Four ECG left ventricular hypertrophy criteria and the risk of cardiovascular events and mortality in patients with vascular disease.

OBJECTIVE: The relation between different electrocardiographic left ventricular hypertrophy (ECG-LVH) criteria and cardiovascular risk in patients with clinical manifest arterial disease is unclear. Therefore, we determined the association between four ECG-LVH criteria: Sokolow-Lyon, Cornell product, Cornell/strain index and Framingham criterion; and risk of cardiovascular events and mortality in this population. METHODS: Risk of cardiovascular events was estimated in 6913 adult patients with clinical manifest arterial disease originating from the Secondary Manifestations of ARTerial disease (SMART) cohort. Cox proportional regression analysis was used to estimate the risk of the four ECG-LVH criteria and the primary composite outcome: myocardial infarction (MI), stroke or cardiovascular death; and secondary outcomes: MI, stroke and all-cause mortality; adjusted for confounders. RESULTS: The highest prevalence of ECG-LVH was observed for Cornell product (10%) and Cornell/strain index (9%). All four ECG-LVH criteria were associated with an increased risk of the primary composite endpoint: Sokolow-Lyon (hazard ratio 1.37, 95% CI 1.13-1.66), Cornell product (hazard ratio 1.54, 95% CI 1.30-1.82), Cornell/strain index (hazard ratio 1.70, 95% CI 1.44-2.00) and Framingham criterion (hazard ratio 1.78, 95% CI 1.21-2.62). Cornell product, Cornell/strain index and Framingham criterion ECG-LVH were additionally associated with an elevated risk of secondary outcomes. Cardiovascular risk increased whenever two, or three or more ECG-LVH criteria were present concurrently. CONCLUSION: All four ECG-LVH criteria are associated with an increased risk of cardiovascular events. As Cornell/strain index is both highly prevalent and carries a high cardiovascular risk, this is likely the most relevant ECG-LVH criterion for clinical practice.

Hypertensive target organ damage and the risk for vascular events and all-cause mortality in patients with vascular disease.

OBJECTIVE: Presence of hypertensive target organ damage is related to increased vascular risk and mortality. Whether combined presence of hypertensive target organ damage confers higher vascular risk compared to single presence is unknown. This study evaluates the separate and combined effects of impaired renal function [estimated glomerular filtration rate (eGFR) ≤60 ml/min per 1.73 m], albuminuria (albumin/creatinine-ratio men ≥2.5 mg/mmol, women ≥3.5 mg/mmol) and left-ventricular hypertrophy (LVH) (Sokolow-Lyon and/or Cornell-voltage criterion) on the occurrence of vascular events and mortality in patients with vascular disease (coronary artery disease, cerebrovascular disease, and peripheral arterial disease). METHODS AND RESULTS: A cohort of patients with vascular diseases (n = 4319) was followed (median 4.4 years) for the occurrence of vascular events (stroke, myocardial infarction, vascular death) and mortality. LVH was present in 11%, impaired renal function in 15%, and albuminuria in 18%. Presence of at least two hypertensive target organ damage was prevalent in 8%. The risk for vascular events was hazard ratio 1.5 [95% confidence interval (CI) 1.2-1.9] for presence of one hypertensive target organ damage and hazard ratio 3.8 (95% CI 2.3-6.3) for three manifestations of hypertensive target organ damage (adjusted for age, sex). For mortality this was hazard ratio 1.4 (95% CI 1.1-1.7) and hazard ratio 3.2 (95% CI 1.9-5.2). Hazard ratios for single presence of different types of organ damage were comparable and independent of the presence of hypertension. CONCLUSIONS: Impaired renal function, albuminuria, and LVH are prevalent in patients with vascular disease and confer independent and additive risk for vascular events and mortality. Measurement of hypertensive target organ damage in patients with vascular disease identifies patients at very high risk and may have treatment implications.

The risk of resting heart rate on vascular events and mortality in vascular patients.

BACKGROUND: Resting heart rate (RHR) reflects sympathetic nerve activity and is independently related to the occurrence of cardiovascular events and death in healthy subjects, patients with coronary artery disease (CAD) and patients with cardiovascular risk factors. We investigated and compared the risk of RHR on the occurrence of cardiovascular events and death in patients with CAD, cerebrovascular disease (CVD), peripheral arterial disease (PAD) or abdominal aortic aneurysm (AAA). METHODS: Data were used from a prospective cohort study of 4272 patients with manifest vascular disease: CAD (n=2244), CVD (n=930), PAD (n=823) or AAA (n=275). RHR was obtained at baseline from an electrocardiogram. The median follow-up time was 4.4 (interquartile range 2.1-7.4) years. The relation between RHR and the occurrence of cardiovascular events and death was estimated by Cox proportional hazard analyses. RESULTS: Each increase in RHR of 10 beats/min was related to an increased risk for all-cause mortality (hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.07-1.21) and vascular mortality (HR 1.15; 95% CI 1.06-1.25), but not for myocardial infarction (HR 1.03; 95% CI 0.94-1.14) or ischemic stroke (HR 1.05; 95% CI 0.92-1.20). The relation between an increased RHR and increased risk for all-cause mortality was present irrespective of beta-blocker use and irrespective of the location of vascular disease: CAD (HR 1.23; 95% CI 1.05-1.44), CVD (HR 1.18; 95% CI 1.05-1.33) and PAD/AAA (HR 1.10; 95% CI 1.01-1.20). CONCLUSIONS: Elevated RHR is associated with increased risk for mortality but not for myocardial infarction or stroke in patients with manifest vascular diseases irrespective of location of vascular disease.

Relation between abdominal obesity, insulin resistance and left ventricular hypertrophy diagnosed by electrocardiogram and magnetic resonance imaging in hypertensive patients.

Obesity is related to left ventricular hypertrophy (LVH). Whether LVH on electrocardiography (ECG-LVH) is a result of increased cardiac electrical activity or due to increased left ventricular mass (LVM) remains to be determined. The aims of the present study were to investigate the relation between obesity and ECG-LVH and LVM by magnetic resonance imaging (MRI-LVM) in patients with hypertension and to investigate the relation of insulin resistance (IR) and LVH. Patients with hypertension (n = 421) were evaluated using Sokolow-Lyon voltage, Cornell voltage, and cardiac magnetic resonance imaging. Waist circumference was used as a measure of abdominal obesity. Linear regression analysis revealed an inverse relation (adjusted ß = -0.02, 95% confidence interval -0.02 to -0.01) between waist circumference and Sokolow-Lyon voltage, indicating a decrease of 0.02 mV per 1-cm increase in waist circumference. There was a positive relation between waist circumference and MRI-LVM (ß = 0.49, 95% confidence interval 0.32 to 0.67). Patients in the highest quartile of LVM had a worse metabolic profile than patients with the Sokolow-Lyon voltage criterion. The relations of IR with ECG-LVH and MRI-LVM were similar to those of waist circumference in relation to ECG-LVH and MRI-LVM. In conclusion, there is an inverse relation between waist circumference and ECG-LVH and a positive relation between waist circumference and MRI-LVM. This study indicates that obesity has a different relation to voltage criteria for LVH compared to anatomic criteria for LVH, supporting the hypothesis that IR decreases electrocardiographic voltages, despite an increase in MRI-LVM. The clinical implication is that especially in patients with IR, Sokolow-Lyon voltage is low in contrast to high MRI-LVM.

The prevalence of obesity-related hypertension and risk for new vascular events in patients with vascular diseases.

Higher body weight is associated with an increased prevalence of vascular risk factors. Obesity leads to hypertension by various mechanisms, often referred to as obesity-related hypertension. Aim of the present study was to evaluate the prevalence and the vascular risk of the combination of obesity and hypertension in patients with vascular diseases. A cohort of patients with various clinical manifest vascular diseases (n = 4,868) was screened for vascular risk factors and followed (median follow-up 4.2 years) for the occurrence of vascular events (stroke, myocardial infarction, and vascular death). The prevalence of obesity was 18% (95% confidence interval (CI) 17-19%) and the prevalence of hypertension was 83% (95% CI 82-84%). The prevalence of the combination of obesity and hypertension was 16% (95% CI 15-17%). Patients with high blood pressure (BP) combined with a high weight (highest tertile systolic BP (SBP) in the highest tertile BMI) were not at higher risk for new vascular events (hazard ratios (HR) 1.29; 95% CI 0.89-1.88) or mortality (HR 1.18; 95% CI 0.81-1.73) compared to patients without high BP and high weight (patients in the lowest tertile of SBP in the lowest tertile of BMI). Patients with only high weight did not have an elevated risk either for vascular events (HR 1.34; 95% CI 0.91-1.98) or mortality (HR 1.22; 95% CI 0.81-1.83) compared to patients without high BP and high weight. The prevalence of the combination of hypertension and obesity is low in patients with vascular diseases and does not confer a higher risk for recurrent vascular diseases and mortality than each risk factor alone.

Risk of elevated resting heart rate on the development of type 2 diabetes in patients with clinically manifest vascular diseases.

OBJECTIVE: Sympathetic nerve activation is causally related to insulin resistance as both a cause and a consequence. Resting heart rate (RHR) reflects sympathetic nerve activity. We investigated the effect of RHR on the incidence of type 2 diabetes mellitus (T2DM) in patients with clinically manifest vascular diseases. DESIGN: Data were used from the second manifestations of arterial disease (SMART) study: a prospective cohort study of patients with clinically manifest vascular diseases (n=3646). METHODS: RHR was obtained using an electrocardiogram. Patients were followed up for incident type 2 diabetes (n=289) during a median period of 5.5 (interquartile range 3.2-8.4) years. The relation between RHR and incident T2DM was estimated by Cox proportional hazard analysis. As age was an effect modifier (P=0.048), analyses were stratified for age. RESULTS: Patients in quartile 4 (Q4) of RHR had a 65% increased risk of T2DM compared with those in Q1 (reference; hazard ratios (HR), 1.65; 95% confidence interval (95% CI), 1.15-2.36) adjusted for age, gender, smoking, estimated glomerular filtration rate, systolic blood pressure, location of vascular disease, and antihypertensive medication. Every 10 beats per minute (bpm) increase in RHR increased the risk for T2DM with 10% (HR, 1.10; 95% CI, 1.00-1.21) in the total population. This risk was particularly high in subjects aged 55-63 years (per 10 bpm: HR, 1.22; 95% CI, 1.04-1.43) and was independent of the location of vascular disease and beta-blocker use. CONCLUSIONS: Increased RHR, an indicator of sympathetic nerve activity, is associated with an increased risk for T2DM in patients with manifest vascular diseases, particularly in middle-aged patients.

Increased visceral adipose tissue is associated with increased resting heart rate in patients with manifest vascular disease.

Abdominal obesity is characterized by sympathetic nerve activation (SNA), probably mediated by elevated insulin and leptin levels. Resting heart rate (RHR) is a marker of sympathetic tone, and independently associated with cardiovascular events and death in various populations. We investigated and quantified the relation between visceral adipose tissue (VAT) and RHR in patients with vascular disease. In 3,723 patients with manifest vascular disease, visceral and subcutaneous fat tissue was measured with ultrasonography. RHR was obtained from an electrocardiogram (ECG). The association between quartiles of VAT and RHR was quantified using linear regression analysis with adjustments for potential confounding factors. Separate analyses were performed for men and women and for location of vascular disease. Visceral fat was categorized into sex-pooled quartiles (Q) ranging from 2.7-8.0 cm in Q1 (reference) to 9.4-20.6 cm in Q4. High visceral fat thickness was associated with increased RHR, in men (Q4 vs. Q1, ß = 4.36; 95% confidence interval (CI) = 3.11-5.61) and women (ß = 1.48; 95% CI = -0.70 to 3.66), after full adjustment. Waist circumference and BMI had a significant relation with RHR in men (ß = 3.51; 95% CI = 2.21-4.81 and ß = 2.80; 95% CI = 1.51-4.08, respectively) but these relations were smaller and not significant in women (ß = 0.71; 95% CI = -1.44 to 2.85 and ß = 0.24; 95% CI = -1.90 to 2.37, respectively). There was no relation between subcutaneous fat and RHR in men and women. The relation between visceral fat and RHR was similar in patients with different locations of vascular diseases. Increased visceral fat is associated with increased RHR in male and female patients with vascular disease, independent of the location.