The association between socioeconomic disparities and left ventricular hypertrophy in chronic kidney disease: results from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).

BACKGROUND: Left ventricular hypertrophy (LVH) is one of the risk factors for cardiovascular (CV) disease and mortality. However, the relationship between socioeconomic status (SES) and LVH in chronic kidney disease remains unclear. METHODS: Data were collected from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD, NCT01630486 at http://www.clinicaltrials.gov ). Subjects with CKD and aged ≥50 were included. SES was characterized based on monthly income and educational attainment, each of which was divided into three strata. LVH was defined as LV mass/height2.7 ≥ 47 g/m2.7 in female and ≥ 50 g/m2.7 in male. Age, sex, diabetes, CKD stage, body mass index, blood pressure and physical activity were included as covariates. RESULTS: A total of 1361 patients were included. Mean age was 60.9 ± 6.9 years, and 63.2% were men. Higher education level was associated with higher monthly income (P for trend < 0.001). The lowest education level was independently associated with LVH (lower than high school, adjusted odds ratio [OR] 1.485, 95% CI 1.069-2.063, P = 0.018; completed high school, adjusted OR 1.150, 95% confidence interval [CI] 0.834-1.584, P = 0.394; highest education level as the reference). Monthly income level was marginally associated with LVH after adjusting for covariates ($1500-4500, adjusted OR 1.230, 95% CI 0.866-1.748, P = 0.247; < $1500, adjusted OR 1.471, 95% CI 1.002-2.158, P = 0.049; > $4500; reference). CONCLUSIONS: In the CKD population, lower SES, defined by educational attainment and low income level exhibited a significant association with LVH, respectively. Longitudinal follow-up will reveal whether lower SES is associated with poor CKD outcomes.

Air Pollution, Cardiovascular Outcomes, and Social Disadvantage: The Multi-ethnic Study of Atherosclerosis.

BACKGROUND: Social factors may enhance health effects of air pollution, yet empirical support is inconsistent. The interaction of social and environmental factors may only be evident with long-term exposures and outcomes that reflect long-term disease development. METHODS: We used cardiac magnetic resonance imaging data from the Multi-Ethnic Study of Atherosclerosis to assess left-ventricular mass index (LVMI) and left-ventricular ejection fraction (LVEF). We assigned residential concentrations of fine particulate matter (PM2.5), oxides of nitrogen, and nitrogen dioxide in the year 2000 to each participant in 2000 using prediction models. We examined modifying roles of four measures of adversity: race/ethnicity, racial/ethnic residential segregation, and socioeconomic status and psychosocial adversity as composite indices on the association between air pollution and LVMI or LVEF. RESULTS: Compared with whites, blacks showed a stronger adjusted association between air pollution and LVMI. For example, for each 5 µg/m greater PM2.5 level, whites showed a 1.0 g/m greater LVMI (95% confidence interval = -1.3, 3.1), while blacks showed an additional 4.0 g/m greater LVMI (95% confidence interval = 0.3, 8.2). Results were similar for oxides of nitrogen and nitrogen dioxide with regard to black race and LVMI. However, we found no evidence of a modifying role of other social factors or ethnic groups. Furthermore, we found no evidence of a modifying role for any social factors or racial/ethnic groups on the association between air pollution and LVEF. CONCLUSIONS: Our results suggest that racial group membership may modify the association between air pollution and cardiovascular disease.

Echocardiography in newly diagnosed atrial fibrillation patients: a systematic review and economic evaluation.

OBJECTIVE: To investigate the clinical effectiveness and cost-effectiveness of transthoracic echocardiography (TTE) in all patients who are newly diagnosed with atrial fibrillation (AF). DESIGN: Narrative synthesis reviews were conducted on the prognostic and diagnostic accuracy of TTE for, and prevalence of, pathologies in patients with AF. Databases were searched from inception. MEDLINE searches were conducted from March to August 2010, and reference lists of articles checked. There were 44 diagnostic accuracy studies, five prognostic studies, and 16 prevalence studies accepted into the review. Given the complexity of the many pathologies identified by TTE, the variety of potential changes to clinical management, and paucity of data, the model focused on changes to oral anticoagulation (OAC). The mathematical model assessed the cost-effectiveness of TTE for patients with AF who were not routinely given OAC, assuming, if left atrial abnormality was detected, that the higher risk of stroke warranted OAC; this meant that patients with a CHADS2 (cardiac failure, hypertension, age, diabetes, stroke doubled) score of 0 [dabigatran etexilate (Pradaxa, Boehringer Ingelheim)/rivaroxaban (Xarelto, Bayer Schering)] or 0/1 (warfarin) were included. A simplified approach evaluated the additional quality-adjusted life-years (QALYs) required in order for TTE to be perceived as cost-effective at a threshold of £20,000 per QALY. SETTING: Transthoracic echocardiography is usually performed in cardiology clinics but may be used in primary or non-specialist secondary care. PARTICIPANTS: Patients with newly diagnosed AF. INTERVENTION: Transthoracic echocardiography. MAIN OUTCOME MEASURES: Prognosis, diagnostic sensitivity or specificity of TTE, prevalence of pathologies in patients with AF, cost-effectiveness and QALYs. RESULTS: Prognostic studies indicated that TTE-diagnosed left ventricular dysfunction, increased left atrial diameter and valvular abnormality were significantly associated with an increased risk of stroke, mortality or thromboembolism. There was a high prevalence (around 25-30%) of ischaemic heart disease, valvular heart disease and heart failure in patients with AF. Diagnostic accuracy of TTE was high, with most pathologies having specificity of ≥ 0.8 and sensitivity of ≥ 0.6. The mathematical model predicted that when the CHADS2 tool is used the addition of TTE in identifying patients with left atrial abnormality appears to be cost-effective for informing some OAC decisions. In the simplified approach a threshold of 0.0033 was required for a TTE to be cost-effective. CONCLUSIONS: When CHADS2 was used, the addition of TTE in identifying patients with left atrial abnormality was cost-effective for informing some OAC decisions. A simple analysis indicates that the number of QALYs required for TTE to be cost-effective is small, and that if benefits beyond those associated with a reduction in stroke are believed probable then TTE is likely to be cost-effective in all scenarios. Our findings suggest that further research would be useful, following up newly diagnosed patients with AF who have undergone TTE, to study treatments given as a result of TTE diagnoses and subsequent cardiovascular events. This could identify additional benefits of routine testing, beyond stroke prevention. Studies assessing the proportion of people with a CHADS2 score of 0 or 1 that have left atrial abnormality would provide better estimates of the cost-effectiveness of TTE, and allow more accurate estimates of the sensitivity and specificity of TTE for identifying left atrial abnormality in AF to be obtained. STUDY REGISTRATION: PROSPERO CRD42011001354. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of electrocardiography vs. electrocardiography plus limited echocardiography to diagnose LVH in young, newly identified, hypertensives.

BACKGROUND: In the United States, screening for left ventricular hypertrophy (LVH) in a newly diagnosed hypertensive patient is typically performed using electrocardiography (ECG). Echocardiography (echo) is a more accurate but also more expensive procedure. However, the introduction of limited echo within the past decade has made sonographic imaging of the heart less expensive and more available for routine screening. METHODS: The cost per additional correct diagnosis of LVH for ECG vs. ECG plus limited echo (with limited echo utilized in patients without ECG evidence of LVH) was analyzed using decision analytic modeling. A structured literature search was used to parameterize model probabilities, and costs are based on the 2008 Medicare Physician Fee Schedule. The study population consisted of black and white cohorts ~50 years of age with new diagnosis of hypertension. Outcomes included short-term results of LVH screening and diagnosis, and the study perspective was health system. RESULTS: Base-case results indicate each additional correct LVH diagnosis by ECG plus limited echocardiography instead of ECG cost $655 in the black cohort and $829 in the white cohort. Results in both cohorts were most sensitive to the cost of echocardiography. Simulation-generated cost-effectiveness acceptability curves demonstrated costs per additional correct diagnosis have a 90% likelihood of being below $993 and $1,420 in the black and white cohorts, respectively. CONCLUSIONS: LVH detection by ECG plus limited echocardiography may be an economically feasible alternative to ECG due to increased accuracy. However, final recommendations require analysis of long-term effects on morbidity, mortality, quality of life, and subsequent treatment costs between the diagnostic approaches.

Left ventricular hypertrophy and clinical outcomes in hypertensive patients.

The prevalence of left ventricular hypertrophy (LVH) rises with severity of hypertension (HT), age, and obesity. Its prevalence ranges from 20% in mildly hypertensive patients to almost 100% in those with severe or complicated HT. However, the diagnosis of LVH is not straightforward, and the definitions and criteria used in clinical studies lack consistency. While many factors play a role in the onset and progression of LVH, blood pressure (BP) is recognized as a central factor. Twenty-four-hour BP measurements are more closely related to LVH than conventional BP readings taken in the clinician's office. Increased renin-angiotensin system (RAS) activity also plays an important role in the development of LVH, and various studies show a correlation between plasma renin activity and left ventricular mass (LVM). LVH is a recognized marker of HT-related target organ damage, and a strong and independent risk factor for adverse cardiovascular (CV) outcomes. CV risk increases with increasing LVM, and decreases with regression of LVH in response to antihypertensive treatment. Therefore the detection, prevention, and reversal of LVH are important goals in HT management. Most antihypertensive drugs can attenuate BP and LVH. However, each drug class may induce LVH regression to a different extent and these extents seldom correlate with the degree of BP reduction achieved. Data from the few large comparative studies in this area suggest that certain classes of antihypertensive drugs and/or their combinations are more effective than others. In particular, calcium channel blockers and drugs that target the RAS, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), appear to have a specific effect on LVH, independent of BP reduction. Guidelines, therefore, have recommended these drug classes for the treatment of hypertensive patients with LVH.

Left ventricular hypertrophy and cardiovascular risk stratification: impact and cost-effectiveness of echocardiography in recently diagnosed essential hypertensives.

BACKGROUND: Echocardiography is more accurate than electrocardiography in the assessment of cardiac target organ damage related to hypertension, thus leading to a more precise stratification of total cardiovascular risk. However, ultrasound examination of the heart on a routine basis remains a matter of debate. OBJECTIVE: To evaluate the impact and cost-effectiveness of echocardiographic examination on global risk stratification in low and medium-risk hypertensive patients in relation to age and sex. METHODS: A total of 580 untreated hypertensive individuals (355 men and 225 women, mean age 47.8 +/- 11.4 years), classified at low to medium risk, according to routine clinical work-up suggested by the 2003 European Society of Hypertension/European Society of Cardiology guidelines, were included in the study. Total risk was reassessed by adding the results of ultrasound examination of the heart. Left ventricular hypertrophy (LVH) was defined as a left ventricular mass index of 125 g/m2 or more in men and 110 g/m2 or more in women. The impact of LVH in stratifying risk was assessed according to age (< 50 and > or = 50 years) and sex. RESULTS: According to routine classification, 16.3% (n = 93) of the 580 patients were considered to be at low added risk and 83.7% (n = 487) at medium added risk. In the whole population, echocardiographic LVH was found in 86 patients (14.8%) who were then reclassified in the high-risk stratum. The prevalence rates of patients reclassified in the high-risk class as a consequence of LVH detection, according to age and sex, were as follows: 8.9% in men under 50 years, 12.3% in women under 50 years, 26.7% in men aged 50 years and over and 15.3% in women aged 50 years and over. The cost per detected case of LVH was 595 euros in patients under 50 years of age and 290 euros in those 50 years of age and older. CONCLUSIONS: Our findings indicate that the prevalence of LVH, and consequently the probability of upgrading the total cardiovascular risk profile, is highest in the group of old hypertensive men; echocardiography has a limited impact on the risk reclassification in younger patients and an unfavourable cost-effectiveness profile. Our data thus do not support the systematic ultrasound assessment of the heart in all uncomplicated hypertensive individuals.

A cost-utility analysis of losartan versus atenolol in the treatment of hypertension with left ventricular hypertrophy.

INTRODUCTION: The LIFE (Losartan Intervention For Endpoint reduction in hypertension) study demonstrated a 13% relative risk reduction in the primary composite endpoint (myocardial infarction, stroke or death) for patients with hypertension and electrocardiographically diagnosed left ventricular hypertrophy (LVH) treated with losartan compared with atenolol. Losartan recipients also had a 25% relative risk reduction for stroke compared with atenolol recipients. Incorporating the results found in the LIFE study into an economic model, an incremental cost-effectiveness analysis was performed comparing losartan with atenolol in the treatment of 67-year old patients with hypertension and LVH. METHODS: A Markov state transition model, based on published results of the LIFE trial (mean follow-up of 4.8 years), was utilised to extrapolate the outcomes observed in this trial to the patients' lifetime. Utility estimates for the associated health states were obtained from various published sources. Lifetime treatment costs were calculated adopting a societal perspective. Both costs and benefits were discounted and incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed. RESULTS: The estimated ICER for losartan versus atenolol was 1337 Canadian dollars per QALY gained (1 Canadian dollar =0.75 US dollars, 2002 values). This ICER was robust to extensive sensitivity analysis, demonstrating a 95% probability that the ICER would be <20,000 Canadian dollars per QALY gained. CONCLUSION: From a Canadian societal perspective, losartan appears to be a cost-effective alternative to atenolol in patients with hypertension and LVH. The estimated ICERs, including the sensitivity analyses, were within the range of cost-effectiveness ratios for various currently funded interventions and drugs in developed countries.

Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study.

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study demonstrated the clinical benefit of losartan-based therapy in hypertensive patients with left ventricular hypertrophy (LVH), mainly due to a highly significant 25% reduction in the relative risk of stroke compared with an atenolol-based regimen, for a similar reduction in blood pressure. The aim of this economic evaluation was to estimate the cost-effectiveness of losartan compared with atenolol from a UK national health system perspective. Quality-adjusted survival and direct medical costs were modelled beyond the trial using the within-trial incidence of stroke. Survival with stroke, study medication use and quality of life by stroke status were taken directly from the LIFE trial. The LIFE data were supplemented with UK data on lifetime direct medical costs of stroke and life expectancy in individuals without stroke. No additional stroke events or use of study treatment were assumed beyond the trial. Costs and benefits were discounted using current UK Treasury rates. In the base-case analysis, the reduction in stroke-related costs (by 968 sterling pound) offset 86% of the increase in study medication costs (1128 sterling pound) among losartan-treated patients. The incremental cost-effectiveness ratio (ICER) for losartan versus atenolol in hypertensive patients with LVH was 2130 sterling pound per quality-adjusted life year (QALY) gained (3195 Euro/QALY), and this increased to 11,352 sterling pound per QALY gained (16,450 Euro/QALY) when the costs of stroke beyond the first 5 years were excluded. Thus, the clinical benefit of losartan was achieved at a cost well within reported thresholds for cost-effectiveness.

Cost effectiveness of losartan in patients with hypertension and LVH: an economic evaluation for Sweden of the LIFE trial.

OBJECTIVE: Evaluate the cost effectiveness of losartan compared with atenolol from a Swedish national health system perspective. DESIGN: The Losartan Intervention For Endpoint reduction in hypertension study (LIFE) was a double-masked, randomized trial of losartan versus atenolol in 9193 patients with essential hypertension and left ventricular hypertrophy (LVH) ascertained by electrocardiography. Losartan reduced the primary composite end point of cardiovascular death, myocardial infarction (MI), or stroke by 13% (P = 0.021) and reduced the risk of stroke by 25% (P = 0.001), despite a comparable degree of blood pressure control. METHODS: Life years gained was estimated by combining the absolute risk reduction in stroke with the life years gained by preventing stroke. Quality-adjusted life years (QALYs) gained was estimated by combining the absolute risk reduction in stroke with the QALYs gained by preventing stroke. QALYs were estimated by weighting life years by health-related quality of life (QoL), as measured with visual analogue scale (VAS) data collected in the trial. Net costs were defined as the total of study medication cost, stroke-related costs, and costs of increased survival. Costs are in 2003 Swedish prices. All costs and effects were discounted at a 3% annual rate. RESULTS: Prevention of a stroke resulted in a gain of 5.7 life years and 4.3 QALYs. As a consequence, losartan treatment resulted in a per patient increase of 0.092 life years [95% confidence interval (CI): 0.038, 0.146] and 0.069 QALYs (95% CI: 0.028, 0.109) as compared with atenolol treatment. Losartan reduced direct stroke-related cost per patient by 1141 euros due to a lower cumulative incidence of stroke for losartan at 5.5 years (4.9%) as compared with atenolol (6.5%) (95% CI of difference: 0.7, 2.5). The reduction in stroke-related cost offset 80% of the added cost of losartan drug therapy. After inclusion of study medication cost, net cost per patient was 289 euros higher for losartan than atenolol. The net cost per QALY gained for losartan was 4188 euros (37,813 SEK), which is well within common Swedish benchmark upper values (200-500,000 SEK) for accepted cost-effective interventions. CONCLUSION: Based on the results from the LIFE trial, treatment with losartan compared with atenolol, in hypertensive patients with LVH, is a cost-effective intervention.

Optimizing global risk evaluation in primary hypertension: the role of microalbuminuria and cardiovascular ultrasonography.

OBJECTIVE: To assess the impact and cost-effectiveness of microalbuminuria and cardiovascular ultrasonography in evaluating the risk profile in primary hypertension. METHODS: Four hundred and five untreated patients with primary hypertension underwent a routine, traditional work-up plus evaluation of albuminuria and ultrasound (US) assessment of cardiac and vascular structures. Albuminuria was measured as the albumin to creatinine ratio in three non-consecutive first-morning urine samples. Left ventricular mass index was assessed by MB-mode echocardiography and carotid intima-media thickness by high-resolution US scan. The impact of these tests on patient risk classes, as indicated by European Society of Hypertension-European Society of Cardiology (ESH-ESC) guidelines, was assessed with respect to their cost and sensitivity. RESULTS: The prevalence of microalbuminuria, left ventricular hypertrophy and carotid intima-media thickening or carotid plaque was 13, 49 and 32%, respectively. The combined use of albuminuria, cardiac and vascular ultrasonography led to the detection of a significantly higher percentage of patients at high/very high risk. The three tests differ in sensitivity (albuminuria, 20%; echocardiography, 65%; and carotid ultrasound, 41%). The signs of target organ damage (TOD) only partly cluster within the same subgroup of patients and, thus, all three tests should be performed in order to maximize the sensitivity of the evaluation process. The diagnostic algorithm yielding the lowest cost per detected case of TOD is the search for microalbuminuria followed by cardiac and carotid ultrasound assessment. CONCLUSIONS: Ultrasonographic detection of TOD is a sensitive tool in the identification of high-risk patients, but should be preceded by a routine search for microalbuminuria in order to optimize the cost-effectiveness of the diagnostic work-up.

Hypothetical economic analysis of screening for left ventricular hypertrophy in high-risk normotensive populations.

BACKGROUND: Left ventricular hypertrophy (LVH) measured by echocardiography is a powerful independent marker of increased cardiovascular risk. The prevalence of echocardiographic LVH in patients with high cardiovascular risk appears to be high, even in patients currently considered normotensive. AIM: To ascertain the likely costs of screening for and treating echocardiographic LVH in normotensive patients at high risk of cardiovascular events. DESIGN: Hypothetical economic analysis. METHODS: Cost analyses were based on known costs of echocardiography, costs of selected cardiovascular medications and prevalence of normotensive LVH in at-risk populations, combined with treatment effect data from studies of hypertensive patients with echocardiographic LVH. RESULTS: Screening costs per case for echocardiographic LVH are likely to be low, because of the high prevalence of the condition and the low unit cost of echocardiography. Treatment costs are likely to be comparable to those currently deemed acceptable in treating high-risk cardiovascular populations, e.g. the HOPE study population. DISCUSSION: The costs of screening for and treating LVH in normotensive patients at risk of cardiovascular events do not appear to be prohibitively high. Trials of screening and treatment for normotensive LVH seem therefore to be warranted.

The cost effectiveness of ACE inhibitors as first-line antihypertensive therapy.

BACKGROUND: Current hypertension guidelines differ in their recommendations for first-line antihypertensive therapy. OBJECTIVE: To evaluate the cost effectiveness of ACE inhibitor therapy as antihypertensive first-line therapy as compared with conventional antihypertensive therapy with beta-adrenoceptor antagonists or diuretics. STUDY DESIGN: Cost-effectiveness analysis based on data from randomised trials and observational studies comparing the effectiveness of ACE inhibitor and conventional antihypertensive therapy, we constructed a Markov model to compare four strategies in the management of uncomplicated hypertension: (i) prescribing ACE inhibitor therapy to all patients; (ii) prescribing conventional therapy to all patients; (iii) individualised antihypertensive therapy based on the presence or absence of left ventricular hypertrophy on electrocardiography (ECG); or (iv) individualised antihypertensive therapy based on the presence or absence of left ventricular hypertrophy on echocardiography. METHODS: Cost data were derived from the medical literature and focus groups, and utility values were derived from patients on antihypertensive monotherapy. All costs were calculated in 1999 Canadian dollars, but are reported in US dollars according to the 1999 purchasing power parity rate for medical and healthcare. The effectiveness of ACE inhibitor therapy in the presence of left ventricular hypertrophy was derived from observational studies. The time horizon was over a lifetime. PERSPECTIVE: Third-party payer. PATIENTS/PARTICIPANTS: A cohort of men aged 40 years without cardiovascular comorbidity requiring antihypertensive drug therapy. MAIN OUTCOME MEASURES AND RESULTS: In the baseline analysis, all four strategies resulted in expected discounted QALYs that differed from each other only at the third decimal point (i.e. less than 0.003). Given the uncertainties in the variable estimates and the small size of the differences, these differences are extremely small and unlikely to represent real differences. Even accepting the small gains as real, the resulting cost-effectiveness ratios are unattractively high: $US 200,000 per QALY gained for the echocardiography strategy (compared with ECG), and $US 700,000 for the "ACE inhibitor for all" strategy (compared with ECG). The incremental cost effectiveness of prescribing ACE inhibitor therapy to everybody was never less than $US 100,000/QALY in the sensitivity analysis. CONCLUSIONS: Prescribing ACE inhibitors as antihypertensive first-line therapy in patients without cardiovascular morbidity cannot be recommended at the present time unless the acquisition costs of ACE inhibitors become substantially more attractive.

Echocardiography for primary care evaluation of hypertension.

OBJECTIVE: To reexamine the changing role of echocardiography for primary care evaluation of essential hypertension since the 1993 Canadian Hypertension Society Consensus Conference. QUALITY OF EVIDENCE: New recommendations from the Canadian Cardiovascular Society and the Canadian Hypertension Society. Recommendations from the American College of Cardiology based on a prospective, randomized controlled trial of limited echocardiograms. Further results from the Framingham Heart Study and the Treatment of Mild Hypertension Study. MAIN MESSAGE: For patients with essential hypertension, left ventricular hypertrophy (LVH) continues to be a strong predictor of many cardiovascular end points, and echocardiography is a much more sensitive tool for detecting LVH than electrocardiogram (ECG). Although limited echocardiograms are not usually used, they are a less costly method of evaluating LVH than standard echocardiograms and have recently been recommended in the United States to assist in the decision to initiate pharmacotherapy for patients with stage 1 hypertension and no other evidence of target organ damage. Problems with intrareader and interreader variability of results are being addressed by technical and mathematical standards established by the Canadian Cardiovascular Society and the Canadian Hypertension Society. CONCLUSIONS: Using limited echocardiograms for assessing LVH coupled with implementing Canadian technical standards might lead to a greater role for echocardiography in evaluating essential hypertension in certain patients.