In-treatment HDL cholesterol levels and development of new diabetes mellitus in hypertensive patients: the LIFE Study.

AIMS: Although hypertensive patients with low baseline HDL cholesterol levels have a higher incidence of diabetes mellitus, whether changing levels of HDL over time are more strongly related to the risk of new diabetes in hypertensive patients has not been examined. METHODS: Incident diabetes mellitus was examined in relation to baseline and in-treatment HDL levels in 7485 hypertensive patients with no history of diabetes randomly assigned to losartan- or atenolol-based treatment. RESULTS: During 4.7 ± 1.2 years follow-up, 520 patients (6.9%) developed new diabetes. In univariate Cox analyses, compared with the highest quartile of HDL levels (> 1.78 mmol/l), baseline and in-treatment HDL in the lowest quartile (< 1.21 mmol/l) identified patients with > 5-fold and > 9 fold higher risks of new diabetes, respectively; patients with baseline or in-treatment HDL in the 2nd and 3rd quartiles had intermediate risk of diabetes. In multivariable Cox analyses, adjusting for randomized treatment, age, sex, race, prior anti-hypertensive therapy, baseline uric acid, serum creatinine and glucose entered as standard covariates, and in-treatment non-HDL cholesterol, Cornell product left ventricular hypertrophy, diastolic and systolic pressure, BMI, hydrochlorothiazide and statin use as time-varying covariates, the lowest quartile of in-treatment HDL remained associated with a nearly 9-fold increased risk of new diabetes (hazard ratio 8.7, 95% CI 5.0-15.2), whereas the risk of new diabetes was significantly attenuated for baseline HDL < 1.21 mmol/l (hazard ratio 3.9, 95% CI 2.8-5.4). CONCLUSIONS: Lower in-treatment HDL is more strongly associated with increased risk of new diabetes than baseline HDL level.

Impact of overweight and obesity on cardiac benefit of antihypertensive treatment.

BACKGROUND AND AIMS: Increased body mass index (BMI) has been associated with increased cardiovascular morbidity and mortality in hypertension. Less is known about the impact of BMI on improvement in left ventricular (LV) structure and function during antihypertensive treatment. METHODS AND RESULTS: Annual BMI, echocardiograms and cardiovascular events were recorded in 875 hypertensive patients with LV hypertrophy during 4.8 years randomized treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy. Patients were grouped by baseline BMI into normal (n = 282), overweight (n = 405), obese (n = 150) and severely obese groups (n = 38) (BMI ≤24.9, 25.0-29.9, 30.0-34.9, and ≥35.0 kg/m(2), respectively). At study end, residual LV hypertrophy was present in 54% of obese and 79% of severely obese patients compared to 31% of normal weight patients (both p < 0.01). In regression analyses, adjusting for initial LV mass/height(2.7), higher BMI predicted less LV hypertrophy reduction and more reduction in LV ejection fraction (both p < 0.05), independent of blood pressure reduction, diabetes and in-study weight change. During follow-up, 91 patients suffered cardiovascular death, myocardial infarction or stroke. In Cox regression analysis 1 kg/m(2) higher baseline BMI predicted a 5% higher rate of cardiovascular events and 10% higher cardiovascular mortality over 4.8 years (both p < 0.05). CONCLUSIONS: In hypertensive patients in the LIFE study, increased BMI was associated with less reduction of LV hypertrophy and less improvement in LV systolic function which may contribute to the observed higher cardiovascular event rate of treated hypertensive patients.

Early combination therapy with telmisartan plus amlodipine for rapid achievement of blood pressure goals.

BACKGROUND: Rapid and sustained blood pressure (BP) goal attainment is important to reduce cardiovascular risk. Initial use of combination therapy may improve BP goal attainment. METHODS: The Boehringer Ingelheim trial database was searched for randomised, double-blind studies comparing telmisartan/amlodipine combination therapy with monotherapy. Eight studies were identified. Eight separate analyses were used to compare combination therapy with respective monotherapies at the earliest available time points (weeks 1, 2 and/or 4). RESULTS: In patients initiated on combination therapy, greater systolic BP (SBP)/diastolic BP (DBP) reductions were seen with combination therapy (p < 0.0001); BP (< 140/90 mmHg), SBP (< 140 mmHg) and DBP (< 90 mmHg) goal attainment rates were significantly higher with combination therapy at all time points. In patients uncontrolled by monotherapy, greater SBP/DBP reductions were seen with combination therapy (p < 0.05 in all but one measure), and all goal attainment rates were significantly higher with combination therapy, except in one measure. CONCLUSION: Many people can achieve their BP targets when taking a combination of telmisartan and amlodipine after failing to do so with monotherapy. Furthermore, BP targets can be achieved more rapidly using a combination of telmisartan and amlodipine as initial therapy than with either monotherapy.

Metabolic syndrome, impaired fasting glucose and obesity, as predictors of incident diabetes in 14 120 hypertensive patients of ASCOT-BPLA: comparison of their relative predictability using a novel approach.

AIMS: To evaluate, in hypertensive patients, whether the metabolic syndrome is a better predictor of new-onset diabetes compared with impaired fasting glucose, obesity or its other individual components alone, or collectively. METHODS: Cox models were developed to assess the risk of new-onset diabetes associated with the metabolic syndrome after adjusting for a priori confounders (age, sex, ethnicity and concomitant use of non-cardiovascular medications), its individual components and other determinants of new-onset diabetes. Area under receiver operator curves using the metabolic syndrome or models of impaired fasting glucose were compared, and the ability of these models to correctly identify those who (after 5-years of follow-up) would or would not develop diabetes was assessed. RESULTS: The metabolic syndrome adjusted for a priori confounders and its individual components, and further adjusted for other determinants, was associated with significantly increased risk of new-onset diabetes [1.19 (1.00-1.40), P = 0.05 and 1.22 (1.03-1.44), P = 0.02, respectively]. The discriminative ability of the metabolic syndrome model [area under receiver operating curve: 0.764 (0.750-0.778)] was significantly better than the model of impaired fasting glucose [0.742 (0.727-0.757)] (P < 0.001). The metabolic syndrome correctly allocates the risk of new-onset diabetes in a significantly higher proportion of patients (62.3%) than impaired fasting glucose status (37.7%) (P < 0.001). The presence of both the metabolic syndrome and impaired fasting glucose were associated with an approximately 9-fold (7.47-10.45) increased risk of new-onset diabetes. Among normoglycaemic patients, the metabolic syndrome was also associated with significantly increased risk of new-onset diabetes, after adjusting for BMI and a priori confounders [1.66 (1.29-2.13)]. CONCLUSIONS: Both impaired fasting glucose and the metabolic syndrome predict the risk of new-onset diabetes; however, the metabolic syndrome is a better predictor than impaired fasting glucose in assigning the risk of new-onset diabetes in hypertensive patients, and among those with normoglycaemia.

The economic consequences of non-adherence to lipid-lowering therapy: results from the Anglo-Scandinavian-Cardiac Outcomes Trial.

BACKGROUND: Adherence to lipid-lowering therapy in clinical practice is less than ideal. Analysis of registry data has indicated that this is associated with poor outcomes. The objective of the present analysis was to assess the impact of high adherence to drug (defined as > 80% of days covered), compared with low adherence to drug (< 50% of days covered) in terms of risk of events and long-term economic consequences. DESIGN: Open-label follow up of a randomised placebo-controlled trial in hypertensive patients. METHODS: Cox proportional hazards and Poisson regression models were used to assess the hazard ratio of patients with high adherence compared with low adherence while controlling for cardiovascular risk. A Markov model was used to predict the long-term costs and health outcomes associated with poor adherence during the follow-up period. RESULTS: Both statistical models indicated that high adherence is associated with improved prognosis [Cox model: 0.75; 95% confidence interval (CI): 0.56-0.98, Poisson model hazard ratio: 0.73; 95% CI: 0.58-0.98]. Discounted at 3.5% per year, the Markov model predicts that as a consequence of higher adherence during the follow-up period, costs would be higher (1689 pounds per patient compared with 1323 pounds per patient) because of higher drug costs, but the projected survival and quality-adjusted survival (QALY) would also be longer (10.83 compared with 10.81 life years and 8.13 compared with 8.11 QALYs). CONCLUSION: Given the higher risk of cardiovascular events associated with low adherence shown here, measures to improve adherence are an important part of the prevention of cardiovascular disease.

Management of cardiovascular risk with RAS inhibitor/CCB combination therapy.

Hypertension is a significant risk factor for cardiovascular disease (CVD), including stroke, myocardial infarction, kidney disease and heart failure. Considerable research has been undertaken to delineate the differential effects of various classes of antihypertensive agents in delaying or preventing cardiovascular morbidity and mortality. Although possible benefits may result from specific agents or classes of agents in certain high-risk subgroups, prompt and intensive blood pressure (BP) reduction to target levels remains the most crucial factor in this benefit. Despite this, the BP remains above the target level in a large majority of patients, reinforcing the need for improved treatment paradigms. Among antihypertensive agents, inhibitors of the renin-angiotensin system--angiotensin-II receptor blockers and angiotensin-converting enzyme inhibitors--and long-acting dihydropyridine calcium channel blockers (DHP-CCBs) have been shown to provide safe, effective and well-tolerated BP control. These agents have also been proven as effective as, and in some cases superior to, other classes of agents in reducing cardiovascular morbidity and mortality. As the majority of high-risk patients require at least two and possibly even three medications to achieve the target BP, combination therapy with these two classes of drugs is a rational approach to therapy. Whether fixed-dose combination therapy with a renin-angiotensin system inhibitor plus a DHP-CCB affords greater clinical benefit compared with other combination regimens remains to be determined in large, prospective clinical trials. Meanwhile, such a combination offers effective, convenient, well-tolerated control of the most important modifiable risk factor for CVD.

Rationale and design of the KYOTO HEART study: effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high risk of cardiovascular events.

It remains to be determined whether the evidence in Western countries for blockade of the renin-angiotensin System in cardiovascular diseases could be directly applied to East Asian races including the Japanese population as a long-term strategy. The KYOTO HEART Study (KHS) is designed to investigate the add-on effect of valsartan versus conventional anti-hypertensive treatment on cardiovascular morbidity and mortality in Japanese hypertensive patients with uncontrolled blood pressure and with high cardiovascular risk. Over 3000 high-risk Japanese patients with uncontrolled hypertension were randomised to receive either additional treatment with valsartan or conventional non-angiotensin receptor blocker therapies, and the follow-up period will be at least 3 years. The primary end point is a composite of defined cardio- or cerebro-vascular events. Secondary end points include all causes of mortality, worsening of cardiac function, new onset or worsening of arrhythmias or diabetes mellitus. The KHS will provide new evidence for the management of blood pressure in hypertensive patients with high risk.

Impact of diabetes on treatment-induced changes in left ventricular structure and function in hypertensive patients with left ventricular hypertrophy. The LIFE study.

BACKGROUND AND AIM: Diabetes is associated with left ventricular hypertrophy (LVH) and impaired systolic function in hypertensive patients, but less is known about its impact on LVH regression and functional improvement during antihypertensive treatment. METHODS AND RESULTS: We performed annual echocardiography in 730 non-diabetic and 93 diabetic patients (aged 55-80 years) with hypertension and electrocardiographic LVH during 4.8-year losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Baseline mean blood pressure (BP) and LV mass did not differ between groups. Diabetic patients had higher body mass index and pulse pressure, and lower LV ejection fraction, midwall shortening, stress-corrected midwall shortening, and estimated glomerular filtration rate (all p<0.05), and were more likely to have albuminuria. Despite comparable BP reduction in diabetic and non-diabetic groups during treatment (33/18 vs. 28/16mmHg (ns)), diabetes was associated with higher prevalence of persistent LVH (47 vs. 39%, p<0.05). In multivariate analyses, diabetes independently predicted less LV mass reduction and less improvement in stress-corrected LV midwall shortening (both p<0.01). CONCLUSION: Among hypertensive patients with LVH, diabetes is associated with more residual LVH and less improvement in systolic LV function by echocardiography over 4.8 years of antihypertensive treatment.

Clustered metabolic abnormalities blunt regression of hypertensive left ventricular hypertrophy: the LIFE study.

BACKGROUND AND AIMS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two or more metabolic abnormalities (MetAb, including obesity, high plasma glucose without diabetes, low HDL-cholesterol) in addition to hypertension were associated to levels of ECG LVH reduction comparable to that obtained in hypertensive subjects without or with only one additional metabolic abnormality (no-MetAb). METHODS AND RESULTS: We studied 5558 non-diabetic participants without MetAb (2920 women) and 1235 with MetAb (751 women) from the LIFE-study cohort. MetAb was defined by reported LIFE criteria, using partition values from the ATPIII recommendations. Time-trends of Cornell voltage-duration product (CP) over 5 years was assessed using a quadratic polynomial contrast, adjusting for age, sex, prevalent cardiovascular disease and treatment arm (losartan or atenolol). At baseline, despite similar blood pressures, CP was greater in the presence than in the absence of MetAb (p<0.0001). During follow-up, despite similar reduction of blood pressure, CP decreased less in patients with than in those without MetAb, even after adjustment for the respective baseline values (both p<0.002). Losartan was more effective than atenolol in reducing CP independently of MetAb. CONCLUSIONS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome are related to greater initial ECG LVH in hypertensive patients with value of blood pressure similar to individuals without metabolic abnormalities, and are associated with less reduction of ECG LVH during antihypertensive therapy, potentially contributing to the reported adverse prognosis of metabolic syndrome.

Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study.

The relation of metabolic syndrome (MetS) with cardiovascular outcome may be less evident when preclinical cardiovascular disease is present. We explored, in a post hoc analysis, whether MetS predicts cardiovascular events in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. MetS was defined by >or=2 risk factors plus hypertension: body mass index >or=30 kg/m(2), high-density lipoprotein (HDL)-cholesterol <1.0/1.3 mmol/l (<40/50 mg/dl) (men/women), glucose >or=6.1 mmol/l (>or=110 mg/dl) fasting or >or=7.8 mmol/l (>or=140 mg/dl) nonfasting or diabetes. Cardiovascular death and the primary composite end point (CEP) of cardiovascular death, stroke and myocardial infarction were examined. In MetS (1,591 (19.3%) of 8,243 eligible patients), low HDL-cholesterol (72%), obesity (77%) and impaired glucose (73%) were similarly prevalent, with higher blood pressure, serum creatinine and Cornell product, but lower Sokolow-Lyon voltage (all P<0.001). After adjusting for baseline covariates, hazard ratios for CEPs and cardiovascular death (4.8+/-1.1 years follow-up) were 1.47 (95% confidence interval (CI), 1.27-1.71)- and 1.73 (95% CI, 1.38-2.17)-fold higher with MetS (both P<0.0001), and were only marginally reduced when further adjusted for diabetes, obesity, low HDL-cholesterol, non-HDL-cholesterol, pulse pressure and in-treatment systolic blood pressure and heart rate. Thus, MetS is associated with increased cardiovascular events in hypertensive patients with ECG-LVH, independently of single cardiovascular risk factors.

Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial.

BACKGROUND: The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) study was designed to test whether enalapril achieves greater left ventricular (LV) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis (10 g/m(2)). METHODS AND RESULTS: An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month randomized therapy. Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure (-22/12 versus -21/13 mm Hg) and LV mass index (-15 versus -17g/m(2), both P>0.20). No significant between-treatment difference was detected in population subsets defined by monotherapy treatment, sex, age, race, or severity of baseline hypertrophy. Similarly, there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow. More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide (59% versus 34%, P<0.001) but not atenolol (27% versus 22%, NS). CONCLUSIONS: Once-daily antihypertensive treatment with enalapril or long-acting nifedipine, plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure, both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy.

Reliability of echocardiographic assessment of left ventricular structure and function: the PRESERVE study. Prospective Randomized Study Evaluating Regression of Ventricular Enlargement.

OBJECTIVES: The study was done to evaluate reliability of echocardiographic left ventricular (LV) mass. BACKGROUND: Echocardiographic estimation of LV mass is affected by several sources of variability. METHODS: We assessed intrapatient reliability of LV mass measurements in 183 hypertensive patients (68% men, 65 +/- 9 years) enrolled in the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) trial after a screening echocardiogram (ECHO) showed LV hypertrophy. A second ECHO was repeated at randomization (45 +/- 25 days later). Two-dimensional (2D)-guided M-mode or 2D linear measurements of LV cavity and wall dimensions were verified by one experienced reader. RESULTS: Mean LV mass was similar at first and second ECHO (243 +/- 53 vs. 241 +/- 54 g) and showed high reliability as estimated by intraclass correlation coefficient (RHO) = 0.93. Within-patient 5th, 10th, 90th and 95th percentiles of between-study difference in LV mass were -32 g, -28 g, +25 g and +35 g. Mean LV mass fell less from the first to the second ECHO than expected from a formula to predict regression to the mean (2 +/- 19 vs. 17 +/- 12 g, p < 0.001). Reliability was also high for LV internal diameter (RHO = 0.87), septal (RHO = 0.85) and posterior wall thickness (RHO = 0.83). Substantial or moderate reliability was observed for measures of LV systolic function and diastolic filling (RHO from 0.71 to 0.57). CONCLUSIONS: Left ventricular mass had high reliability and little regression to the mean; between-study LV mass change of +/-35 g or +/-17 g had > or = 95% or > or = 80% likelihood of being true change.

Relationship of the electrocardiographic strain pattern to left ventricular structure and function in hypertensive patients: the LIFE study. Losartan Intervention For End point.

OBJECTIVES: This study was designed to assess the relation of electrocardiographic (ECG) strain to increased left ventricular (LV) mass, independent of its relation to coronary heart disease (CHD). BACKGROUND: The classic ECG strain pattern, ST depression and T-wave inversion, is a marker for left ventricular hypertrophy (LVH) and adverse prognosis. However, the independence of the relation of strain to increased LV mass from its relation to CHD has not been extensively examined. METHODS: Electrocardiograms and echocardiograms were examined at study baseline in 886 hypertensive patients with ECG LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage enrolled in the Losartan Intervention For End point (LIFE) echocardiographic substudy. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite to the QRS axis in leads V5 and/or V6. RESULTS: Strain occurred in 15% of patients, more commonly in patients with than without evident CHD (29%, 51/175 vs. 11%, 81/711, p < 0.001). When differences in gender, race, diabetes, systolic pressure, serum creatinine and high density lipoprotein cholesterol were controlled, strain on baseline ECG was associated with greater indexed LV mass in patients with (152 +/- 33 vs. 131 +/- 32 g/m2, p < 0.001) or without CHD (131 +/- 24 vs. 119 +/- 22 g/m2, p < 0.001). In logistic regression analyses, strain was associated with an increased risk of anatomic LVH in patients with CHD (relative risk 5.14, 95% confidence interval [CI] 1.16 to 22.85, p = 0.0315), without evident CHD (relative risk 2.91, 95% CI 1.50 to 5.65, p = 0.0016), and in the overall population when CHD was taken into account (relative risk 2.98, 95% CI 1.65 to 5.38, p = 0.0003). CONCLUSIONS: When clinical evidence of CHD is accounted for, ECG strain is likely to indicate the presence of anatomic LVH. Greater LV mass and higher prevalence of LVH in patients with strain offer insights into the known association of the strain pattern with adverse outcomes.

Further evidence for low-dose combinations in patients with left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is a powerful independent risk predictor for cardiovascular disease and reversal of LVH has become a primary goal of antihypertensive management. Recent evidence has confirmed that most hypertensive patients will benefit from a low-dose combination strategy to manage their hypertension, and two trials have recently examined the effect of this strategy on left ventricular mass. The REASON study (pREterax in regression of Arterial Stiffness in a contrOlled double-bliNd study) compared the low-dose combination of an angiotensin-converting enzyme (ACE) inhibitor and a diuretic with beta-blocker monotherapy in hypertensive patients with LVH, and the PICXEL study (Preterax In a double-blind Controlled study versus Enalapril in LVH) compared the same low-dose combination with ACE inhibitor monotherapy in hypertensive patients with echocardiographic LVH. The REASON study demonstrated that the low-dose combination produced a significantly greater change in left ventricular mass after 1 year than the beta-blocker, despite inducing a similar change in mean blood pressure. Additionally, perindopril/indapamide reduced central (carotid) and peripheral (brachial) systolic blood pressure (SBP) and pulse pressure (PP) to a significantly greater extent than beta-blocker, and these benefits were more pronounced for the central values; LVH is affected more by central rather than peripheral haemodynamic changes. Results of the analysis of the PICXEL study showed a significantly greater decrease in LVH parameters and blood pressure over 1 year in favour of the low-dose combination. This reduction cannot be entirely explained by the better efficacy of the low-dose combination on blood pressure reduction.

Effect of obesity on electrocardiographic left ventricular hypertrophy in hypertensive patients : the losartan intervention for endpoint (LIFE) reduction in hypertension study.

Obesity may limit sensitivity of ECG voltage criteria for left ventricular hypertrophy (LVH) because of the attenuating effects of increased body mass on precordial voltages. However, obesity is associated with an increased prevalence of anatomic LVH, making more accurate ECG criteria in obese patients a clinical priority. ECG LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria was used to select patients for the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study. Clinical and ECG data were available in 8417 patients (54% women; mean age, 67+/-7 years); 2519 were overweight and 1573 were obese by gender-specific body mass index criteria. Increased body mass index had significant but directionally opposite effects on ECG LVH by these 2 criteria. Compared with normal-weight patients, obese and overweight patients had lower Sokolow-Lyon voltage and a lower prevalence of ECG LVH by Sokolow-Lyon criteria (10.9% versus 16.2% versus 31.4%; P<0.001). In contrast, obese and overweight patients had higher mean values of the Cornell product and higher prevalences of ECG LVH by this criterion (75.1% versus 69.9% versus 60.7%; P<0. 001). After adjustment for age, gender, race, myocardial infarction, and diastolic and pulse pressure with the use of logistic regression analysis, increased body mass remained highly predictive of the presence of ECG LVH. Compared with normal-weight patients, obese patients had a >2-fold higher risk of ECG LVH by the Cornell product but a 4-fold lower risk of ECG LVH by Sokolow-Lyon voltage; overweight status was associated with intermediate risks, with a 151% greater likelihood of ECG LVH by the Cornell product but only 44% of the risk of LVH by Sokolow-Lyon voltage criteria compared with normal-weight individuals. Thus, Sokolow-Lyon voltage criteria underestimate the prevalence of anatomic LVH in the presence of obesity, whereas Cornell product criteria for ECG LVH appear to provide a more accurate measure of LVH in obese and overweight patients.

Impact of different partition values on prevalences of left ventricular hypertrophy and concentric geometry in a large hypertensive population : the LIFE study.

Left ventricular (LV) hypertrophy and concentric remodeling have been defined by using a variety of indexation methods and partition values (PVs) for LV mass and relative wall thickness (RWT). The effects of these methods on the distribution of LV geometric patterns in hypertensive subjects remain unclear. Echocardiograms were obtained in 941 patients with stage I to III hypertension and LV hypertrophy by ECG. LV mass was calculated by using different methods of indexation for body size and different PVs to identify hypertrophy: LV mass/body surface area (g/m(2)) PV for men/women 116/104, 125/110, or 125/125; LV mass/height (g/m) PV 143/102 or 126/105; and LV mass/height(2.7) (g/m(2.7)) PV 51/51 or 49.2/46.7. RWT was calculated by either 2xend-diastolic posterior wall thickness (PWT)/end-diastolic LV internal dimension (LVID) or end-diastolic interventricular septum dimension+end-diastolic PWT/end-diastolic LVID. LV hypertrophy or remodeling was present in 63% to 86% of subjects, and LV hypertrophy was present in 42% to 77%. By any index, eccentric hypertrophy was the common LV geometric pattern. Use of interventricular septum dimension+PWT/LVID to calculate RWT slightly increased the prevalence of normal geometry and eccentric hypertrophy compared with the use of 2xPWT/LVID. Subjects with LV hypertrophy identified by only LV mass/height(2.7) PV 49.2/46.7 were more obese, whereas those identified by only LV mass/body surface area PV 116/104 were taller and thinner than those in the 2 concordant groups with or without LV hypertrophy by both criteria. By either criterion, there were no significant differences between different LV geometric patterns in clinical cardiovascular disease. Hypertensive patients with LV hypertrophy by ECG have a high prevalence of geometric abnormalities, especially eccentric hypertrophy, irrespective of method of indexation or PV. LV mass indexation by body surface area or height(2.7) identifies lean and obese subjects, respectively. We found no difference in prevalent cardiovascular disease in subjects identified by either criterion, suggesting a similar high risk.

Characteristics of 9194 patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint Reduction in Hypertension.

-Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (<17%) than in the general population, and approximately 7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal, <140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death.

Hemodynamic response, safety, and efficacy of isradipine in the treatment of essential hypertension.

The hemodynamic response achieved by isradipine is balanced; there is a marked decrease in total peripheral resistance with no clinically significant tachycardia or cardiodepressant effect, no fluid retention (natriuretic/diuretic effect) or orthostatic reactions, whereas the blood flow to vital organs is preserved. The blood pressure-lowering effect of isradipine as monotherapy is dose dependent and has shown a greater efficacy than propranolol, hydrochlorothiazide, and prazosin, without an increase in adverse effects. Combination therapy with a beta-blocker is also safe and offers a useful additional reduction in blood pressure. Indeed, the side effects are no more frequent than with placebo (in doses below 10 mg daily); they are also dose dependent and appear to diminish with time. Isradipine's antiatherogenic effects and cardiac protection potential require further evaluation in clinical studies, but add an interesting aspect to the drug. Against this background, isradipine appears to be a useful addition to our therapeutic arsenal and has the potential to become the drug of choice in the treatment of hypertension.

Additive effect of isradipine in combination with captopril in hypertensive patients.

The effects of combined treatment with the calcium antagonist isradipine and the angiotensin-converting enzyme inhibitor captopril were investigated in a randomized, placebo-controlled parallel-group trial comprising 28 patients with essential hypertension. The average age was 50 years (range, 31 to 65 years). After all patients were given captopril 50 mg twice daily plus placebo for four weeks, they were randomly assigned into groups receiving in addition either placebo or isradipine 1.25 mg twice daily in increasing doses at four-week intervals. During Weeks 20 to 24, the captopril plus placebo group was given hydrochlorothiazide 12.5 mg per day. Blood pressure was measured in the morning, 12 hours after tablet intake. Supine blood pressure was reduced in the captopril plus isradipine group by -8/-6, -14/-9, -16/-8, and -11/-7 mm Hg compared with the placebo group. Changes in diastolic blood pressure were statistically significant at Week 8, whereas changes in systolic blood pressure were statistically significant at Weeks 12, 16, and 20. With the addition of hydrochlorothiazide (Weeks 20 to 24), only supine systolic blood pressure was significantly reduced. One patient was withdrawn from the trial due to a rash. The results indicate that combined treatment with a calcium antagonist and an angiotensin-converting enzyme inhibitor is effective in lowering blood pressure and that the combination is well tolerated during long-term therapy. The combination of captopril and isradipine was more effective than captopril given with a low dose of hydrochlorothiazide.

Improved blood pressure control with isradipine in hypertensive patients treated with pindolol.

Isradipine is a new calcium antagonist of the dihydropyridine type with marked vasodilator activity and minimal negative inotropic effects. It is a potent antihypertensive drug when given as monotherapy. This was a randomized double-blind crossover study of 16 weeks' duration, including 80 hypertensive patients with diastolic blood pressures of at least 95 mm Hg who had shown clinically relevant antihypertensive responses, but no normalization of blood pressure during pindolol 10 to 15 mg once daily as monotherapy. Either isradipine or placebo was added to the beta-blocker at doses of either 2.5 mg or 5 mg twice daily, which was doubled after four weeks if the diastolic blood pressure remained more than 90 mm Hg. The addition of isradipine (in either dose regimen) caused a pronounced reduction of blood pressure with no changes in heart rate. Five patients were withdrawn from the study because of adverse events while receiving isradipine compared with three taking placebo. A further three patients withdrew from the study because of adverse events (one patient) or lack of efficacy (two patients) during placebo treatment. These results indicate that isradipine is an effective and well-tolerated adjunct to beta-blockers in hypertensive patients.