it may identify patients with stable cardiovascular disease (CVD) at risk for future myocardial infarction (MI). In this study, we assessed if hs-cTnT concentrations could also identify those stable CVD patients at high risk for future MI and other ischemic cardiac outcomes. METHODS: hs-cTnT (lot:153-401) was measured in specimens obtained at randomisation in the Heart Outcomes Prevention Evaluation (HOPE) study (n=2941 stable CVD patients, 4.5years follow-up). The primary outcome for the HOPE study (MI, stroke, or cardiovascular death) was used to identify cutoffs by receiver operator characteristic (ROC) curve analysis and was used in conjugation with the 95th and 99th percentile upper limits to construct different concentration ranges, which were assessed using log-rank tests and multivariable Cox proportional hazard models. These different concentration ranges were then assessed for the components of the primary outcome and for heart failure (HF). RESULTS: The ROC derived hs-cTnT cutoff was 8ng/L for the primary outcome. Subjects with hs-cTnT either below (8 to <14ng/L) or slightly above the published 99th from a healthy population (14 to 21ng/L) had similar probability for the primary outcome. Those with hs-cTnT concentrations >31ng/L had the highest probability and greatest risk for future MI, HF, and cardiovascular death as compared to those with hs-cTnT concentrations <8ng/L. CONCLUSION: In patients with stable CVD disease hs-cTnT measurement identifies those at risk for MI as well as HF and cardiovascular death.
[show abstract][hide abstract] ABSTRACT: OBJECTIVES: Whether non-HDL-C and apoB are equivalent markers of cardiovascular risk remains controversial. Only when apoB particles in toto contain either more or less cholesterol than normal - that is, when their composition is discordant - could apoB and non-HDL-C predict risk differently. Accordingly, this study tests within the INTERHEART data base whether apoB or non-HDL-C are equivalent markers of risk when the two markers are discordant. METHODS: The INTERHEART study is a standardized case-control study of acute myocardial infarction with blood samples in 9345 cases and 12,120 controls from 52 countries. To produce comparability, the concentrations of non-HDL-C and apoB are expressed as percentiles (P) within the study population. Concordance is defined as the phenotype when P Non-HDL-C = P apoB (that is, apoB particles contain a normal mass of cholesterol). Discordance is defined either as the phenotype when P Non-HDL-C > P apoB (cholesterol-enriched apoB particles) or P Non-HDL-C < P apoB (cholesterol-depleted apoB particles). The OR of cases to controls was determined for both discordant groups and compared to the ratio of cases to controls in the concordant group, which was the reference group. An OR > 1 means that risk is greater in the discordant than in the reference phenotype whereas an OR < 1 means the cases are less common in the discordant phenotype than in the reference group. RESULTS: When discordance was defined as percentiles within 5%, a definition that produced equal numbers of discordant and concordant individuals, the OR for P Non-HDL-C > apoB (cholesterol-enriched apoB particles) was 0.72 (0.67-0.77 95% CI) indicating risk was less than the reference concordant group whereas the OR for P Non-HDL-C < apoB (cholesterol-depleted apoB particles) was 1.58 (1.38-1.58 95% CI) indicating risk was significantly greater than the reference concordant group. The same findings were reproduced using all definitions of discordance from 1% to 10%. Moreover, the pattern of findings was consistent amongst the ethnic groups that made up the overall study population. CONCLUSION: Discordance analysis demonstrates that apoB is a more accurate marker of cardiovascular risk than non-HDL-C.
[show abstract][hide abstract] ABSTRACT: Of the 200 million adults worldwide who undergo noncardiac surgery each year, more than 1 million will die within 30 days.
To determine the relationship between the peak fourth-generation troponin T (TnT) measurement in the first 3 days after noncardiac surgery and 30-day mortality.
A prospective, international cohort study that enrolled patients from August 6, 2007, to January 11, 2011. Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery.
Patients' TnT levels were measured 6 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery, and the independent variables included 24 preoperative variables. We repeated this analysis, adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients' risk of death.
A total of 15,133 patients were included in this study. The 30-day mortality rate was 1.9% (95% CI, 1.7%-2.1%). Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL, occurring in 11.6% of patients, were associated with higher 30-day mortality compared with the reference group (peak TnT ≤ 0.01 ng/mL): peak TnT of 0.02 ng/mL (adjusted hazard ratio [aHR], 2.41; 95% CI, 1.33-3.77); 0.03 to 0.29 ng/mL (aHR, 5.00; 95% CI, 3.72-6.76); and 0.30 ng/mL or greater (aHR, 10.48; 95% CI, 6.25-16.62). Patients with a peak TnT value of 0.01 ng/mL or less, 0.02, 0.03-0.29, and 0.30 or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively. Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without (C index = 0.85 vs 0.81; difference, 0.4; 95% CI, 0.2-0.5; P < .001 for difference between C index values). The net reclassification improvement with TnT was 25.0% (P < .001).
Among patients undergoing noncardiac surgery, the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality.
JAMA The Journal of the American Medical Association 06/2012; 307(21):2295-304. · 29.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators W ORLDWIDE, MORE THAN 200 million adults have major noncardiac sur-gery annually. 1,2 Despite benefits associated with surgery, major perioperative complications, including death, occur. 3 More than 1 million adults worldwide will die within 30 days of non-cardiac surgery each year. 1,2 Perioperative risk estimation identi-fies patients who require more inten-sive monitoring and management in the postoperative period. Current preopera-tive risk prediction models for 30-day mortality have limitations. 4,5 Some cli-nicians advocate monitoring troponin measurements after vascular surgery, 6 and inconclusive evidence suggests that troponin measurements after abdomi-nal aortic surgery may enhance predic-tion of short-term mortality. 7 Little is known about optimal troponin thresh-old(s) for predicting mortality after non-cardiac surgery. A large international study called the VISION Study (Vascular Events in Noncardiac Surgery Patients Cohort Evaluation; clinicaltrials.gov identifier, NCT00512109) is evaluat-ing major complications after noncar-diac surgery. Participating patients have troponin T (TnT) levels measured after noncardiac surgery. We assessed the relationship between the peak fourth-generation TnT measurement after noncardiac surgery and 30-day mortality. METHODS Study Design and Eligibility Criteria The VISION Study is a prospective co-hort study of a representative sample of patients undergoing noncardiac sur-gery. VISION was designed to recruit 40 000 patients in North and South America, Africa, Asia, Australia, and Eu-rope to evaluate major complications after noncardiac surgery. At the begin-ning of this study, patients had fourth-generation TnT measurements after noncardiac surgery. The first 15 000 pa- Context Of the 200 million adults worldwide who undergo noncardiac surgery each year, more than 1 million will die within 30 days.
JAMA The Journal of the American Medical Association 06/2012; 307(21-21):2295. · 29.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: The precise relationship between sodium and potassium intake and cardiovascular (CV) risk remains uncertain, especially in patients with CV disease.
To determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and CV events in patients with established CV disease or diabetes mellitus.
Observational analyses of 2 cohorts (N = 28,880) included in the ONTARGET and TRANSCEND trials (November 2001-March 2008 from initial recruitment to final follow-up). We estimated 24-hour urinary sodium and potassium excretion from a morning fasting urine sample (Kawasaki formula). We used restricted cubic spline plots to describe the association between sodium and potassium excretion and CV events and mortality, and to identify reference categories for sodium and potassium excretion. We used Cox proportional hazards multivariable models to determine the association of urinary sodium and potassium with CV events and mortality.
CV death, myocardial infarction (MI), stroke, and hospitalization for congestive heart failure (CHF).
At baseline, the mean (SD) estimated 24-hour excretion for sodium was 4.77 g (1.61); and for potassium was 2.19 g (0.57). After a median follow-up of 56 months, the composite outcome occurred in 4729 (16.4%) participants, including 2057 CV deaths, 1412 with MI, 1282 with stroke, and 1213 with hospitalization for CHF. Compared with the reference group with estimated baseline sodium excretion of 4 to 5.99 g per day (n = 14,156; 6.3% participants with CV death, 4.6% with MI, 4.2% with stroke, and 3.8% admitted to hospital with CHF), higher baseline sodium excretion was associated with an increased risk of CV death (9.7% for 7-8 g/day; hazard ratio [HR], 1.53; 95% CI, 1.26-1.86; and 11.2% for >8 g/day; HR, 1.66; 95% CI, 1.31-2.10), MI (6.8%; HR, 1.48; 95% CI, 1.11-1.98 for >8 g/day), stroke (6.6%; HR, 1.48; 95% CI, 1.09-2.01 for >8 g/day), and hospitalization for CHF (6.5%; HR, 1.51; 1.12-2.05 for >8 g/day). Lower sodium excretion was associated with an increased risk of CV death (8.6%; HR, 1.19; 95% CI, 1.02-1.39 for 2-2.99 g/day; 10.6%; HR, 1.37; 95% CI, 1.09-1.73 for <2 g/day), and hospitalization for CHF (5.2%; HR, 1.23; 95% CI, 1.01-1.49 for 2-2.99 g/day) on multivariable analysis. Compared with an estimated potassium excretion of less than 1.5 g per day (n = 2194; 6.2% with stroke), higher potassium excretion was associated with a reduced risk of stroke (4.7% [HR, 0.77; 95% CI, 0.63-0.94] for 1.5-1.99 g/day; 4.3% [HR, 0.73; 95% CI, 0.59-0.90] for 2-2.49 g/day; 3.9% [HR, 0.71; 95% CI, 0.56-0.91] for 2.5-3 g/day; and 3.5% [HR, 0.68; 95% CI, 0.49-0.92] for >3 g/day) on multivariable analysis.
The association between estimated sodium excretion and CV events was J-shaped. Compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all CV events, and a sodium excretion of less than 3 g per day was associated with increased risk of CV mortality and hospitalization for CHF. Higher estimated potassium excretion was associated with a reduced risk of stroke.
JAMA The Journal of the American Medical Association 11/2011; 306(20):2229-38. · 29.98 Impact Factor