Serial evaluation of electrocardiographic left ventricular hypertrophy for prediction of risk in hypertensive patients

Background

Although the presence and severity of electrocardiographic (ECG) left ventricular hypertrophy (LVH) have been associated with an increased risk of cardiovascular (CV) morbidity and mortality, the relationship of regression of ECG LVH during antihypertensive therapy to CV risk has only recently been examined.

Methods

Electrocardiographic LVH was evaluated over time in 9193 hypertensive patients enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension study. Patients were treated with losartan- or atenolol-based regimens and followed with serial ECGs at 6 months and then yearly until death or study end. Electrocardiographic LVH was measured using gender-adjusted Cornell product (RaVL + SV3 [+6 mm in women]) ? QRS duration) and Sokolow-Lyon voltage (SV1 + RV5/6).

Results

After mean (SD) follow-up of 4.8 (0.9) years, the Losartan Intervention for Endpoint Reduction in Hypertension study composite end point of CV death, nonfatal myocardial infarction, or stroke occurred in 1096 patients. In Cox regression models controlling for treatment type, baseline Framingham risk score, baseline, and in-treatment blood pressure and for severity of baseline ECG LVH by Cornell product and Sokolow-Lyon voltage, lower in-treatment ECG LVH by Cornell product and Sokolow-Lyon voltage were associated with 14% and 17% lower rates, respectively, of the composite CV end point: adjusted hazard ratios (HRs) of 0.86 (95% confidence interval [CI], 0.82-0.90; P < .001) for every 1050 mm · ms (1 SD) decrease in Cornell product and 0.83 (95% CI, 0.78-0.88; P < .001) for every 10.5 mm (1 SD) decrease in Sokolow-Lyon voltage. In parallel analyses, lower Cornell product and Sokolow- Lyon voltage were each independently associated with lower risks of CV mortality (HR, 0.78; 95% CI, 0.73-0.83; P < .001; HR, 0.80; 95% CI, 0.73-0.87; P < .001), of myocardial infarction (HR, 0.90; 95% CI, 0.82-0.98; P = .011; HR, 0.90; 95% CI, 0.81-1.00; P = .043), and of stroke (HR, 0.90; 95% CI, 0.84-0.96; P = .002; HR, 0.81; 95% CI, 0.75-0.89; P < .001). Regression of ECG LVH was also associated with significantly reduced risks of sudden cardiac death, new-onset atrial fibrillation, hospitalization for heart failure, and new-onset diabetes mellitus.

Conclusions

Regression of ECG LVH by Cornell product and/or Sokolow-Lyon voltage criteria during antihypertensive therapy is associated with lower likelihoods of CV morbidity and mortality, all-cause mortality, and new-onset diabetes, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of ECG LVH may improve prognosis.     

Regression of electrocardiographic left ventricular hypertrophy or strain is associated with lower incidence of cardiovascular morbidity and mortality in hypertensive patients independent of blood pressure reduction – A LIFE review

Cornell product criteria, Sokolow–Lyon voltage criteria and electrocardiographic (ECG) strain (secondary ST-T abnormalities) are markers for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, the relationship of regression of ECG LVH and strain during antihypertensive therapy to cardiovascular (CV) risk was unclear before the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. We reviewed findings on ECG LVH regression and strain over time in 9193 hypertensive patients with ECG LVH at baseline enrolled in the LIFE study.The composite endpoint of CV death, nonfatal MI, or stroke occurred in 1096 patients during 4.8 ± 0.9 years follow-up. In Cox multivariable models adjusting for randomized treatment, known risk factors including in-treatment blood pressure, and for severity ECG LVH by Cornell product and Sokolow–Lyon voltage, baseline ECG strain was associated with a 33% higher risk of the LIFE composite endpoint (HR. 1.33, 95% CI [1.11–1.59]). Development of new ECG strain between baseline and year-1 was associated with a 2-fold increased risk of the composite endpoint (HR. 2.05, 95% CI [1.51–2.78]), whereas the risk associated with regression or persistence of ECG strain was attenuated and no longer statistically significant (both p > 0.05). After controlling for treatment with losartan or atenolol, for baseline Framingham risk score, Cornell product, and Sokolow–Lyon voltage, and for baseline and in-treatment systolic and diastolic blood pressure, 1 standard deviation (SD) lower in-treatment Cornell product was associated with a 14.5% decrease in the composite endpoint (HR. 0.86, 95% CI [0.82–0.90]). In a parallel analysis, 1 SD lower in-treatment Sokolow–Lyon voltage was associated with a 16.6% decrease in the composite endpoint (HR. 0.83, 95% CI [0.78–0.88]).The LIFE study shows that evaluation of both baseline and in-study ECG LVH defined by Cornell product criteria, Sokolow–Lyon voltage criteria or ECG strain improves prediction of CV events and that regression of ECG LVH during antihypertensive treatment is associated with better outcome, independent of blood pressure reduction.     

Associations of Left Ventricular Hypertrophy and Geometry with Adverse Outcomes in Patients with CKD and Hypertension

Background and objectives

Left ventricular hypertrophy (LVH) and abnormal left ventricular (LV) geometry predict adverse outcomes in the general and hypertensive populations, but findings in CKD are still inconclusive.

Design, setting, participants, & measurements

We enrolled 445 patients with hypertension and CKD stages 2–5 in two academic nephrology clinics in 1999–2003 who underwent both echocardiography and ambulatory BP monitoring. LVH (LV mass >100 g/m² [women] and >131 g/m² [men]) and relative wall thickness (RWT) were used to define LV geometry: no LVH and RWT≤0.45 (normal), no LVH and RWT>0.45 (remodeling), LVH and RWT≤0.45 (eccentric), and LVH and RWT>0.45 (concentric). We evaluated the prognostic role of LVH and LV geometry on cardiovascular (CV; composite of fatal and nonfatal events) and renal outcomes (composite of ESRD and all-cause death).

Results

Age was 64.1±13.8 years old; 19% had diabetes, and 22% had CV disease. eGFR was 39.9±20.2 ml/min per 1.73 m². LVH was detected in 249 patients (56.0%); of these, 125 had concentric LVH, and 124 had eccentric pattern, whereas 71 patients had concentric remodeling. Age, women, anemia, and nocturnal hypertension were independently associated with both concentric and eccentric LVH, whereas diabetes and history of CV disease associated with eccentric LVH only, and CKD stages 4 and 5 associated with concentric LVH only. During follow-up (median, 5.9 years; range, 0.04–15.3), 188 renal deaths (112 ESRD) and 103 CV events (61 fatal) occurred. Using multivariable Cox analysis, concentric and eccentric LVH was associated with higher risk of CV outcomes (hazard ratio [HR], 2.59; 95% confidence interval [95% CI], 1.39 to 4.84 and HR, 2.79; 95% CI, 1.47 to 5.26, respectively). Similarly, greater risk of renal end point was detected in concentric (HR, 2.33; 95% CI, 1.44 to 3.80) and eccentric (HR, 2.30; 95% CI, 1.42 to 3.74) LVH. Sensitivity analysis using LVH and RWT separately showed that LVH but not RWT was associated with higher cardiorenal risk.

Conclusions

In patients with CKD, LVH is a strong predictor of the risk of poor CV and renal outcomes independent from LV geometry.     

Relation of baseline plasma phospholipid levels to cardiovascular outcomes at two years in men with acute coronary syndrome referred for coronary angiography

In addition to cholesterol and triglycerides, plasma also contains phospholipids. The choline-containing phospholipids constitute >90% of total plasma phospholipids. To date, no studies have looked specifically at the prognostic significance of total phospholipids in patients with known or suspected coronary artery disease. The present study investigated the long-term prognostic significance of total choline-containing phospholipid levels in a well-characterized cohort of 193 men with acute coronary syndromes who were referred for coronary angiography at a Department of Veterans Affairs Medical Center. All patients were followed prospectively for the development of vascular outcomes. After controlling for a variety of baseline variables (including established biomarkers such high-sensitivity C-reactive protein and fibrinogen), plasma phospholipid values (analyzed as a continuous variable) were a strong and independent predictor of each of the individual end points of all-cause mortality (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41 to 0.90, p = 0.0126), cardiac mortality (HR 0.49, 95% CI 0.29 to 0.81, p = 0.0057), and myocardial infarction (HR 0.71, 95% CI 0.52 to 0.98, p = 0.0342) when using a Cox proportional-hazards model. In addition, baseline phospholipid values were also an independent predictor of the composite outcome of all-cause mortality, fatal or nonfatal myocardial infarction, or stroke (HR 0.66, 95% CI 0.49 to 0.90, p = 0.0075). In conclusion, these data demonstrate that low baseline levels of total choline-containing phospholipid are a strong and independent predictor of cardiovascular outcomes (including mortality) in patients with acute coronary syndromes.     

Long-term outcomes of left bundle branch block in high-risk survivors of acute myocardial infarction: The VALIANT experience

BACKGROUND: In survivors of myocardial infarction (MI), new left bundle branch block (LBBB) is associated with adverse outcomes, but its impact is not well described in post-MI patients with left ventricular (LV) systolic dysfunction and/or heart failure (HF). OBJECTIVES: The aim of this study was to determine if new LBBB is an independent predictor of long-term fatal and nonfatal outcomes in high-risk survivors of MI by reviewing data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. METHODS: In VALIANT, 14,703 patients with LV systolic dysfunction and/or HF were randomized to valsartan, captopril, or both a mean of 5 days after MI. Baseline ECG data were available from 14,259 patients. We assessed the predictive value of new LBBB for death and major cardiovascular outcomes after 3 years, adjusting for multiple baseline covariates including LV ejection fraction. RESULTS: At follow-up, patients with new LBBB (608 [4.2%]) compared with patients without new LBBB had more comorbidities and increased adjusted risk of death (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.2-1.6), cardiovascular death (HR 1.4, 95% CI 1.2-1.7), HF (HR 1.3, 95% CI 1.1-1.6), MI (HR 1.5, 95% CI 1.2-1.9), and the composite of death, HF, or MI (HR 1.4, 95% CI 1.2-1.6). CONCLUSION: In post-MI survivors with LV systolic dysfunction and/or HF, new LBBB was an independent predictor of all major adverse cardiovascular outcomes during long-term follow-up. This readily available ECG marker should be considered a major risk factor for long-term cardiovascular complications in high-risk patients after MI.     

Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation: The Losartan Intervention For End Point Reduction in Hypertension (LIFE) study

OBJECTIVES: We assessed the impact of antihypertensive treatment in hypertensive patients with electrocardiographic (ECG) left ventricular (LV) hypertrophy and a history of atrial fibrillation (AF). BACKGROUND: Optimal treatment of hypertensive patients with AF to reduce the risk of cardiovascular morbidity and mortality remains unclear. METHODS: As part of the Losartan Intervention For End point reduction in hypertension (LIFE) study, 342 hypertensive patients with AF and LV hypertrophy were assigned to losartan- or atenolol-based therapy for 1,471 patient-years of follow-up. RESULTS: The primary composite end point (cardiovascular mortality, stroke, and myocardial infarction) occurred in 36 patients in the losartan group versus 67 in the atenolol group (hazard ratio [HR] = 0.58, 95% confidence interval [CI] 0.39 to 0.88, p = 0.009). Cardiovascular deaths occurred in 20 versus 38 patients in the losartan and atenolol groups, respectively (HR = 0.58, 95% CI 0.33 to 0.99, p = 0.048). Stroke occurred in 18 versus 38 patients (HR = 0.55, 95% CI 0.31 to 0.97, p = 0.039), and myocardial infarction in 11 versus 8 patients (p = NS). Losartan-based treatment led to trends toward lower all-cause mortality (30 vs. 49, HR = 0.67, 95% CI 0.42 to 1.06, p = 0.090) and fewer pacemaker implantations (5 vs. 15, p = 0.065), whereas hospitalization for heart failure took place in 15 versus 26 patients and sudden cardiac death in 9 versus 17, respectively (both p = NS). The benefit of losartan was greater in patients with AF than those with sinus rhythm for the primary composite end point (p = 0.019) and cardiovascular mortality (p = 0.039). CONCLUSIONS: Losartan is more effective than atenolol-based therapy in reducing the risk of the primary composite end point of cardiovascular morbidity and mortality as well as stroke and cardiovascular death in hypertensive patients with ECG LV hypertrophy and AF.     

Heart rate turbulence-based predictors of fatal and nonfatal cardiac arrest (The Autonomic Tone and Reflexes After Myocardial Infarction substudy).

A previous report on heart rate (HR) turbulence showed its value in postinfarction risk stratification. The present study determines the predictive value of HR turbulence in a low-risk population after acute myocardial infarction and provides insight into its pathophysiologic correlates. With use of the database of the The Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) study, data were obtained from 1,212 survivors with a mean duration of follow-up of 20.3 months. The a priori end point was defined as the combination of fatal cardiac arrest and nonfatal cardiac arrest. HR turbulence characterized by turbulence onset (TO) and turbulence slope (TS) was calculated and correlated with baroreflex sensitivity (BRS) and the SD of the normal-to-normal RR intervals (SDNN). A composite index of cardiac autonomic function was assessed by combining HR turbulence (TO and TS), BRS, and SDNN. Both TO and TS correlated moderately but significantly with BRS and SDNN (r = 0.26 to 0.44, p <0.001 for all correlations). On Cox's univariate regression analysis, the RRs for abnormal values of TO, TS, and the combination of abnormal TO and TS were 1.86 (95% confidence interval [CI] 0.96 to 3.61, p = 0.065), 4.08 (95% CI 2.11 to 7.89, p <0.0001), and 6.87 (95% CI 3.06 to 15.45, p <0.0001), respectively. The composite autonomic index (combined TO, TS, BRS, and SDNN) was the strongest risk predictor: for all 4 abnormal factors, RR 16.79 (95% CI 6.01 to 46.89, p <0.0001). On multivariate analysis, abnormal TO and TS, and left ventricular ejection fraction remained as independent predictors: RRs 4.07 (95% CI 1.70 to 9.77, p = 0.0017) and 3.53 (95% CI 1.76 to 7.06, p = 0.0004), respectively. In a separate model, the composite autonomic index was the strongest multivariate risk predictor: RR 8.67 (95% CI 2.72 to 7.65, p = 0.0003) for all abnormal factors, and adjusted for left ventricular ejection fraction. Thus, this study confirms the independent value of HR turbulence in predicting fatal cardiac arrest and nonfatal cardiac arrest in a low-risk post-acute myocardial infarction population. By combining HR turbulence, BRS, and SDNN, a comprehensive assessment of cardiac autonomic reflexes and modulation can be obtained.     

Do Patients with Drug‐Eluting Stent Thrombosis Have a Similar Prognosis to Patients Presenting with ST‐Elevation Myocardial Infarction of de novo Lesions?

Background: Despite significant advances in stent technology and pharmacotherapy, drug‐eluting stent thrombosis (DES‐ST) remains a major complication of percutaneous coronary intervention (PCI) and commonly presents as ST‐elevation myocardial infarction (STEMI). There are currently little data comparing the in‐hospital outcomes of patients presenting with STEMI due to DES‐ST with those due to de novo coronary artery disease (CAD). Methods: Our study comprised 985 consecutive patients who underwent primary PCI for STEMI, 102 of whom were diagnosed as having a definite DES‐ST. The primary end‐point was the in‐hospital composite of death or recurrent myocardial infarction (MI). The secondary end‐point was the in‐hospital maximum rise in creatine kinase (myocardial band [MB] fraction) and troponin I. Results: The DES‐ST group had a higher proportion of patients with diabetes mellitus, hypercholesterolemia, history of ischemic heart disease, coronary revascularization, and chronic renal impairment. The adjusted primary end‐point was higher in the DES‐ST cohort (12.7% vs. 7.4%; P = 0.05). The 2 cohorts did not differ in the secondary end‐point. The independent predictors of the primary end‐point were age (hazard ratio [HR]= 1.04; 95% confidence interval [CI]= 1.01 – 1.06; P = 0.005), cardiogenic shock (HR = 11.5; 95% CI = 6.38 – 20.07, P < 0.001), and lesions involving the left anterior descending coronary artery (HR = 1.8; 95% CI = 1.03 – 3.13, P = 0.04). DES‐ST was not an independent predictor of the primary end‐point (HR = 1.18; 95% CI = 0.53–2.63, P = 0.38). Conclusions: Patients with STEMI secondary to DES‐ST have a poorer in‐hospital outcome than do patients in whom STEMI is due to de novo CAD. This difference may be predominantly driven by differences in the baseline characteristics between these cohorts. (J Interven Cardiol 2011;24:320–325)     

A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study.

BACKGROUND--Although dietary factors are suspected to be important determinants of coronary heart disease (CHD) risk, the direct evidence is relatively sparse. METHODS--The Adventist Health Study is a prospective cohort investigation of 31,208 non-Hispanic white California Seventh-Day Adventists. Extensive dietary information was obtained at baseline, along with the values of traditional coronary risk factors. These were related to risk of definite fatal CHD or definite nonfatal myocardial infarction. RESULTS--Subjects who consumed nuts frequently (more than four times per week) experienced substantially fewer definite fatal CHD events (relative risk, 0.52; 95% confidence interval [CI], 0.36 to 0.76) and definite nonfatal myocardial infarctions (relative risk, 0.49; 95% CI, 0.28 to 0.85), when compared with those who consumed nuts less than once per week. These findings persisted on covariate adjustment and were seen in almost all of 16 different subgroups of the population. Subjects who usually consumed whole wheat bread also experienced lower rates of definite nonfatal myocardial infarction (relative risk, 0.56; 95% CI, 0.35 to 0.89) and definite fatal CHD (relative risk, 0.89; 95% CI, 0.60 to 1.33) when compared with those who usually ate white bread. Men who ate beef at least three times each week had a higher risk of definite fatal CHD (relative risk, 2.31; 95% CI, 1.11 to 4.78), but this effect was not seen in women or for the nonfatal myocardial infarction end point. CONCLUSION--Our data strongly suggest that the frequent consumption of nuts may protect against risk of CHD events. The favorable fatty acid profile of many nuts is one possible explanation for such an effect.     

Prognostic value of serial electrocardiographic voltage and repolarization changes in essential hypertension: the HEART Survey study

BACKGROUND: The interpretation of serial electrocardiographic (ECG) changes in hypertensive subjects is uncertain. We tested the hypothesis that serial changes in repolarization and voltage are independent determinants of outcome. METHODS: The Hypertrophy at ECG And its Regression during Treatment (HEART) Survey was a prospective observational study performed at 61 centers. We studied 711 subjects with hypertension and ECG left-ventricular hypertrophy (LVH) at entry. Tracings from 496 subjects at entry and one or more visits during follow-up were available for central reading. RESULTS: The prevalence of ECG LVH progressively decreased by 49.6% at 3 years. The crude rate of a prespecified primary composite end point of cardiovascular events was 4.17 per 100 subjects per year (95% confidence interval [CI], 3.27 to 5.33). We used Cox regression models of ECG LVH indexes as time-varying covariates at baseline and at follow-up. Time-varying LVH, defined as an absence of ST-T alterations ("strain"), was associated with a lower event rate hazard ratio (HR), 0.47; 95% CI, 0.28 to 0.78; P = .0035), whereas the LVH changes defined in terms of ECG voltages did not achieve significance (HR, 0.91; 95% CI, 0.74 to 1.13; P = .39). The crude event rate in subjects with versus without in-treatment ST-T alterations on the last available ECG before the event or before censoring was 8.38 versus 3.17 per 100 subjects per year (P < .0001). CONCLUSIONS: In this study of subjects with hypertension and ECG LVH at entry, serial changes in repolarization significantly predicted the prognosis, independent of voltage change (which was not significantly predictive in this study). The persistence or new development of ST-T alterations identifies subjects at very high risk of cardiovascular events.     

Usefulness of standard electrocardiographic parameters for predicting cardiac events after acute myocardial infarction during modern treatment era

Comprehensive information about the independent value of different electrocardiographic (ECG) variables in predicting cardiac events after acute myocardial infarction (AMI) in the era of modern therapy is limited. Patients (n = 1,034) underwent standard electrocardiography from 5 to 7 days after an AMI. Several time intervals and PQRST abnormalities were analyzed from the electrocardiogram. During a mean +/- SD follow-up of 752 +/- 301 days on average, 42 patients (4%) experienced cardiac death, and 259 patients (25%) a cardiac death, nonfatal AMI, or unstable angina. Several ECG variables had a significant association with cardiac events in univariate comparisons. After adjustment for all risk variables in the Cox hazards model, lateral ST-segment depression (hazard ratio [HR] 4.76, 95% confidence interval [CI] 2.40 to 9.44, p <0.0001) and atrial abnormality with a terminal deflection of the P wave > or =0.1 mV deep and > or =40 ms in duration in lead V(1) (HR 2.46, 95% CI 1.25 to 4.82, p = 0.009) were the only ECG variables that independently predicted cardiac death. Lateral ST-segment depression also predicted the combined end point of cardiac death/nonfatal AMI/unstable angina in this model (HR 1.49, 95% CI 1.14 to 1.94, p = 0.003). In conclusion, lateral ST depression and atrial abnormality on the electrocardiogram are independent predictors of cardiac death after AMI. Lateral ST depression is also associated with ischemic cardiac events.     

Usefulness of right ventricular fractional area change to predict death, heart failure, and stroke following myocardial infarction (from the VALIANT ECHO Study)

Severe right ventricular dysfunction independent of left ventricular ejection fraction increased the risk of heart failure (HF) and death after myocardial infarction (MI). The association between right ventricular function and other clinical outcomes after MI was less clear. Two-dimensional echocardiograms were obtained in 605 patients with left ventricular dysfunction and/or clinical/radiologic evidence of HF from the VALIANT echocardiographic substudy (mean 5.0 +/- 2.5 days after MI). Clinical outcomes included all-cause mortality, cardiovascular (CV) death, sudden death, HF, and stroke. Baseline right ventricular function was measured in 522 patients using right ventricular fractional area change (RVFAC) and was related to clinical outcomes. Mean RVFAC was 41.9 +/- 4.3% (range 19.2% to 53.1%). The incidence of clinical events increased with decreasing RVFAC. After adjusting for 11 covariates, including age, ejection fraction, and Killip's classification, decreased RVFAC was independently associated with increased risk of all-cause mortality (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.31 to 1.98), CV death (HR 1.62, 95% CI 1.30 to 2.01), sudden death (HR 1.79, 95% CI 1.26 to 2.54), HF (HR 1.48, 95% CI 1.17 to 1.86), and stroke (HR 2.95, 95% CI 1.76 to 4.95), but not recurrent MI. Each 5% decrease in baseline RVFAC was associated with a 1.53 (95% CI 1.24 to 1.88) increased risk of fatal and nonfatal CV outcomes. In conclusion, decreased right ventricular systolic function is a major risk factor for death, sudden death, HF, and stroke after MI.     

EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome

Comprehensive safety evaluation of new drugs for diabetes mellitus is needed in the area of cardiovascular (CV) outcomes, particularly in populations with high CV risk. Alogliptin, a dipeptidyl peptidase 4 inhibitor, is under development for the treatment of type 2 diabetes mellitus alone or in combination with other antidiabetic therapies. Long-term CV safety of alogliptin is being established in a randomized, placebo-controlled clinical study in patients with acute coronary syndrome (ACS) using an analytical approach that has both an interim and final assessment. The primary CV end point for this trial is a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Approximately 5,400 men and women with type 2 diabetes and ACS (acute myocardial infarction or unstable angina) are being recruited and will be followed up for up to 4.5 years postrandomization. The statistical plan for the trial uses a design that evaluates the hazard ratio (HR) of alogliptin to placebo first based on the primary CV composite end point after accrual of 80 to 150 primary CV events and again when there are 550 to 650 primary CV events. In the first series of analyses, the upper bound of a group-sequential 1-sided repeated CI for the HR must be ≤1.8 for registration in the United States. At end of study, the upper bound of a subsequent group-sequential 1-sided repeated CI for the HR must be ≤1.3. For both group sequential analyses, the repeated CIs are calculated to insure simultaneous coverage probabilities of 97.5% for the true HR. Study progress: More than 2,000 ACS patients were randomized as of June 2011. EXAMINE will define the CV safety profile of this dipeptidyl peptidase 4 inhibitor in patients at high risk for CV events.     

Clinical Implications of QRS Duration and QT Peak Prolongation in Patients with Suspected Coronary Disease Referred for Elective Cardiac Catheterization

Background: The electrocardiogram (ECG) remains a simple, universally available, and prognostically powerful investigation in heart failure, and acute coronary syndromes. We sought to assess the prognostic utility of clinical, angiographic, and simple ECG parameters in a large cohort of patients undergoing elective cardiac catheterization (CC) for known or suspected coronary artery disease. Methods: Consecutive consenting patients undergoing CC for coronary disease were enrolled at a single tertiary center. Patient data, drug therapy, catheter reports, and ECG recordings were prospectively recorded in a validated electronic archive. The primary outcome measure was death or nonfatal myocardial infarction (MI) over 1 year or until percutaneous or cardiac surgical intervention. Independent prognostic markers were identified using the Cox proportional hazard model. Results: A total of 682 individuals were recruited of whom 17(2.5%) died or suffered a nonfatal MI in 1 year. In multivariate analysis QRS duration (ms) (HR 1.03 95% CI 1.01–1.05, P = 0.003), extent of coronary disease (HR 2.01 95% CI 1.24–3.58, P = 0.006), and prolonged corrected QT peak interval in lead I (HR 1.02 95% CI 1.00–1.03, P = 0.044) were independently associated with death or nonfatal MI. Receiver‐operator characteristic (ROC) analysis for the multivariate model against the primary end point yielded an area under the curve of 0.759 (95% CI 0.660–0.858), P < 0.001. Conclusions: QRS duration and QT peak are independently associated with increased risk of death or nonfatal MI in stable patients attending for coronary angiography.     

Correction of QRS voltage for body mass index does not improve the prediction of fatal and nonfatal cardiovascular events. The Moli-sani study

Background and aimsThe diagnosis of LVH by ECG may particularly difficult in obese individuals. The aim of this study was to prospectively investigate whether the correction for body mass index (BMI) might improve the prognostic significance for cerebro and cardiovascular events of two electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) in a large cohort of Italian adults.Methods and resultsIn 18,330 adults (54 ± 11 years, 55% women) from the Moli-sani cohort, obesity was defined using the ATPIII criteria. The Sokolow–Lyon (SL) and Cornell Voltage (CV) criteria were used for ECG–LVH. In overweight and obese subjects, as compared with normal weight, the prevalence of ECG–LVH by the SL index was lower. During follow-up (median 4.3 yrs), 503 cerebro and cardiovascular events occurred. One standard deviation (1-SD) increment in uncorrected and in BMI-corrected SL index and CV was associated with an increased risk of events (HR 1.12, 95% CI 1.02–1.22 and HR 1.16, 95% CI 1.06–1.26 and HR 1.12, 95% CI 1.03–1.23 and HR 1.17, 95% CI 1.07–1.27, respectively for SL and CV). In obese subjects, 1-SD increment in uncorrected CV and in BMI-corrected CV was not associated to a significant risk of events (HR 1.05, 95% CI 0.910–1.22 and HR 1.08, 95% CI 0.95–1.23 respectively). Uncorrected SL index showed a significant association with events, which was marginally stronger with BMI-corrected SL voltage (HR 1.18, 95% CI 1.02–1.37 and HR 1.17, 95% CI 1.04–1.33 respectively, Akaike information criterion change from 3220 to 3218).ConclusionsBMI correction of ECG LVH voltage criteria does not significantly improve the prediction of cerebro and cardiovascular events in obese patients in a large cohort at low cardiovascular risk.     

Prognostic Value of a New Electrocardiographic Method for Diagnosis of Left Ventricular Hypertrophy in Essential Hypertension

Objectives. We tested the prognostic value of a new electrocardiographic (ECG) method (Perugia score) for diagnosis of left ventricular hypertrophy (LVH) in essential hypertension and compared it with five standard methods (Cornell voltage, Framingham criterion, Romhilt-Estes point score, left ventricular strain, Sokolow-Lyon voltage).Background. Several standard ECG methods for assessment of LVH are used in the clinical setting, but a comparative prognostic assessment is lacking.Methods. A total of 1,717 white hypertensive subjects (mean age 52 years; 51% men) were prospectively followed up for up to 10 years (mean 3.3).Results. At entry, the prevalence of LVH was 17.8% (Perugia score), 9.1% (Cornell), 3.9% (Framingham), 5.2% (Romhilt-Estes), 6.4% (strain) and 13.1% (Sokolow-Lyon). During follow-up there were 159 major cardiovascular morbid events (33 fatal). The event rate was higher in the subjects with than in those without LVH (all p < 0.001) according to all methods except the Sokolow-Lyon method. By multivariate analysis, an independent association between LVH and cardiovascular disease risk was maintained by the Perugia score (hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.5 to 2.8) and the Framingham (HR 1.91, 95% CI 1.1 to 3.2), Romhilt-Estes (HR 2.63, 95% CI 1.7 to 4.1) and strain methods (HR 2.11, 95% CI 1.4 to 3.2). The Perugia score showed the highest population-attributable risk for cardiovascular events, accounting for 15.6% of all cases, whereas the Framingham, Romhilt-Estes and strain methods accounted for 3.0%, 7.4% and 6.8% of all events, respectively. LVH diagnosed by the Perugia score was also associated with an increased risk of cardiovascular mortality (HR 4.21, 95% CI 2.1 to 8.7), with a population-attributable risk of 37.0%.Conclusions. The Perugia score carried the highest population-attributable risk for cardiovascular morbidity and mortality compared with classic methods for detection of LVH. Traditional interpretation of standard electrocardiography maintains an important role for cardiovascular risk stratification in essential hypertension.     

Estimated glomerular filtration rate, inflammation, and cardiovascular events after an acute coronary syndrome

Both renal dysfunction and elevated levels of high-sensitivity C-reactive protein (CRP) are associated with a higher risk of cardiovascular (CV) outcomes. However, it remains to be established whether the prognostic value of impaired estimated glomerular filtration rate (GFR) remains after accounting for markers of inflammation. METHODS AND RESULTS: Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation in 4178 patients with non-ST or ST-elevation acute coronary syndromes, participating in the A to Z trial. The mean estimated GFR was 68 mL/min, with a median baseline CRP of 20.2 mg/L. Both an estimated GFR <60 mL/min (HR 2.13, 95% CI 1.7-2.6) and a CRP in the fourth quartile (HR 1.7, 95% CI 1.4-2.2) were strong univariate predictors of a CV event (composite of CV death, recurrent myocardial infarction, heart failure, or stroke). After adjusting for baseline CRP, GFR <60 mL/min remained a strong multivariate predictor for CV death (HR 1.82, 95% CI 1.1-2.97). Randomization to high-dose statin therapy was associated with a reduction in the CV composite (adjusted HR 0.69, 95% CI 0.5-0.95) irrespective of baseline renal function. CONCLUSIONS: In a population of patients without overt renal disease, moderate reductions in estimated GFR remain an important prognostic marker. This increased CV hazard associated with an estimated GFR <60 mL/min is independent and additive to markers of inflammation.     

Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians

OBJECTIVES: We sought to prospectively assess whether self-reported periodontal disease is associated with subsequent risk of cardiovascular disease in a large population of male physicians. BACKGROUND: Periodontal disease, the result of a complex interplay of bacterial infection and chronic inflammation, has been suggested to be a predictor of cardiovascular disease. METHODS: Physicians' Health Study I was a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 U.S. male physicians. A total of 22,037 physicians provided self-reports of presence or absence of periodontal disease at study entry and were included in this analysis. RESULTS: A total of 2,653 physicians reported a personal history of periodontal disease at baseline. During an average of 12.3 years of follow-up, there were 797 nonfatal myocardial infarctions, 631 nonfatal strokes and 614 cardiovascular deaths. Thus, for each end point, the study had >90% power to detect a clinically important increased risk of 50%. In Cox proportional hazards regression analysis adjusted for age and treatment assignment, physicians who reported periodontal disease at baseline had slightly elevated, but statistically nonsignificant, relative risks (RR) of nonfatal myocardial infarction, (RR, 1.12; 95% confidence interval [CI], 0.92 to 1.36), nonfatal stroke (RR, 1.10; CI, 0.88 to 1.37) and cardiovascular death (RR, 1.20; CI, 0.97 to 1.49). Relative risk for a combined end point of all important cardiovascular events (first occurrence of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death) was 1.13 (CI, 0.99 to 1.28). After adjustment for other cardiovascular risk factors, RRs were all attenuated and nonsignificant. CONCLUSIONS: These prospective data suggest that self-reported periodontal disease is not an independent predictor of subsequent cardiovascular disease in middle-aged to elderly men.     

Prognostic impact of electrocardiographic left ventricular hypertrophy following transcatheter aortic valve replacement

BackgroundLeft ventricular hypertrophy (LVH) develops with both structural and electrical remodeling in response to elevated afterload due to aortic stenosis (AS). This study evaluated the prognostic value of electrocardiographic LVH (ECG LVH) after transcatheter aortic valve replacement (TAVR).MethodsA retrospective study including 157 consecutive patients who underwent TAVR was conducted. ECG LVH was defined as Sokolow–Lyon voltage (S in V₁ + R in V_5/6) before TAVR was ≥3.5mV. We investigated the association between ECG LVH and the 1-year composite outcome comprising all-cause death and rehospitalization related to heart failure. ECG and echocardiographic measurements at 1, 6, and 12 months after TAVR were assessed.ResultsThe baseline characteristics were comparable between the ECG LVH (n = 74) and non-ECG LVH groups (n = 83). The ECG LVH was associated with a significantly greater reduction of Sokolow–Lyon voltage and LV mass index than the non-ECG LVH after TAVR. The absence of ECG LVH was an independent predictor of the 1-year composite outcome [adjusted hazard ratio (HR), 2.27; 95% confidence interval (CI), 1.01 – 5.60; p = 0.04]. Furthermore, a reduction of Sokolow–Lyon voltage from baseline to 1-month follow-up, but not a reduction of LV mass index, was associated with a lower cumulative composite outcome from 1 month to 1 year (adjusted HR, 0.36; 95% CI, 0.15 – 0.86; p = 0.02).ConclusionsECG LVH was associated with a low incidence of adverse clinical outcomes and greater reverse LV remodeling after TAVR. Preprocedural and serial LVH assessment by ECG might be useful in AS patients undergoing TAVR.     

Chronic Kidney Disease,Basal Insulin Glargine,and Health Outcomes in People with Dysglycemia: The ORIGIN Study

Background

Early stages of chronic kidney disease are associated with an increased cardiovascular risk in patients with established type 2 diabetes and macrovascular disease. The role of early stages of chronic kidney disease on macrovascular outcomes in prediabetes and early type 2 diabetes mellitus is not known. In the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial, the introduction of insulin had no effect on cardiovascular outcomes compared with standard therapy. In this post hoc analysis of ORIGIN, we compared cardiovascular outcomes in subjects without to those with mild (Stages 1-2) or moderate chronic kidney disease (Stage 3).