Detection of left ventricular hypertrophy by different electrocardiographic criteria in clinical practice. Findings from the Sara study.

The objective of this study is to compare the validity of different product duration-based electrocardiographic criteria with the classical voltage criteria and to estimate the prevalence of left ventricular hypertrophy (LVH) for each criterion. Electro cardiographic criteria from 248 hypertensive patients attended in daily clinical practice were examined. Cornell and Sokolow-Lyon voltage indexes, Cornell and Sokolow-Lyon products, and Cornell and Sokolow-Lyon areas were determined. The presence of echocardiographic LVH was documented from the patients' clinical records. The proportion of patients with LVH detected by Cornell product was 27.3% vs. 12.9% by Cornell voltage, and 23.6% by Sokolow-Lyon product vs. 12.0% by Sokolow voltage. Both were p < 0.05. When QRS area criteria were applied, ECG-LVH was present in 32.7% (Cornell area) and 29.5% (Sokolow area) of the patients, respectively. When the composite of several criteria was applied, the detection of LVH with the combination of the Cornell product and the Sokolow-Lyon voltage index increased to 33% and with the combination of Cornell and Sokolow-Lyon products reached 39.3%. Globally, the patients diagnosed by voltage criteria were older, had higher systolic blood pressure (SBP) and a longer history of hypertension when compared to subjects diagnosed by product or area-based criteria. The Cornell and Sokolow-Lyon product and the QRS area-based criteria improve the detection of ECG-LVH in the hypertensive population. The composite of different criteria may be a useful strategy to further increase the diagnostic ability of ECG. The combinations of the Cornell product with the Sokolow voltage or with the Sokolow product appear to be the most efficient options.

Gender differences in the diagnosis and treatment of left ventricular hypertrophy detected by different electrocardiographic criteria. Findings from the SARA study.

This study examines the influence of gender on the detection of left ventricular hypertrophy (LVH) by different electrocardiographic (ECG) criteria and the potential changes induced by antihypertensive therapy from the SARA study ("eStudio del trAtamiento con candesaRtan en pacientes con hipertensión Arterial según criterios electrocardiográficos") database. The SARA study was aimed to determine the effect of a 12-month candesartan-based regimen on ECG-LVH. Overall, 264 patients were included. Cornell voltage index (CorV), Cornell product (CorP), Sokolow-Lyon voltage index (SokV), and Sokolow-Lyon product (SokP) were calculated. At baseline, 39.3% of women and 15.4% of men exhibited ECG-LVH by CorP criteria, and 18.2% of women and 30.6% of men had LVH by SokP. When voltage criteria were applied, LVH was detected in 20.5% of women and 5.9% of men by CorV, and in 10.7% and 13.4%, respectively, by SokV. At the end of the study, the proportion of patients with ECG-LVH by CorP was 28.7% in women (P < 0.001) and 14.4% in men (P = not significant [n.s.]), and in 21.2% (P = n.s.) and 22.1% (P = 0.01) by SokP. Left ventricular hypertrophy by CorV were present in 17.9% of women and 9.0% of men (both P = 0.001), and in 10.6% and 13.3%, respectively by SokV (both P = n.s.). In ECG-LVH hypertensive patients, candesartan was an efficacious drug to regress LVH in the clinical practice setting. The voltage-duration product criteria suggestively detected ECG-LVH and its respective changes better than voltage criteria. Although in daily clinical practice the use of both product criteria seemed clearly preferable to voltage for assessment of ECG-LVH, the CorP appeared to be markedly more useful in women and SokP in men.

Electrocardiographic left ventricular hypertrophy regression induced by an angiotensin receptor blocker-based regimen in hypertensive patients with diabetes: data from the SARA study.

INTRODUCTION: This study examined the influence of diabetes on left ventricular hypertrophy (LVH) detected by different electrocardiographic (ECG) criteria and its changes induced by a 12-month candesartan-based regimen. METHODS: The patients were treated for a 12-month period with a candesartan-based regimen (8/16 mg + hydrochlorothiazide12.5 mg + additional drugs to target blood pressure < 140/90 mmHg [< 130/80 in diabetics]). Cornell voltage index (CorV), Cornell product (CorP), Sokolow-Lyon voltage index (SokV), and Sokolow-Lyon product (SokP) were calculated. In total 276 patients were included, 51 with diabetes. RESULTS: At study end, blood pressure was reduced 19.0+/-9.2/7.3+/-3.4 mmHg in diabetic patients and 18.8+/-9.1/8.0+/-3.2 mmHg in non-diabetic subjects (both p<0.01 vs. baseline; p=0.85 between groups).At baseline, 37.5% of diabetic and 26.4% of non-diabetic patients fulfilled criteria of ECG-LVH by CorP (p=0.02), 25.7% and 23.2%, respectively, by SokP (p=0.18), 11.8% and 13.7% by CorV (p=0.16), and 14.3% and 11.6% by SokV (p=0.10).At study end, the prevalence of ECG-LVH was reduced to 25.1% (relative risk reduction [RRR] 33.3%, p=0.001) and 18.2% (RRR 29.2%, p=0.001) by CorP and SokP, in diabetic patients, respectively. In non-diabetic patients, only the CorP criterion showed a significant decrease (RRR 18.9%, p=0.01). No significant changes were observed by other criteria.The RRR of ECG-LVH with treatment was significantly higher in diabetics according to CorP and SokP criteria. CONCLUSIONS: The prevalence of ECG-LVH detected by CorP was higher in diabetics. Diabetics achieved higher reductions in ECG-LVH prevalence than non-diabetics with a candesartan-based regimen.

Electrocardiographic left ventricular hypertrophy regression induced by an angiotensin receptor blocker-based regimen in hypertensive patients with the metabolic syndrome: data from the SARA Study.

The authors assessed the effect of an angiotensin receptor blocker (candesartan)-based regimen on electrocardiographic left ventricular hypertrophy (ECG-LVH) in 276 patients with hypertension, including 141 with the metabolic syndrome (MS). Baseline blood pressure (BP) and ECG-LVH parameters did not differ in patients with and without MS. At the study's end, BP had decreased similarly in both groups. At baseline, 26.1% of patients with MS and 24.7% without MS exhibited ECG-LVH by Cornell product (CorP) criteria (P=NS); 26.8% and 17.2%, respectively, by Sokolow-Lyon product (SokP) (P=.01); 11.4%and 11.8% by Cornell voltage (CorV) (P=NS); and 12.4% and 6.5% by Sokolow-Lyon voltage (SokV) (P=.01). At the study's end, in the MS group, prevalence of ECG-LVH was reduced to 19.5% from 26.1% (P=.001), to 8.5% from 11.4% (P=.01), and to 24.4% from 26.8%(P=.03) by CorP, CorV, and SokP, respectively. In patients without MS, only the CorP criterion showed a significant decrease in ECG-LVH prevalence, declining to 20.5% (P=.01). The relative risk reduction of ECG-LVH was higher in patients with MS according to CorV and SokP criteria (P<.01).

Electrocardiographic left ventricular hypertrophy regression induced by an angiotensin receptor blocker-based regimen in daily clinical practice: the SARA study.

AIM: Clinical trials have proved that angiotensin receptor blockers (ARB) are more effective than other antihypertensive agents in reducing left ventricular hypertrophy (LVH); however, information about the efficacy of ARB on LVH regression in daily medical practice is scarce. The aim of the SARA study was to investigate the effect of an ARB on electrocardiographic LVH (ECG-LVH) in a hypertensive outpatient population attending clinical practice. METHODS: From 276 recruited patients with mild-to-moderate essential hypertension (245 uncontrolled, 31 newly diagnosed), 264 (age: 62.9+/-11.6 years; 51.2% women) completed the study and were valid for the analysis. The patients were treated for a 12-month period with a candesartan-based regimen [(8/16 mg+hydrochlorothiazide 12.5 mg+additional drugs to target BP<140/90 mmHg (<130/80 in diabetics)]. ECG changes were measured at a core laboratory and Cornell product (CorP), Sokolow-Lyon product (SokP) and QRS duration (QRSd) criteria were determined. RESULTS: At baseline, 27.4% of patients fulfilled the criteria of LVH by CorP. The proportion of patients with ECG-LVH by CorP criteria decreased to 21.1% at the end of the study, relative risk reduction (RRR) was 22.9%, P<0.001. When using SokP the percentage of ECG-LVH reduced from 24.1 to 21.7% (RRR 9.6%, P=0.1). Quantitatively, CorP was reduced by 84.4 mmxms [95% confidence interval (CI): -8.14, -160.66; P=0.03]; a greater reduction was detected in obese patients (P<0.05), diabetics (P<0.07) and patients with baseline ECG-LVH (P<0.05). In the multivariate analysis, female gender, baseline systolic blood pressure, baseline CorP and QRSd values were the main predictive factors for ECG-LVH regression. CONCLUSION: The SARA study demonstrates that a candesartan-based regimen reduces ECG-LVH in the hypertensive population attending daily in clinical practice.

Role of endothelin-1 and thromboxane A2 in renal vasoconstriction induced by angiotensin II in diabetes and hypertension.

BACKGROUND: Interactions among angiotensin II (Ang II), endothelin-1 (ET-1) and thromboxane A2 (TXA2) may play an important role in the regulation of renal function. The present study investigated the participation of TXA2 and ET-1 in the increase in renal vascular resistances (RVR) induced by Ang II, as well as the consequences of diabetes, hypertension, and the combination of both on this response. METHODS: Isolated kidneys from male normoglycemic or streptozotocin-induced diabetic Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used. The increase in perfusion pressure (PP) produced by Ang II was studied in the absence or presence of the TXA2 receptor antagonist, ifetroban, or the ETA/ETB receptor antagonist, PD145065. RESULTS: Systolic arterial pressure (SAP) was higher in SHR than in WKY, but diabetic rats (D) from each strain showed lower SAP values than their respective non-diabetic rats. Basal renal PP was higher in WKY and SHR than in WKY-D and SHR-D. Increases in renal PP produced by Ang II were comparable in the kidneys from all groups. Either ifetroban or PD145065 reduced the maximal Ang II response in all animals. The maximal inhibitory effect of ifetroban was higher (P<0.05) in WKY than in the other groups. However, the maximal inhibitory effect of PD145065 was lower in SHR than in the other groups. CONCLUSION: This study supports a role for ET-1 and TXA2 as mediators of the increase in renal vascular resistance produced by Ang II. These results indicate that the participation of ET-1 in the renal vasoconstriction produced by Ang II was reduced under hypertensive conditions, and that of TXA2 was reduced by both diabetes and hypertension.

N-acetylcysteine potentiates the antihypertensive effect of ACE inhibitors in hypertensive patients.

Sulfhydryl group donors, such as N-acetylcysteine (NAC), may enhance the antihypertensive effect of some drugs through a nitric oxide (NO) mechanism. It has been observed that the hypotensive effect of angiotensin-converting enzyme inhibitors (ACEIs) is, at least partially, mediated by NO. We performed a within patient crossover study with the aim to investigate the potential effect of NAC on the ACEI antihypertensive action, via an NO-dependent mechanism. We studied 18 smoker (> 10 years of habit and > 10 cigarettes daily) hypertensive patients (15 males and three females, aged 69 +/- 5 years) on ACEI therapy (11 captopril and seven enalapril). Patients were randomly allocated to two treatment arms. In one arm, the patients (n = 10) initially received the addition of NAC (600 mg t.i.d.) to the ACEI regimen. In the other group (n = 8), the patients remained only on ACEI. After 21 days, the therapeutic patterns were crossed. The first group received only ACEI, and the second group received ACEI and NAC and completed other 21-day treatment period. We evaluate the effect of NAC on each patient by ambulatory blood pressure monitoring (ABPM), performed at the end of each therapeutic regimen. A significant decrease in systolic and diastolic 24-h blood pressure (24 hBP) and daytime BP (dtBP) was achieved with the combination of ACEI and NAC (ACEI + NAC) when compared to the period with only ACEI: 24 hBP = 146.1 +/- 4.2 vs 137 +/- 3.1 (p < 0.05) and 89.2 +/- 2.8 vs 83.5 +/- 3.7mmHg (p = 0.01). DtBP: 149.7 +/- 5.6 vs 141 +/- 3.7 and 92.1 +/- 4 vs 86 +/- 3.2 (both, p < 0.05). No significant difference was observed in night-time BP (ntBP). The NAC effect was not statistically different for the two ACEIs. In conclusion, the addition of NAC to an ACEI potentiates its antihypertensive effect during 24hBP and dtBP in smoker hypertensives. This effect may be mediated by an NO-dependent mechanism, probably through the protective effect of NAC on NO oxidation.

Antihypertensive efficacy and tolerability of lercanidipine in daily clinical practice. The ELYPSE Study. Eficacia de Lercanidipino y su Perfil de Seguridad.

AIM: Lercanidipine, a long-acting dihydropyridine with a good antihypertensive efficacy and tolerability in clinical use. With the aim to determine the efficacy and tolerability of this drug in usual clinical practice we performed the ELYPSE trial. METHODS: Grade 1 or 2 essential hypertensive patients in whom their physicians considered to prescribe a dihydropyridine were conferred to Lercanidipine 10 mg once daily with a 3-month follow-up; 9059 patients were included (age: 63 +/- 11 years; 58% women, 60% over 60 years, 56% grade 2 hypertensives and 69% previously treated with other antihypertensive drugs). A subgroup of 1267 patients (14%) who were included in the study had experienced adverse reactions with other drugs. Electronic case-report forms and a central database (Internet) were used in this trial. RESULTS: At baseline, blood pressure (BP) was 160.1 +/- 10.2/95.6 +/- 6.6 mmHg; and heart rate (HR) 77.3 +/- 9.3 beats/min. Significant reductions in both systolic and diastolic BP were attained at 1 month with slight additional decreases 2 months later. At 3 months, BP was 141.4 +/- 11.3/ 83.1 +/- 6.9 mmHg, and HR 75.2 +/- 8.2 beats/min (p < 0.001 versus baseline). At the study end. 64% of the patients achieved a diastolic BP < 90 mmHg, BP control (< 140/90 mmHg) was attained in 32%. In the subgroup of diabetics (n = 1269) an adequate BP control (< 130/85) was attained in only 16.4%. The overall incidence of adverse events was 6.5%, of which the most frequent were headache (2.9%), ankle oedema (1.2%), flushing (1.1%) and palpitations (0.6%). Withdrawal rate was < 1%. The efficacy and tolerability in the subgroup of patients included in the study due to adverse events with other drugs were similar to the whole study group. CONCLUSION: In this study Lercanidipine has shown a good efficacy and tolerability in daily clinical practice. These findings are concordant with those reported in randomized controlled trials.

Renal dysfunction after chronic blockade of nitric oxide synthesis.

The effects of the chronic inhibition of nitric oxide (NO) on renal hemodynamics and tubular function were studied in rats treated for 8 weeks with the NO synthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg/day). In addition, the effect of L-NAME administration on vasoactive systems (renin-angiotensin system, aldosterone, catecholamines, endothelin, and thromboxane A(2)) was evaluated. Chronic inhibition of NO significantly elevated blood pressure, reduced glomerular filtration rate and renal blood flow, blunted the pressure-diuresis-natriuresis response, and increased protein urine excretion. All these changes were associated with blunted nitrite production in response to acetylcholine in glomeruli. No changes were observed in the plasma levels of either renin activity, aldosterone, or endothelin in L-NAME-treated rats. Similarly, no differences were observed in the urinary excretion of thromboxane B(2) between both group of animals. By contrast, plasma concentrations of both epinephrine and norepinephrine were elevated in rats treated with L-NAME. In summary, the results show that chronic blockade of NO produced not only alterations in renal function, but also renal damage, suggesting an important renoprotective role of NO. An activation of sympathoadrenal system could participate in these renal alterations.