Risk Factor For Left Ventricular Hypertrophy Research Articles

Association between transforming growth factor β1 polymorphisms and left ventricle hypertrophy in essential hypertensive subjects

Left ventricular hypertrophy (LVH) increases the risk of cardiovascular morbid events in hypertension. TGF-beta1 is involved in pathologic states such as cardiac hypertrophy and cardiac fibrosis; we thus postulate that the TGF-beta1 polymorphism is related to LVH in hypertensives. Six hundred and eighty essential hypertensive patients were recruited. Biochemical variables and clinical data were obtained and the determination of LVH was performed by echocardiography. According to the presence of LVH, all subjects were divided into the LVH+ and LVH- group. DNA was obtained, and two coding region polymorphisms of the TGF-beta1 gene (+869 Leu-->Proat codon 10 and +915 ARG-->Pro at codon 25) were analyzed by the polymerase chain reaction. The product was cleaved with the restriction endonucleases. For the polymorphisms of the +869 Leu-->Pro at codon 10, there was no marked difference in the distributions of genotypes and the allele frequencies between the LVH+ and LVH- subjects. For +915 Arg-->Pro at codon 25, a significant difference in the distributions of genotypes of TGF-beta1 was observed. The left ventricular mass index (LVMI) in Arg-Pro genotype carriers was significantly higher than those in the Arg-Arg and Pro-Pro carriers. Multivariate analysis showed that the Arg-Pro genotype was an independent risk factor for LVH (OR 3.23, 95% CI [1.48-5.63, P = 0.002]). The codon 10 genotypes did not show a significant association to LVH. Our data revealed a genetic association of TGF-beta1+915 Arg-->Pro at codon 25 polymorphism with LVH in a Chinese hypertensive population.

Sex Difference in the Prevalence of Left Ventricular Hypertrophy in Dialysis Patients

Background: Left ventricular hypertrophy (LVH) is an important, independent negative predictor of cardiovascular morbidity and mortality in the general population and in dialysis patients. Previous studies suggest a sex dimorphism in the prevalence of LVH; however, this issue has never been approached in dialysis patients. Methods: This study enrolled 237 prevalent dialysis patients: 49 on hemodialysis (HD) and 188 on peritoneal dialysis (PD) from a single center. LVH was defined by echocardiography measurements, which were normalized to body surface area (BSA) and height^2.7, respectively. Results: The mean ages in HD and PD patients were 60 ± 14 and 60 ± 13 years, with a median dialysis vintage of 43 and 20 months, respectively. Although there was no significant difference in age, diabetes, proportion of uncontrolled hypertension, antihypertensive medication and blood pressure between male and female patients within each dialysis modality, the prevalence of LVH (whether indexed to BSA or height^2.7) was consistently higher in females than in males. When these patients were divided into LVH or non-LVH groups, a significant difference in sex distribution was observed between the two groups (62.0% vs. 41.0% when the BSA-indexed standard was used, p < 0.01; 62.8% vs. 37.1% when the height^2.7-indexed standard was used, p < 0.001). In logistic regression analysis, female sex was identified as a risk factor of LVH (odds ratio, OR = 2.48, 95% confidence interval, CI = 1.33–4.59; when BSA-indexed LVH was treated as dependent variable, and OR = 4.05, 95% CI = 1.96–8.38, when height^2.7-indexed LVH was treated as dependent variable) even after adjustment for age, diabetes, blood pressure and antihypertensive medication. Conclusion: This study showed that the prevalence of LVH determined by echocardiography was significantly higher in female dialysis patients than in male dialysis patients. Compared with males, female patients had a 2.5- to 4-fold higher risk to develop LVH even after adjustment for other potential confounding factors, which may indicate that elderly females in the uremic scenario are more prone to develop LVH than elderly males.

Abstract 5160: Obesity is Related to Concentric Left Ventricular Hypertrophy: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)

Obesity is a risk factor for cardiovascular disease but its association with left ventricular (LV) morphologic adaptations is debated because of obesity-associated co-morbidities. We evaluated the relationship of obesity to ventricular size and remodeling independent of other risk factors for LV hypertrophy. 5004 participants (age 45– 84 years; 52% female) of the MESA study free of clinical cardiovascular disease underwent cardiac MRI to assess LV size and function. The association of LV indices with measures of obesity, including fat mass (FM), body mass index (BMI) and waist circumference (WC), was determined using generalized additive models adjusted for established risk factors for LV hypertrophy and fat-free mass (FFM). FFM of participants was estimated based on height-weight models derived from bioelectrical impedance studies and FM was obtained by subtracting FFM from weight. LV mass and end diastolic volume were positively associated with FM, BMI and WC after adjustment for risk factors and FFM. For a given FFM, LV mass/volume ratio increased with FM up to approximately 50 kg FM (Figure ). Cardiac output and stroke volume were also positively associated with FM (slopes: CO 0.02 L/min per kg FM, SV 0.16 ml per kg FM, p&lt;0.001 for each). Ejection fraction showed no significant association with FM. The associations of fat mass to increased LV mass and LV mass/volume were similar in patients with and without obesity associated co-morbidities. Obesity is associated with concentric LV hypertrophy, marked by increased LV mass/volume ratio, increased cardiac output and preserved ejection fraction.

Disproportionately High Risk of Left Ventricular Hypertrophy in Indo‐Asian Women: A Call for More Studies

Indo-Asians have one of the highest rates of cardiovascular disease worldwide. Estimates and determinants of left ventricular hypertrophy (LVH) in this population are not known. We sought to determine the prevalence of and risk factors for LVH in Karachi, Pakistan. We conducted a population-based cross-sectional study on 320 randomly selected adults from the general population aged 40 years or above. LVH was defined as increased left ventricular mass index (LVMI) on echocardiogram (>115 g/m(2) in men and >95 g/m(2) in women) employing the adjusted Devereux equation. Multivariable models were built and logistic regression analysis was done for the primary outcome of LVH. Mean age of subjects was 52.7 (10.4) years, 50% were women. Mean LVMI (SD) was 72.0 (19.2) [median 71.1] g/m(2) in men and 75.7 (25.9) [median 72.9] g/m(2) in women. The overall prevalence of LVH was 21.9% in women and 2.5% in men (P < 0.001). The factors (odds ratio, 95% CI) independently associated with LVH were women versus men (11.35, 3.79-34.02), systolic blood pressure > versus <or= 140 mmHg (2.70, 1.23-5.93), waist circumference (1.05, 1.02-1.08 for each cm increase) and illiteracy (2.43, 1.07-5.52). Urban Pakistani women appear to have a disproportionately high risk of LVH compared to men using standard echocardiographic criteria. Further research is needed to verify these results by establishing population-specific reference values for LVH and correlating cut-points for increased LVMI with prognosis. Concerted efforts are needed to reduce the high burden of risk factors in Indo-Asian women.

Development and Validation of a Clinical Score to Identify Echocardiographic Left Ventricular Hypertrophy in Patients With Cardiovascular Disease

Echocardiographic (echo) left ventricular hypertrophy (LVH) is an independent predictor of mortality. Despite this, screening for LVH in patients with overt cardiovascular diseases is not universally done. To help target echo screening for LVH in patient population, we developed and validated a simple clinical score to help identify those likely to have echo LVH. We performed two studies. The development cohort consisted of 267 patients with angina. The validation cohort consisted of 227 patients with peripheral arterial disease. The prevalence of echo LVH in both patient cohorts was 50%. Six independent predictors of LVH were identified in the development cohort: age >65 years (1 point), body mass index >30 kg/m2 (1 point), history of hypertension (1 point), previous myocardial infarction (1 point), clinic blood pressure >130/80 mm Hg (1 point) and bundle branch block (BBB) on electrocardiogram (4 points). Our clinical score was strongly associated with the presence of LVH in the validation cohort. It also showed a significant continuous positive relationship (P trend <0.001 in males and P trend = 0.006 in females) with increasing quartiles of LV mass in both cohorts. In those without BBB, a modified clinical score performed equally well. We have developed a simple clinical score which quantifies the chance that any patient with manifest cardiovascular disease has the added risk factor of LVH. This will help target precious echo resources toward individuals who are most likely to have this condition. This could potentially lead to better risk stratification in this patient population.

Renal Function Dependent Association of AGTR1 Polymorphism (A1166C) and Electrocardiographic Left-Ventricular Hypertrophy

The association of renin-angiotensin system (RAS) polymorphisms and left-ventricular hypertrophy (LVH) may depend on the presence of risk factors for LVH, such as renal dysfunction. We studied whether renal function modulates the association between RAS polymorphisms and LVH in a cross-sectional study of 8592 inhabitants of Groningen. Left-ventricular hypertrophy was determined with electrocardiograms, using the Cornell voltage-duration product. The following RAS polymorphisms were determined: angiotensin II type-1 receptor (AGTR1 A1166C), angiotensin-converting enzyme (ACE) insertion/deletion (I/D), and angiotensinogen (AGT G-6A). The AGTR1 A1166C and ACE I/D polymorphisms were in Hardy-Weinberg equilibrium. Electrocardiographic LVH was present in 417 (5.0%) subjects. Subjects with LVH were older (53 v 49 years) and overall had more cardiovascular risk factors. Using logistic regression, creatinine clearance interacted with the relationship between the AGTR1 A1166C polymorphism and LVH (beta, -0.19; P = .033). In subjects with the CC genotype, in contrast to carriers of an A allele, the prevalence of LVH increased with more pronounced renal dysfunction. Creatinine clearance also interacted with the relationship between the ACE I/D polymorphism and LVH (beta, 0.12; P = .037), although less strongly, and the other way around. Creatinine clearance did not influence the association between the AGT G-6A polymorphism and LVH (beta, -0.006; P = .491). In this population-based study, the AGTR1 A1166C polymorphism was associated with LVH, dependent on concomitant renal dysfunction. A weaker renal function dependent association between the ACE I/D polymorphism and LVH was also observed. Renal function should be taken into account as a relevant environmental factor for the pathogenetic effects of RAS polymorphisms.

High-Density Lipoprotein Cholesterol and Insulin Resistance Are Independent and Additive Markers of Left Ventricular Hypertrophy in Essential Hypertension

We examined whether plasma high-density lipoprotein-cholesterol (HDL-C) levels and glucose metabolism parameters are independent or additive predictors of left ventricular hypertrophy (LVH) in patients with untreated essential hypertension. The study group consisted of 41 Japanese patients with untreated essential hypertension and LVH (left ventricular mass index [LVMI] >125 g/m2; age 58+/-6 years, mean+/-SD), and the control group consisted of 39 age-matched patients with untreated essential hypertension without LVH (LVMI <or=125 g/m2; age 58+/-7 years). The following metabolic parameters were higher in the group with LVH: fasting plasma glucose (FPG) (p<0.01), fasting insulin concentration (F-IRI) (p<0.0001), and homeostasis model assessment (HOMA)-index (p<0.0001). Among the laboratory parameters investigated, plasma HDL-C levels were lower (p<0.0001), and triglyceride and uric acid levels were higher in the group with LVH (p<0.05 for both). The nighttime systolic and diastolic ambulatory blood pressure (ABP) (p<0.0001, p<0.01, respectively) and nighttime heart rate (p<0.01) were higher in patients with LVH. Multivariate logistic analysis identified HDL-C (odds ratio [OR]=0.92, 95% confidence interval [CI]=0.87-0.98, p<0.05), HOMA-index (OR=3.83, 95% CI=1.28-11.5, p<0.05) and nighttime systolic ambulatory blood pressure (ABP) (OR=1.06, 95% CI=1.00-1.13, p<0.05) as independent significant risk factors for LVH. Our findings suggest that HDL-C, HOMA-index and nighttime systolic ABP are independent predictors for the presence of LVH in Japanese patients with essential hypertension.

Reverse white-coat effect as an independent risk for left ventricular concentric hypertrophy in patients with treated essential hypertension

Recent studies have shown that the converse phenomenon of white-coat hypertension called 'reverse white-coat hypertension' or 'masked hypertension' is associated with poor cardiovascular prognosis. We assessed the hypothesis that this phenomenon may specifically influence left ventricular (LV) structure in treated hypertensive patients. A total of 272 outpatients (mean age, 65 years) with chronically treated essential hypertension and without remarkable white-coat effect were enrolled. Patients were classified into two groups according to office and daytime ambulatory systolic blood pressure (SBP); that is subjects without (Group 1: office SBP > or =daytime SBP, n=149) and with reverse white-coat effect (Group 2: office SBP<daytime SBP, n=123). LV mass index and relative wall thickness were echocardiographically determined. In all subjects, LV mass index and relative wall thickness were positively correlated with daytime and 24-h SBP, but not with office SBP. In addition, these two indices were inversely correlated with office--daytime SBP difference. LV mass index (136+/-31 and 115+/-28 g/m(2), mean+/-s.d.) and relative wall thickness (0.49+/-0.09 and 0.46+/-0.07) were significantly greater in Group 2 than in Group 1. As for LV geometric patterns, Group 2 had a significantly higher rate of concentric hypertrophy compared with Group 1 (48 and 28%). Multivariate analyses revealed that the presence of reverse white-coat effect was a predictor for LV concentric hypertrophy, independent of age, sex, hypertension duration, antihypertensive treatment and ambulatory blood pressure levels. Our findings demonstrate that reverse white-coat effect is an independent risk factor for LV hypertrophy, especially concentric hypertrophy, in treated hypertensive patients.

Regression of left ventricular hypertrophy after bilateral nephrectomy

Left ventricular hypertrophy (LVH) is common inhypertensive patients and predicts heart failure,arrhythmia, cerebrovascular complications and death.LVH is endemic in end-stage renal disease (ESRD).Risk factors for LVH in ESRD patients includehypertension, anaemia, secondary hyperparathyroid-ism and arteriovenous fistulae. LVH is a powerfulpredictor of cardiac morbidity and mortality in theESRD population [1,2]. Regression of LVH has beenreported in ESRD patients after blood pressure (BP)reduction with angiotensin converting enzyme inhibi-tors (ACE-Is), or angiotensin receptor antagonists(ARB) [3,4], and after erythropoietin therapy foranaemia.We report a case in which dramatic regression inLVH was documented on magnetic resonance images(MRIs) of the heart performed before and afterbilateral nephrectomy.Cardiologists use measurements of left ventricular(LV) mass, relative wall thickness and mass–volumeratio to diagnose LVH. Data about LV mass andgeometry in dialysis patients are based on echocardio-graphy which is highly dependent upon operatorskill, individual patient anatomy and mathematicalassumptions. Changes in extracellular volume duringand between dialysis treatments can also cause sub-stantial variations in echocardiographic measurements.Cardiac MRI measures the heart independent ofoperator skill or patient habitus. MRI assessments ofLVmass,relativewallthicknessandmass–volumeratiorely on direct measurements rather than geometricalassumptions which have never been proven to apply tothe ESRD ventricle [5].

Pressure Overload and Cardiac Remodelling-A Smoking Gun Points to Uncoupled Nitric Oxide Synthase: Oxidant Stress from Nitric Oxide Synthase-3 Uncoupling Stimulates Cardiac Pathologic Remodeling from Chronic Pressure Load. J Clin Invest 115: 1221-1231, 2005.

Pressure Overload and Cardiac Remodelling-A Smoking Gun Points to Uncoupled Nitric Oxide Synthase: Oxidant Stress from Nitric Oxide Synthase-3 Uncoupling Stimulates Cardiac Pathologic Remodeling from Chronic Pressure Load. J Clin Invest 115: 1221-1231, 2005.

Pre-Clinical and Clinical Experience of Telmisartan in Cardiac Remodelling

Epidemiological studies have established that left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular and cerebrovascular morbidity and mortality. In turn, hypertension is a well-established risk factor for LVH. Ambulatory blood pressure monitoring has shown that 24-h mean ambulatory blood pressure is a particularly powerful predictor of LVH, being superior to casual clinic blood pressure measurements. The magnitude of the rise in blood pressure in the early morning correlates with the extent of LVH. Prospective studies have shown the advantageous effects of antihypertensive therapy on LVH in terms of regression of left ventricular mass (LVM) and subsequent reduction in overt cardiovascular disease. Meta-analysis has identified differences in the ability of different classes of anti-hypertensive agents to bring about regression of LVH, with agents that target the renin angiotensin system (RAS) appearing superior to other agents, such as beta-blockers and diuretics. The distinct pharmacological features of telmisartan suggest that it may be a suitable agent for managing hypertensive patients because it provides sustained control of blood pressure and appears to be very effective in reversing cardiac remodelling. Pre-clinical evaluation has demonstrated that telmisartan suppresses angiotensin II-induced collagen production and secretion by cultured fibroblasts, and reduces left ventricular weight in different animal models. Several clinical studies have demonstrated that, as well as reducing blood pressure (including 24-h mean ambulatory values), telmisartan brings about LVM regression in patients with hypertension, and improves left ventricular and left atrial function. Comparative studies have shown telmisartan's superiority compared with both hydrochlorothiazide and carvedilol in regressing LVM, the additional activity probably being explained by the sustained blood pressure control and the non-haemodynamic effects of targeting the RAS. The ultimate proof of the clinical value of telmisartan will be provided by the outcome trials ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) currently being conducted in high-risk patients.

An Association Between Inflammatory State and Left Ventricular Hypertrophy in Hemodialysis Patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1β, IL-6, TNF-α, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r = 0.556, p = 0.001), diastolic BP (r = 0.474, p = 0.004), and serum levels of TNF-α (r = 0.446, p = 0.009).Multiple regression analysis showed that systolic BP and TNF-α levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 ± 8.7 vs. 7.3 ± 0.7 pg/mL, p = 0.001). Predialysis serum levels of TNF-α in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 ± 3 vs. 7 ± 1.45 pg/mL, respectively, p > 0.05). However, serum levels of IL-6 and TNF-α significantly elevated after HD, when compared to predialysis levels (from 15.7 ± 8.7 to 17.8 ± 9.5 pg/mL, p = 0.001 and from 8.3 ± 3.0 to 9.9 ± 3.5 pg/mL p = 0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-α in particular, seem to be associated with LVH in ESRD patients.

The Association of Thyroid Function with Cardiac Mass and Left Ventricular Hypertrophy

Decreased serum TSH levels predict cardiovascular mortality, which could be explained by left ventricular hypertrophy (LVH). The aim of this analysis was to investigate the association between thyroid function and LVH. The population-based Study of Health in Pomerania was conducted in a previously iodine-deficient area. Data of 1510 individuals at least 45 yr of age with echocardiography and without thyroid disorders were analyzed. LVH was defined as a left ventricular mass index (LVMI) exceeding 150 g/m(2) (men) or 120 g/m(2) (women). Overt hyperthyroidism was associated with LVMI (P < 0.01), whereas euthyroid subjects and those with elevated TSH levels did not significantly differ with regard to LVMI. LVH was observed in three (15.0%) subjects with elevated serum TSH levels, in 127 (10.5%) euthyroid persons, in 24 (12.5%) individuals with decreased serum TSH levels, and in four (57.1%) subjects with hyperthyroidism (P < 0.01). Logistic regression analysis identified overt hyperthyroidism as an independent risk factor for LVH (odds ratio, 13.65; 95% confidence interval, 2.83-65.75; P < 0.01). There is an association between thyroid function status, cardiac mass, and LVH. Hyperthyroidism is an independent risk factor for LVH.

Echocardiographic changes and risk factors for left ventricular hypertrophy in children and adolescents after renal transplantation.

Long-term consequences of cardiac alteration in children with chronic renal failure and after renal transplantation are largely unknown. In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular hypertrophy (LVH) or left ventricular dilatation. The correction of uremic state by renal transplantation leads to normalization of left ventricular contractility, regression of LVH and improvement of cavity volume and so dialysis patients with uremic cardiomyopathy would benefit from renal transplantation. We studied 73 patients, aged 17 yr or less, who underwent renal transplantation in our center. This cross-sectional study was performed 4.6 yr (median) after transplantation. Of the total, 48 were males and 25 were females. Transthoracic echocardiographic examination was performed for all cases. The effects of clinical, demographic, biochemical and therapeutic data on echocardiographic parameters were assessed. Multivariate analysis was used to assess the relation between the risk factors and the left ventricular muscle mass index. The most common echocardiographic abnormalities were the LVH (47.9%), left atrial enlargement (31.5%) and left ventricular dilatation and systolic dysfunction (13.7% for each). The pretransplant dialysis, arteriovenous fistula, acute rejection, cumulative steroid dose per square meter surface area, post-transplant hypertension, anemia and graft dysfunction were significant risk factors for LVH by univariate analysis. The significant factors by multivariate analysis were pretransplant dialysis, post-transplant hypertension and anemia. From this study we may conclude that LVH is a common problem among renal transplant children and adolescents. Early transplantation, control of hypertension and correction of anemia may be beneficial regarding left ventricular function and structure.

Association of kidney function and hemoglobin with left ventricular morphology among African Americans: The Atherosclerosis Risk in Communities (ARIC) study

Background: Left ventricular (LV) hypertrophy (LVH) is present in more than 70% of patients with kidney failure. Hypertension and anemia, 2 strong risk factors for LVH, are common in patients with moderate kidney dysfunction. It is unknown whether kidney function and lower hemoglobin levels are associated with LV morphological characteristics among African Americans with moderate kidney dysfunction, independent of blood pressure. Methods: As part of the Atherosclerosis Risk in Communities Study, 1,968 African Americans aged 50 to 75 years underwent an echocardiogram after 6 to 9 years of follow-up. LV mass was indexed (LVMI) to body surface area. Glomerular filtration rate (GFR) was estimated from calibrated serum creatinine levels measured at baseline and after 3 years (<30 mL/min/1.73 m2 excluded). Hemoglobin was measured at baseline and after 3 years. Blood pressure was measured every 3 years. Results: A mean GFR of 30 to 59 mL/min/1.73 m2 was associated with a 15.3 g/m2 greater LVMI, 0.9 mm greater posterior wall thickness, and 1.0 mm greater interventricular septal thickness compared with a GFR of 90 mL/min/1.73 m2 or greater. These associations remained after adjustment for age, sex, hemoglobin level, blood pressure, and other covariates. Wall thickness and LVMI increased with lower GFR less than 75 mL/min/1.73 m2 (5.5 g/m2 greater LVMI [95% confidence interval (CI), 0.9 to 10.1] per 10 mL/min/1.73 m2 lower GFR). A lower hemoglobin level was associated with greater LV diameter (0.5 mm [95% CI, 0.2 to 0.7] per 1 g/dL [10 g/L]), but not wall thickness, after adjustment. Conclusion: These results in a general population sample of middle-aged African Americans suggest that moderately decreased kidney function independently predicts greater LV wall thickness, and lower hemoglobin level independently predicts greater LV diameter. These findings may explain, in part, the high risk for cardiovascular disease observed among individuals with kidney disease.

Prospective trials on anemia of chronic disease: The Trial to Reduce Cardiovascular Events with Aranesp® Therapy (TREAT): Management of comorbidities in kidney disease in the 21st century: Anemia and bone disease

Chronic kidney disease (CKD) is emerging as a major public health problem in the United States. Between 1973 and 1999 there was a more than 30-fold increase in the number of patients enrolled in the Medicare funded end-stage renal disease (ESRD) program, from approximately 10,000 to 340,000 [1]. The annual incidence of ESRD has nearly doubled from 48,350 patients (190 per million) in 1991 to 89,252 (317 per million) in 1999. Estimates from the Third National Health and Nutrition Examination Survey (NHANES III), using the glomerular filtration rate (GFR) equation from the Modification of Diet in Renal Disease (MDRD) study [2, 3], showed that the prevalence of CKD, defined as a GFR 60 mL/min /1.73 m2, was approximately 8.3 million individuals, or 4.7% [4]. The MDRD Study indicated that 85% of patients with impaired kidney function (GFR 55 mL/min/1.73m2) have progressive losses of kidney function at a rate of 4 mL/min per year [5]. The progressive nature of CKD, and epidemiologic factors that include population aging, increasing prevalence of type II diabetes and hypertension, improved survival of patients on dialysis, and the acceptance of higher risk patients into ESRD programs, explain the ongoing and projected increases in the numbers of patients with ESRD. The increasing incidence and prevalence of ESRD and CKD is a global trend not just confined to the United States [6]. Although incidence rates for the United States and Japan are nearly two-fold higher than those of other industrialized nations, the rates of growth appear to be quite similar, best described by an exponential growth curve at the rate of 7.36% per year [7]. The impact of these numbers must be interpreted from

Clinical epidemiology of cardiovascular disease in chronic kidney disease prior to dialysis.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Both in dialysis and in transplant patients, CVD remains the leading cause of death. There is accumulating evidence that the increase in CVD burden is present in patients prior to dialysis, due to both conventional risk factors as well as those specific to kidney disease. Of importance is that even in patients with mild kidney disease, the risk of cardiovascular events and death is increased relative to patients without evidence of kidney disease. The new classification system proposed by the National Kidney Foundation as part of the Dialysis Outcomes Quality Initiative (DOQI) process describes the five stages of kidney disease, as well as those complications associated with chronic kidney disease (CKD), in particular cardiovascular risk factors and disease. Patients with kidney disease are deemed to be at highest cardiovascular risk. CVD, defined as the presence of either congestive heart failure (CHF), ischemic heart disease (IHD), or left ventricular hypertrophy (LVH), is prevalent in cohorts with established CKD (8-40%). The prevalence of hypertension, a major risk factor for coronary artery disease (CAD) and LVH is high in patients with CKD (87-90%). At least 35% of patients with CKD have evidence of an ischemic event (myocardial infarction or angina) at the time of presentation to a nephrologist. The prevalence of LVH increases at each stage of CKD, reaching 75% at the time of dialysis initiation, and the modifiable risk factors for LVH include anemia and systolic blood pressure, which are also worse at each stage of kidney disease. Even under the care of nephrologists, a change in cardiac status (worsening of heart failure or anginal symptoms) occurs in 20% of patients. The presence of CVD predicts a faster decline of kidney function and the need for dialysis, after controlling for all other factors including glomerular filtration rate (GFR), age, and the presence of LVH. This article describes the new classification system for staging of CKD, defines and describes CVD in CKD, and reviews the evidence and its limitations with respect to the current understanding of CKD and CVD. Specifically, methodologic issues related to survival and referral bias limit our current understanding of the complex interaction of conventional and nonconventional kidney disease-specific risk factors. We identify the importance of well-conducted studies of patient groups with and without CVD, with and without CKD, in order to better understand the complex physiology so that treatment strategies can be appropriately applied.

Clinical correlates and mortality impact of left ventricular hypertrophy among new ESRD patients in the United States

Background: Left ventricular hypertrophy (LVH) is common among patients with end-stage renal disease (ESRD), but few population-based studies exist. Here, we describe clinical correlations and mortality impact of LVH in new patients with ESRD from the Dialysis Morbidity and Mortality Study Wave 2. Methods: Echocardiographic data denoting the presence or absence of LVH were available for 64% (n = 2,584) of the entire cohort. Multivariate logistic regression identified significant correlates of LVH, and Cox proportional hazards regression estimated the mortality risk (risk ratio [RR]) for LVH at 6, 12, and 24 months. Results: The prevalence of LVH was 16.4%. Multivariate analysis identified age (adjusted odds ratio [OR], 1.15 per 10 years older), hypertension (OR, 1.39), diabetes (OR, 1.47), tobacco use (OR, 1.42), serum calcium level (OR, 1.17 per 1 mg/dL [0.25 mmol/L] higher), parathyroid hormone level greater than versus less than 157 pg/mL (157 ng/L; OR, 1.53), serum albumin level (OR, 1.38 per 1 g/dL [10 g/L] lower), and presence of pericarditis (OR, 2.55) as significant disease correlates. The impact of LVH on subsequent mortality was greatest in the first 6 months of follow-up (RR, 1.61; confidence interval [CI], 1.17 to 2.22) and became less pronounced thereafter (RR, 1.36; CI, 1.07 to 1.89; RR, 1.29; CI, 1.07 to 1.56 at the end of 1 and 2 years, respectively). Conclusion: This study identifies known coronary risk factors and markers of uremia as independent correlates of LVH presence in new patients with ESRD. It also highlights the adverse impact of pre-ESRD LVH on short-term patient survival. Given the clinical consequences of LVH on morbidity and mortality, greater efforts are required to reduce known risk factors for LVH in the pre-ESRD period. Am J Kidney Dis 40:1102-1110. © 2002 by the National Kidney Foundation, Inc.

A novel association between residual renal function and left ventricular hypertrophy in peritoneal dialysis patients

Left ventricular hypertrophy (LVH) and dialysis adequacy are both important predictors for mortality in dialysis patients. This study evaluated the association between residual renal function (RRF) and the severity of LVH in endstage renal failure (ESRF) patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD). A cross-section study was performed with left ventricular mass index (LVMi), determined in 158 non-diabetic CAPD patients using echocardiography and its relationship with residual glomerular filtration rate (GFR), peritoneal dialysis (PD) and total weekly urea clearance (Kt/V) and other known risk factors for LVH was evaluated. Twelve patients had no LVH (group I). The remaining 146 patients were stratified [group II (lowest), III and IV (highest)] according to the LVMi (median 207 g/m2; range 103 to 512 g/m2). Across the four groups of patients with increasing LVMi, there was significant decline in GFR (2.27 +/- 1.98 vs. 1.49 +/- 1.58 vs. 1.61 +/- 1.91 vs. 0.80 +/- 1.42 mL/min/1.73 m2; P = 0.011) and total weekly Kt/V (1.98 +/- 0.44 vs. 1.96 +/- 0.38 vs. 1.92 +/- 0.42 vs. 1.71 +/- 0.42; P = 0.037); however, PD Kt/V was similar for all four groups. Patients with better-preserved residual GFR not only had significantly higher total Kt/V, but were less anemic and hypoalbuminemic and had a trend toward lower systolic blood pressure and arterial pulse pressure. Multiple regression analysis showed that other than age, gender, body weight, arterial pulse pressure, hemoglobin and serum albumin, known factors for LVH, residual GFR (estimated mean -7.94; 95% confidence interval -15.13 to -0.74; P = 0.031) was also independently associated with LVMi. Other than anemia, hypoalbuminemia and arterial pulse pressure, this study demonstrates an important, novel association between the degree of RRF and severity of LVH in ESRF patients undergoing long-term CAPD. Prospective studies are needed to define if indeed there is a cause-effect relationship between this association, to evaluate if a decline in residual GFR is independently associated with an increase in LVMi, and to determine whether treatment directed at preserving RRF will reduce the severity of LVH, improve cardiac performance and hence survival of these patients.

Performance of classic electrocardiographic criteria for left ventricular hypertrophy in an African population.

ECG criteria for left ventricular hypertrophy (LVH) have been almost exclusively elaborated and calibrated in white populations. Because several interethnic differences in ECG characteristics have been found, the applicability of these criteria to African individuals remains to be demonstrated. We therefore investigated the performance of classic ECG criteria for LVH detection in an African population. Digitized 12-lead ECG tracings were obtained from 334 African individuals randomly selected from the general population of the Republic of Seychelles (Indian Ocean). Left ventricular mass was calculated with M-mode echocardiography and indexed to body height. LVH was defined by taking the 95th percentile of body height-indexed LVM values in a reference subgroup. In the entire study sample, 16 men and 15 women (prevalence 9.3%) were finally declared to have LVH, of whom 9 were of the reference subgroup. Sensitivity, specificity, accuracy, and positive and negative predictive values for LVH were calculated for 9 classic ECG criteria, and receiver operating characteristic curves were computed. We also generated a new composite time-voltage criterion with stepwise multiple linear regression: weighted time-voltage criterion=(0.2366R(aVL)+0.0551R(V5)+0.0785S(V3)+ 0.2993T(V1))xQRS duration. The Sokolow-Lyon criterion reached the highest sensitivity (61%) and the R(aVL) voltage criterion reached the highest specificity (97%) when evaluated at their traditional partition value. However, at a fixed specificity of 95%, the sensitivity of these 10 criteria ranged from 16% to 32%. Best accuracy was obtained with the R(aVL) voltage criterion and the new composite time-voltage criterion (89% for both). Positive and negative predictive values varied considerably depending on the concomitant presence of 3 clinical risk factors for LVH (hypertension, age >/=50 years, overweight). Median positive and negative predictive values of the 10 ECG criteria were 15% and 95%, respectively, for subjects with none or 1 of these risk factors compared with 63% and 76% for subjects with all of them. In conclusion, the performance of classic ECG criteria for LVH detection was largely disparate and appeared to be lower in this population of East African origin than in white subjects. A newly generated composite time-voltage criterion might provide improved performance. The predictive value of ECG criteria for LVH was considerably enhanced with the integration of information on concomitant clinical risk factors for LVH.