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Background & Aims: Increased left ventricular mass (LVM) is often present in metabolic syndrome (MS), also in the setting of well-controlled blood pressure (BP). Aim of the present study was to evaluate the efficacy of a nutraceutical combination of berberine, red yeast rice extract and policosanol (Armolipid Plus™, AP) in reducing LVM in patients with MS and left ventricular hypertrophy (LVH)., Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 158 patients with MS (IDF criteria) and LVH (LVM > 48 g/m 2.7 in men and > 44 g/m 2.7 in women), were randomized 1:1 to receive AP or placebo for 24 weeks. Reduction of LVM, regression of LVH, and changes in lipids were analysed., Results: One-hundred-and-forty-five patients (AP n = 74, placebo n = 71) completed the study. A significant percentage reduction in LVM was observed in AP group vs baseline (-2.7%, p < 0.0001), and compared to placebo (-4.1%, p < 0.0001), and remained significant after adjustment for age, sex, baseline systolic BP and BMI and their changes during the study period. The proportion of subjects showing LVM reduction was higher in AP group than in the placebo group (57% vs 28%, adjusted p = 0.007). Treatment with AP was associated with improvement of lipid profile., Conclusions: 24-week of treatment with AP is associated with a significant reduction in LVM in subjects with MS and LVH, in addition to favourable effects on lipid profile, and could represent an effective strategy aiming at reducing the associated cardiovascular risk. The trial was registered at clinicaltrials.gov with ID NCT02295176., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Method: We investigated whether aortic characteristic impedance (Zc), that is, the ratio between the pulsatile change in pressure and flow in the proximal aorta, is related to left ventricular hypertrophy and geometry independently of blood pressure (BP). A total of 438 never-treated hypertensive individuals (men 62%, age 48 ± 11 years, BP 147/90 ± 16/10  mm Hg) underwent echocardiography and 24 h BP monitoring. Aortic pressure waveform was obtained from radial tonometry with a generalized transfer function (SphygmoCor). Using a validated aortic blood flow model based on higher order Windkessel theory (ARCSolver), aortic Zc, forward (Pf) and backward (Pb) wave amplitudes and their ratio (Pb/Pf = reflection magnitude) were calculated from central waveform., Results: After adjusting for age, BMI, and 24-h SBP, aortic Zc was higher in individuals with left ventricular hypertrophy (0.230 ± 0.09 vs. 0.205 ± 0.07 arbitrary units, P = 0.04 in women; 0.232 ± 0.07 vs. 0.214 ± 0.06 arbitrary units, P < 0.05 in men). Women with left ventricular concentric remodeling had higher adjusted Zc (0.225 ± 0.08 vs. 0.203 ± 0.07 arbitrary units, P = 0.04), whereas men did not differ (0.218 ± 0.07 vs. 0.218 ± 0.07 arbitrary units, P = 0.64). After controlling for age, BMI, 24 h SBP, and other relevant variables, aortic Zc independently predicted left ventricular mass (β = 0.14, P < 0.05) and relative wall thickness (β = 0.21, P < 0.01) in women, and left ventricular mass in men (β = 0.11, P < 0.05), whereas other arterial function parameters had no independent relation with left ventricular mass or geometry., Conclusion: Aortic Zc has a significant association with left ventricular mass and a sex-specific one with left ventricular concentric geometry in hypertension. These effects are independent from, and additional to, those of 24 h SBP.

Background and Aim: Morbid obesity is often accompanied by insulin resistance and increased ectopic fat surrounding the heart. We evaluated the relation of epicardial and pericardial fat with insulin resistance and left ventricular (LV) structure and function., Methods and Results: Epicardial and pericardial fat thicknesses were determined at 2-dimensional echocardiography in 80 morbid obese subjects [age 42 ± 12 years, 31% men, body mass index (BMI) 44.4 ± 7 kg/m(2)]. LV hypertrophy (LV mass ≥51 g/m(2.7)), inappropriately high LV mass for a given cardiac workload (observed vs predicted LV mass >128%), and stress-adjusted LV mid-wall fractional shortening were determined. Pericardial and epicardial fat thicknesses had direct associations with BMI (r = 0.40 and 0.45, both p < 0.01) and waist circumference (r = 0.37 and 0.45, both p < 0.01). Pericardial (partial r = 0.35, p < 0.01), but not epicardial fat thickness (partial r = 0.05, p = n.s.), was correlated with homeostasis model assessment-insulin resistance after adjustment for BMI. Pericardial fat also had a strong negative correlation with mid-wall fractional shortening (p = 0.01) and a positive one with inappropriately high LV mass (p < 0.01), while no such relation was found for epicardial fat (both p = n.s.). Independently of age, male sex, BMI, and anti-hypertensive treatment, pericardial fat thickness had an independent positive association with inappropriately high LV mass (β = 0.29, p = 0.02), and a negative one with stress-adjusted mid-wall fractional shortening (β = -0.26, p = 0.04)., Conclusions: Pericardial fat thickness is associated with insulin resistance, inappropriately high LV mass, and LV systolic dysfunction in obese individuals. Findings from this study confirm the existence of a connection between insulin resistance, cardiac ectopic fat deposition and cardiac dysfunction in morbid obesity., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background and Aim: Twenty-four-hour blood pressure (BP) variability, by ambulatory BP monitoring (ABPM), has been related to left ventricular hypertrophy, independent of mean BP values. We tested the hypothesis that short-term BP variability (BPV) is also related to subclinical left ventricular systolic dysfunction., Methods: We assessed 24-h SBP and DBP variabilities, quantified as standard deviation (SD) of daytime (awake) BP values and as weighted SD of 24-h BP (24-h-weighted BPV), in 309 recently (<6 months) diagnosed, prospectively recruited, and untreated hypertensive patients. Patients were included only if with normal (≥55%) left ventricular ejection fraction (LVEF). Left ventricular systolic function was assessed by echocardiography measuring midwall fractional shortening (MFS), circumferential end-systolic stress (cESS), MFS/cESS, peak systolic wall stress, left ventricular fractional shortening (LVFS), and LVEF., Results: At multivariate analysis, awake and 24-h-weighted SBP variabilities (directly, P = 0.038 and P = 0.002, respectively) as well as relative wall thickness (RWT) (inversely, P = 0.001) were significantly related to cESS. Awake and 24-h SBP average values (inversely, P = 0.011 and P = 0.002, respectively), awake and 24-h-weighted SBP variabilities (inversely, P = 0.017 and P = 0.024, respectively), and RWT (directly, P = 0.001) were all significantly related to MFS/cESS. Finally, awake and 24-h average SBP (directly, P = 0.01 for both), awake and 24-h-weighted SBP variability (directly, P = 0.001 and P = 0.032, respectively), and RWT (inversely, P = 0.001) were all significantly and independently related to peak systolic wall stress., Conclusion: In newly diagnosed never-treated hypertensive patients, in the absence of LVEF changes and independent of left ventricular mass index, higher awake, or 24-h-weighted short-term SBP variabilities are associated with early depressed left ventricular systolic function.

ECG remains the first line method for detection of left ventricular hypertrophy (LVH) in patients with hypertension. ECG diagnosis of LVH predicts a several-fold increase in age- and risk factor-adjusted cardiovascular morbidity and mortality in asymptomatic patients with essential hypertension. When compared with traditional ECG methods, Cornell voltage product and multifactorial criteria such as the Perugia criterion allow detection of LVH in a higher proportion of subjects while carrying a high attributable risk for cardiovascular morbidity and mortality. Hence, traditional interpretation of standard ECG maintains an important role for cardiovascular risk stratification in hypertension., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The Working Group on Electrocardiographic Diagnosis of Left Ventricular Hypertrophy, appointed by the Editor of the Journal of Electrocardiology, presents the alternative conceptual model for the ECG diagnosis of left ventricular hypertrophy (LVH). It is stressed that ECG is a record of electrical events, not of mechanical events and/ or anatomical characteristics. Considering the electrical characteristics of pathologically changed myocardium should lead to better understanding and improved clinical usefulness of the ECH in the clinical diagnosis of LVH., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The interpretation of serial electrocardiographic (ECG) changes in hypertensive subjects is uncertain. We tested the hypothesis that serial changes in repolarization and voltage are independent determinants of outcome., Methods: The Hypertrophy at ECG And its Regression during Treatment (HEART) Survey was a prospective observational study performed at 61 centers. We studied 711 subjects with hypertension and ECG left-ventricular hypertrophy (LVH) at entry. Tracings from 496 subjects at entry and one or more visits during follow-up were available for central reading., Results: The prevalence of ECG LVH progressively decreased by 49.6% at 3 years. The crude rate of a prespecified primary composite end point of cardiovascular events was 4.17 per 100 subjects per year (95% confidence interval [CI], 3.27 to 5.33). We used Cox regression models of ECG LVH indexes as time-varying covariates at baseline and at follow-up. Time-varying LVH, defined as an absence of ST-T alterations ("strain"), was associated with a lower event rate hazard ratio (HR), 0.47; 95% CI, 0.28 to 0.78; P = .0035), whereas the LVH changes defined in terms of ECG voltages did not achieve significance (HR, 0.91; 95% CI, 0.74 to 1.13; P = .39). The crude event rate in subjects with versus without in-treatment ST-T alterations on the last available ECG before the event or before censoring was 8.38 versus 3.17 per 100 subjects per year (P < .0001)., Conclusions: In this study of subjects with hypertension and ECG LVH at entry, serial changes in repolarization significantly predicted the prognosis, independent of voltage change (which was not significantly predictive in this study). The persistence or new development of ST-T alterations identifies subjects at very high risk of cardiovascular events.

Growing evidence associates blood pressure (BP) variability with cardiovascular events in hypertensive patients. Here we tested the existence of a relationship between awake BP variability and target-organ damage in subjects referred for suspected hypertension. Systolic and diastolic BP variability were assessed as the standard deviation of the mean out of 24-hour, awake and asleep BP recordings in 180 untreated subjects, referred for suspected hypertension. Measurements were done at 15-minute intervals during daytime and 30-minute intervals during nighttime. Left ventricular mass index (by echo), intima-media thickness (by carotid ultrasonography), and microalbuminuria were assessed as indices of cardiac, vascular and renal damage, respectively. Intima-media thickness and left ventricular mass index progressively increased across tertiles of awake systolic BP variability (P for trend=0.001 and 0.003, respectively). Conversely, microalbuminuria was similar in the 3 tertiles (P=NS). Multivariable analysis identified age (P=0.0001), awake systolic BP (P=0.001), awake systolic BP variability (P=0.015) and diastolic BP load (P=0.01) as independent predictors of intima-media thickness; age (P=0.0001), male sex (P=0.012), awake systolic (P=0.0001) and diastolic BP (P=0.035), and awake systolic BP variability (P=0.028) as independent predictors of left ventricular mass index; awake systolic BP variability (P=0.01) and diastolic BP load (P=0.01) as independent predictors of microalbuminuria. Therefore, awake systolic BP variability by non-invasive ambulatory BP monitoring correlates with sub-clinical target-organ damage, independent of mean BP levels. Such relationship, found in subjects referred for recently suspected hypertension, likely appears early in the natural history of hypertension.

Objective: Although electrocardiography (ECG) is recommended in all subjects with hypertension, no information is available on the influence exerted by random changes in the placement of electrodes on the day-to-day variability of ECG criteria for diagnosis of left ventricular hypertrophy (LVH)., Methods: In a multicentre, randomized study, two standard 12-lead ECG were recorded, 24 h apart, from 276 consecutive hypertensive patients (mean age 65 +/- 12 years, 49.6% men). Overall, 142 patients were randomized to ECG with the position of electrodes marked on the skin using a dermographic pen and 134 to traditional ECG without marking the position of electrodes. Day-to-day variability of ECG criteria for LVH was compared between the two groups., Results: Coefficients of variation (SD of the difference between paired voltage measurements divided by the mean value) varied consistently among subjects randomized to ECG without dermographic pen, ranging from 30% (R wave in lead I) to 81% (R wave in lead V5). Dermographic pen led to a lesser variability of ECG voltages with consequent reduction in the coefficients of variation, which ranged from 26% (R-wave amplitude in lead I) to 43% (R-wave amplitude in lead V5). The proportion of subjects who changed classification status for LVH ('reclassification rate') from the first to the second ECG session (LVH present in session 1 and absent in session 2, or vice versa) decreased for effect of dermographic pen from 11 to 4% (P = 0.040) with the Cornell voltage, from 19 to 11% (P = 0.029) with the Sokolow-Lyon voltage, and from 18 to 7% with the Romhilt-Estes criterion (P = 0.018), but not with other criteria. In particular, the typical strain and the Cornell strain were associated with the lowest reclassification rates regardless of dermographic pen., Conclusions: Random changes in the position of ECG electrodes strongly impair the day-to-day reproducibility of Cornell voltage, Sokolow-Lyon and Romhilt-Estes criteria for LVH. The typical strain and Cornell strain criteria showed a lesser spontaneous day-to-day variability.

Metabolic syndrome (MS) is increasingly recognized as an important cardiovascular risk factor in hypertension, but its influence on left ventricular (LV) mass and function in the 2 genders has not been specifically addressed. Among 618 nondiabetic, untreated hypertensive subjects, echocardiographically detected LV mass was significantly greater in subjects with MS. A significant interaction was observed between sex and the MS (P<0.003 for the multiplicative interaction term). Compared with women without the MS, those with the syndrome had a 24% greater LV mass (49.5+/-12 versus 40.0+/-10 g x m(-2.7); P<0.001), whereas the difference was only 9% in men (50.3+/-12 versus 46.1+/-10 g x m(-2.7); P=0.003). A greater prevalence of LV hypertrophy was found in women (37% versus 14%; P<0.001) but not in men (39% versus 29%; P=0.09) with the MS. After adjustment for the effect of age, body mass index, 24-hour systolic blood pressure, and several confounders, the MS was independently associated with a greater LV mass index in women (regression coefficient, 4.80; P<0.001) but not in men. Women with the MS also had a greater LV relative wall thickness (0.42+/-0.07 versus 0.39+/-0.07; P=0.004) and a depressed afterload-corrected midwall fractional shortening (94.0+/-12% versus 101.0+/-13%; P<0.001) than women without the syndrome, whereas no differences emerged in men. We conclude that, in untreated hypertension, MS has a different impact on LV hypertrophy and function in men and women. The effect of MS is more pronounced in women and is partly independent from the effect of several hemodynamic and nonhemodynamic determinants of LV mass.

Background: Few data are available on the long-term effects of weight loss on 24-h blood pressure (BP) and left ventricular mass in overweight hypertensive patients., Methods: A total of 181 never-treated overweight hypertensive subjects (body mass index, 25 to 39 kg/m(2), office BP 145/94 +/- 12/7 mm Hg) had 24-h BP monitoring and echocardiography twice, at baseline and after 3.8 +/- 2 years (minimum 1 year). None of the subjects received antihypertensive drugs during the follow-up. Main outcome measures were changes in 24-h BP and in left ventricular mass., Results: Percent change in body weight had a direct relationship with 24-h BP changes (r = 0.35 and 0.31 for systolic and diastolic BP, respectively; both P <.001). The associations with office BP changes (r = 0.13, P =.10 for systolic BP; r = 0.15, P =.06 for diastolic BP) were significantly weaker (both P <.01, z test). The patients who lost weight during follow-up (n = 106) had a significantly lower increase in 24-h BP (+0.6 +/- 9/ +0.2 +/- 6 v +4.9 +/- 9/ +2.7 +/- 7 mm Hg for systolic/diastolic BP, both P <.01) and in left ventricular mass (-3 +/- 30 g v +9 +/- 32 g, P <.02) than the remaining subjects. In a multiple linear regression, a 10% weight loss independently predicted a 4.3/3.8 mm Hg decrease in 24-h systolic/diastolic BP., Conclusions: Long-term weight loss determines a sustained BP reduction during the 24 h and a decrease in left ventricular mass in overweight hypertensive subjects. The relation of weight loss with ambulatory BP changes is closer than that with office BP.

Background: Left ventricular hypertrophy (LVH) detected at electrocardiography (ECG) is a predictor of an increased cardiovascular risk in essential hypertension. However, uncertainty remains concerning the reproducibility of ECG LVH and the prognostic relevance of its regression over time in hypertension. The aim of this study was to determine the prognostic value of baseline ECG LVH and its serial changes in a large cohort of hypertensive patients., Methods: The Hypertrophy at ECG and its Regression during Treatment Survey (HEART Survey) is a prospective observational study conducted in 66 Italian centers. Inclusion criteria are essential hypertension with ECG LVH defined by the Perugia score (Cornell voltage criteria and/or a typical left ventricular "strain" pattern and/or a Romhilt-Estes score > or = 5 points) in subjects aged 45-84 years. The treatment of hypertension and other risk factors accords with current guidelines and is individually tailored. ECG is recorded twice at entry and periodically repeated over a 4-year follow-up period. Expert readers (unaware of the clinical findings) classify ECG. The incidence of major cardiovascular events in relation to baseline ECG and its changes over time are assessed, together with the reproducibility in the two baseline recordings. Overall, 708 patients aged 64 +/- 9 years have been enrolled in centers from northern (27%), central (32%) and southern (41%) Italy. Their baseline characteristics are presented. Follow-up is ongoing., Conclusions: The HEART Survey will examine the prognostic value of baseline ECG LVH and of its regression over time in a wide population of hypertensive patients.

Background: Elevated pulse pressure, an index of increased large artery stiffness, has been associated with increased left ventricular mass. It is unknown whether this relation is independent or mediated by other blood pressure components., Methods and Results: We examined data in 2545 untreated hypertensive subjects (45% women) who underwent echocardiography and 24-h ambulatory blood pressure monitoring. Left ventricular mass increased with all blood pressure components and all associations were closer with ambulatory than with office blood pressure. In a multiple regression analysis, after adjustment for the significant association with age, gender, body weight and duration of hypertension, the proportion of variability of left ventricular mass explained by systolic blood pressure was greater than that explained by other blood pressure components. When different blood pressure components were forced into the same model, the same degree of left ventricular mass variability was accounted for by models including 24-h systolic blood pressure alone, or 24-h mean blood pressure plus 24-h pulse pressure, or 24-h diastolic blood pressure plus 24-h pulse pressure. When 24-h systolic blood pressure and 24-h pulse pressure were forced into the same model, 24-h pulse pressure lost statistical significance., Conclusions: The association between pulse pressure and left ventricular mass is explained by systolic blood pressure, which is the main pressure determinant of left ventricular mass in essential hypertension., (Copyright 2002 The European Society of Cardiology.)

A relation between left ventricular (LV) hypertrophy and depressed midwall systolic function has been described in hypertensive subjects. However, a strong confounding factor in this relation is concentric geometry, which is both a powerful determinant of depressed midwall systolic function and a correlate of LV mass in hypertension. To evaluate the independent contribution of LV mass to depressed systolic function, 1827 patients with never-treated essential hypertension (age 48 +/- 12 years, men 58%) underwent M-mode echocardiography under two-dimensional guidance. Relative wall thickness was the strongest determinant of low midwall fractional shortening (r = -0.63, P < 0.0001). The significant inverse relation observed between LV mass and midwall fractional shortening (r = -0.43, P < 0.0001) persisted after taking into account the effect of relative wall thickness (partial r = -0.27, P < 0.0001). Within each sex-specific quintile of relative wall thickness, prevalence of subnormal afterload-corrected midwall systolic function was greater in subjects with, than in subjects without, LV hypertrophy (P < 0.05 for the first, third, fourth and fifth quintile). In a multiple linear regression analysis, both LV mass (P < 0.0001) and relative wall thickness (P < 0.0001) were independent predictors of a reduced midwall fractional shortening. In conclusion, the inverse association between LV mass and midwall systolic function is partly independent from the effect of relative wall thickness. LV hypertrophy is a determinant of subclinical LV dysfunction independently of the concomitant changes in chamber geometry.

Objective: The proportion of left ventricular (LV) mass variability explained by blood pressure in essential hypertension is small, and several non-haemodynamic determinants of LV mass have been identified or hypothesized. This study examines the possible relation between blood lipids and LV mass in hypertension., Design: Never-treated non-diabetic hypertensive patients., Setting: Hospital hypertension outpatient clinics in Umbria, Italy., Patients: We investigated the association between high-density lipoprotein (HDL)-cholesterol and echocardiographic LV mass in 1306 never-treated subjects with essential hypertension. Subjects with previous cardiovascular events, diabetes and current or previous antihypertensive or lipid-lowering therapy were excluded., Results: HDL-cholesterol showed an inverse association with LV mass (r = -0.30, P < 0.001). No association was found between LV mass and total or low-density lipoprotein cholesterol. With multiple linear regression analysis we tested the independent contribution of several potential determinants of LV mass in women and in men. Average 24 h blood pressure (both pulse and mean), body mass index, height, stroke volume, age (all P < 0.01) and low HDL-cholesterol (P < 0.0001 in women, P < 0.001 in men) were associated with a greater LV mass in both sexes. Triglycerides showed a weak univariate association with LV mass in women (r = 0.11, P < 0.02), which did not hold in a multivariate analysis., Conclusions: Low HDL-cholesterol is an independent predictor of LV mass in untreated hypertensive subjects. Common hormonal and metabolic mechanisms, including insulin resistance, could explain this association, which may contribute to the adverse prognostic significance of low HDL-cholesterol levels.

We followed 1,778 subjects (up to 12 years) with essential hypertension who underwent echocardiography at the time of their initial diagnostic workup. There were 166 major cardiovascular events during follow-up and the prognostic value of the midwall shortening fraction did not remain significant after controlling for left ventricular mass.

The feasibility of echocardiographic determination of left ventricular (LV) mass, as well as the advantages that might be gained in some clinical circumstances and possible indications are examined in the present review, in relation to the recent WHO/ISH. The information obtained with echocardiograms in arterial hypertension is an important contribution to risk stratification on an epidemiological scale. In clinical practice, under the ascertained condition of a good reliability, an echocardiogram should be recommended as part of the initial work up when patients meet criteria for not starting therapy (low or mild risk WHO-ISH) or in all circumstances in which decision-making might be affected by the echocardiographic result. At present, there is not sufficient evidence to extend the indication of echocardiography also to patients for whom antihypertensive management is already necessitated by identification of high or very high risk status.

Background: Left ventricular hypertrophy is an adverse risk marker in essential hypertension and its regression has a favorable effect on prognosis. It is unclear whether blood pressure normalization induced by long-term therapy is able to normalize left ventricular mass completely., Methods: In the setting of a prospective cohort study, 107 consecutive hypertensive patients who achieved blood pressure normalization (clinic blood pressure < 140/90 mmHg on > or = 3 consecutive visits) under long-term (1-10 years, average 2.9) drug treatment were individually matched with 107 healthy normotensive controls by gender, age (+/- 5 years), body mass index (+/- 3 kg/m2), and clinic systolic blood pressure (+/- 5 mmHg) in a case-control design. All subjects underwent 24-hour blood pressure monitoring and M-mode echocardiography., Results: Treated hypertensive patients and normotensive controls did not differ by age, body mass index, clinic blood pressure (128/82 vs 128/81 mmHg), and 24-hour blood pressure (120/77 vs 120/76 mmHg). Left ventricular mass and relative wall thickness were greater in the hypertensive than in the normotensive group (97 +/- 24 vs 86 +/- 17 g/m2 and 0.40 +/- 0.08 vs 0.37 +/- 0.08, both p < 0.001)., Conclusions: Left ventricular mass is greater in well-controlled hypertensive patients than in normotensive controls matched by age, obesity, gender, and clinic and 24-hour blood pressure. This finding is consistent with the lower than epidemiologically expected reduction in coronary heart disease risk during antihypertensive therapy and might reflect the persistent effect on left ventricular mass of hemodynamic and/or non-hemodynamic factors other than blood pressure in treated patients with essential hypertension.

The impact of hypertension on vascular structure at different arterial sites and the relation of vascular hypertrophy with left ventricular (LV) hypertrophy in the early stages of essential hypertension are unclear. In 96 newly diagnosed, never-treated, uncomplicated hypertensive subjects aged < 55 years (43 +/- 9 years, 68 men, clinic blood pressure 152/99 mm Hg, 24-h blood pressure 135/89 mm Hg), we measured LV mass (M-mode echocardiography) and intima-media thickness (IMT) of the carotid and femoral arteries (high-resolution B-mode ultrasound). The average of 24 carotid and 24 femoral IMT readings (common and internal carotid or common and superficial femoral, right and left side, far and near wall, three sampling points per segment) was analyzed. Carotid and femoral IMT were strongly related to each other (r = 0.77). Subjects with LV hypertrophy (n = 33) had a greater IMT at the carotid (0.84 +/- 0.2 v 0.71 +/- 0.2 mm, P < .0001) and femoral (0.77 +/- 0.1 v 0.64 +/- 0.1 mm, P < .0001) level. Carotid IMT showed a positive correlation with LV mass (r = 0.46) and age (r = 0.38), and an inverse one with high-density lipoprotein (HDL) cholesterol (r = -0.26). Femoral IMT was associated positively to LV mass (r = 0.50), age (r = 0.33) and triglycerides (r = 0.29), and inversely to HDL-cholesterol (r = -0.33). The association between IMT (both carotid and femoral) and LV mass held after controlling for age and other confounders in a multiple regression analysis. In summary, in the early stages of hypertension arterial wall thickening appears to be a diffuse process, which occurs in parallel at the carotid and femoral level and shows a positive association with LV hypertrophy.

The detection of left ventricular (LV) hypertrophy on echocardiography is a powerful risk indicator in essential hypertension. However, the prognostic impact of LV mass values within the "normal" range and the shape of the relation between LV mass and prognosis remain unclear. Thus, 1925 white subjects with uncomplicated essential hypertension underwent off-therapy 24-hour blood pressure monitoring and M-mode echocardiography. During 4. 0+/-2 years of follow-up, there were 181 major cardiovascular events (2.4/100 patient-years) and 49 deaths from all causes. In the 5 gender-specific quintiles of LV mass distribution (partition values: 92, 105, 120, and 138 g/m(2) in men and 79, 91, 102, and 116 g/m(2) in women), cardiovascular event rates were 0.8, 1.7, 2.2, 2.9, and 4. 3 per 100 patient-years. After adjustment for several risk factors, including 24-hour ambulatory blood pressure, the relative risk (RR) of developing a cardiovascular event increased progressively from the first quintile (RR 1) to the second (RR 1.6, 95% CI 0.8 to 3.1), third (RR 1.9, 95% CI 1.01 to 4.0), fourth (RR 3.0, 95% CI 1.5 to 5. 8), and fifth (RR 3.5, 95% CI 1.8 to 6.8) quintile. For all-cause death, the RR in the fifth quintile compared with the first quintile was 4.3 (95% CI 1.2 to 13.4). In conclusion, the powerful relation between LV mass and risk of cardiovascular disease in subjects with uncomplicated essential hypertension is continuous over a wide range of LV mass values, even below the current "upper normal" limits. The relation remains significant after control for traditional risk factors, including ambulatory blood pressure.

Electrocardiography (ECG) has a lower sensitivity for the diagnosis of left ventricular (LV) hypertrophy in smokers than in non-smokers, but the explanation for this finding is not known. In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, all subjects smoking > or = 15 cigarettes/day (n = 121, 89 men, age 48 +/- 11 years) were selected from 1443 untreated hypertensive subjects undergoing ECG and M-mode echocardiography, and matched with 484 hypertensive non-smokers by gender (same sex), age (+/- 5 years), and systolic and diastolic blood pressure (both +/- 5 mmHg) in a case-to-control design with a 1:4 matching ratio. Smokers and non-smokers did not differ by age, gender, body mass index, and blood pressure. The voltage of SV1 + RV5 or V6 and RI (p < 0.05), but not of SV3 + RaVL, was lower in smokers. Sensitivity of ECG was lower in smokers when using peripheral or left precordial voltage criteria (e.g. 11 vs 26% for Sokolow-Lyon voltage). When using definitions based on different criteria (voltage of S wave in V3, LV axis, LV strain), sensitivity was not dissimilar in smokers and non-smokers (e.g. 19 vs 18% for Romhilt-Estes score, 40 vs 34% for Perugia criterion). Thus, in hypertensive smokers, sensitivity of ECG is lower than in non-smokers when using peripheral or left precordial voltage criteria, probably due to increased chest size in smokers resulting from increased lung compliance. For LV hypertrophy detection, Sokolow-Lyon voltage should be avoided in hypertensive smokers and replaced by other criteria (Cornell voltage, Romhilt-Estes score, Perugia criterion), which are not influenced by cigarette smoking.

Objectives: We tested the prognostic value of a new electrocardiographic (ECG) method (Perugia score) for diagnosis of left ventricular hypertrophy (LVH) in essential hypertension and compared it with five standard methods (Cornell voltage, Framingham criterion, Romhilt-Estes point score, left ventricular strain, Sokolow-Lyon voltage)., Background: Several standard ECG methods for assessment of LVH are used in the clinical setting, but a comparative prognostic assessment is lacking., Methods: A total of 1,717 white hypertensive subjects (mean age 52 years; 51% men) were prospectively followed up for up to 10 years (mean 3.3)., Results: At entry, the prevalence of LVH was 17.8% (Perugia score), 9.1% (Cornell), 3.9% (Framingham), 5.2% (Romhilt-Estes), 6.4% (strain) and 13.1% (Sokolow-Lyon). During follow-up there were 159 major cardiovascular morbid events (33 fatal). The event rate was higher in the subjects with than in those without LVH (all p < 0.001) according to all methods except the Sokolow-Lyon method. By multivariate analysis, an independent association between LVH and cardiovascular disease risk was maintained by the Perugia score (hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.5 to 2.8) and the Framingham (HR 1.91, 95% CI 1.1 to 3.2), Romhilt-Estes (HR 2.63, 95% CI 1.7 to 4.1) and strain methods (HR 2.11, 95% CI 1.4 to 3.2). The Perugia score showed the highest population-attributable risk for cardiovascular events, accounting for 15.6% of all cases, whereas the Framingham, Romhilt-Estes and strain methods accounted for 3.0%, 7.4% and 6.8% of all events, respectively. LVH diagnosed by the Perugia score was also associated with an increased risk of cardiovascular mortality (HR 4.21, 95% CI 2.1 to 8.7), with a population-attributable risk of 37.0%., Conclusions: The Perugia score carried the highest population-attributable risk for cardiovascular morbidity and mortality compared with classic methods for detection of LVH. Traditional interpretation of standard electrocardiography maintains an important role for cardiovascular risk stratification in essential hypertension.

Background: Increased left ventricular (LV) mass predicts an adverse outcome in patients with essential hypertension. The purpose of this study was to determine the relation between changes in LV mass during antihypertensive treatment and subsequent prognosis., Methods and Results: Procedures including echocardiography and 24-hour ambulatory blood pressure (BP) monitoring were performed in 430 patients with essential hypertension before therapy and after 1217 patient-years. Months or years after the follow-up visit, 31 patients suffered a first cardiovascular morbid event. The patients with a decrease in LV mass from the baseline to follow-up visit were compared with those with an increase in LV mass. There were 15 events (1.78 per 100 person-years) in the group with a decrease in LV mass and 16 events (3.03 per 100 person-years) in the group with an increase in LV mass (P=.029). In a Cox model, the lesser cardiovascular risk in the group with a decrease in LV mass (hazard ratio [HR], 0.46; 95% CI, 0.22 to 0.99) remained significant (P=.04) after adjustment for age (HR, 1.06; 95% CI, 1.03 to 1.10; P=.0008) and baseline LVH at ECG (HR, 3.85; 95% CI, 1.52 to 9.78; P=.012). In that model, baseline LV mass bordered on statistical significance (HR, 1.01; 95% CI, 1.00 to 1.03; P=.06). In the subset with LV mass > 125 g/m2 at the baseline visit (26% of subjects), the event rate was lower among the subjects who achieved regression of LVH than in those who did not (1.58 versus 6.27 events per 100 person-years; P=.002). This difference held in the multivariate analysis (HR, 0.18; 95% CI, 0.05 to 0.68)., Conclusions: In essential hypertension, a reduction in LV mass during treatment is a favorable prognostic marker that predicts a lesser risk for subsequent cardiovascular morbid events. Such an association is independent of baseline LV mass, baseline clinic and ambulatory BP, and degree of BP reduction.

To determine the independent prognostic significance of left ventricular (LV) mass and geometry (concentric vs eccentric pattern) in hypertensive subjects with LV hypertrophy at echocardiography, 274 subjects were followed for up to 8.7 years (mean 3.2). All patients had systemic hypertension and LV mass > or = 125 g/body surface area (BSA) and underwent ambulatory blood pressure (BP) monitoring and echocardiography before treatment. Eccentric and concentric hypertrophy were defined by the ratio between LV posterior wall thickness and LV radius at telediastole <0.45 and > or = 0.45, respectively. Age, sex ratio, body mass index, office BP and serum glucose, cholesterol, and triglycerides did not differ between the groups with eccentric (n=145) and concentric (n=129) hypertrophy. Average 24-hour daytime, and nighttime systolic ambulatory BPs were higher in concentric than in eccentric hypertrophy (all p <0.01). LV mass was slightly greater in concentric than in eccentric hypertrophy (157 vs 149 g/BSA, p <0.05). Endocardial and midwall shortening fraction were lower in concentric than in eccentric hypertrophy (96.5% vs 106.0% of predicted and 71.4% vs 89.7% of predicted, respectively; both p <0.01). The rate of major cardiovascular morbid events was 2.20 and 3.34 per 100 patient-years in eccentric and concentric hypertrophy, respectively (log rank test, p=NS). Age >60 and LV mass above median (145 g/BSA) were significant adverse prognostic predictors, while LV geometry (eccentric vs concentric hypertrophy) and ambulatory BP were not. The event rates per 100 patient-years were 1.38 and 3.98, respectively, in the patients with LV mass below and above median (age-adjusted relative risk 2.70; 95% confidence interval [CI] 1.03 to 6.63; p=0.015). In hypertensive subjects with established LV hypertrophy, LV mass, but not its geometric pattern, provides important prognostic information independent of conventional risk markers including office and ambulatory BP.

The finding of increased left ventricular (LV) mass in hypertensive subjects with blunted nocturnal fall in blood pressure (BP) might be an artifact of matching patients for daytime BP, with resulting higher 24-h BP in nondippers. Therefore, we compared a large number (n = 1048) of hypertensive dippers and nondippers in their LV mass at echocardiography before and after adjustment for 24-h, daytime, and nighttime ambulatory BP. In men, the difference between dippers and nondippers was not significant before and after adjustment for 24-h BP, but after adjustment for nighttime BP LV mass was greater in dippers (more properly "peakers"). In women, LV mass was greater in nondippers than in dippers both before and after adjustment for 24-h BP, while the difference between the two groups disappeared after adjustment for nighttime BP. Thus, for any given level of mean 24-h BP, a flattened diurnal BP profile is associated with a greater LV mass in hypertensive women. Daytime hypertension, either associated or not with a blunted nocturnal fall in BP, may be a sufficient determinant of LV wall thickening in men.

This study was aimed at improving the performance of standard electrocardiographic criteria of left ventricular hypertrophy (LVH) in essential hypertension using echocardiographic left ventricular mass as reference. In 923 white, untreated hypertensive subjects (mean age 51, prevalence of echocardiographic LVH 34%), sensitivity of electrocardiographic criteria of LVH varied between 9% and 33% and specificity was generally > or = 90%. The sum of Sv3 + RaVL (Cornell voltage) showed the closest association with echocardiographic left ventricular mass (r = 0.48, p < 0.001), and its performance was superior to that of Sokolow-Lyon voltage in a receiver-operating characteristic curve analysis. A modified partition value of the Cornell voltage was tested (> 2.4 mV in men and > 2.0 mV in women), that yielded a good combination between sensitivity (26% in men and 19% in women, overall 22%) and specificity (96% in men and 95% in women, overall 95%). When LVH at electrocardiography was defined as the positivity of at least 1 of the following 3 criteria--Sv3 + RaVL > 2.4 mV in men or > 2.0 mV in women, a typical strain pattern, or a Romhilt-Estes point score > or = 5--sensitivity increased to 39% in men and 29% in women (overall 34%) and specificity decreased to 94% in men and 93% in women (overall 93%). Sensitivity of electrocardiography progressively increased from the first to the fourth quartile of left ventricular mass in subjects with echocardiographic LVH.(ABSTRACT TRUNCATED AT 250 WORDS)

Early identification of left ventricular (LV) structural changes may have an impact on the outlook of patients with essential hypertension. Of 669 untreated hypertensive subjects, 496 (74%) with normal LV mass at echocardiography (< 125 g/m2) were grouped according to normal LV geometry (n = 303; 61%), asymmetric LV remodeling due to isolated septal thickening (n = 111; 22%), asymmetric LV remodeling due to isolated posterior wall thickening (n = 5; 1%), or concentric LV remodeling due to septal and posterior wall thickening (n = 77; 16%). Remodeling was defined as twice the thickness of septum or posterior wall divided by the internal diameter at end diastole > 0.45. Twenty-four-hour noninvasive ambulatory blood pressure (BP) monitoring was performed in all subjects. Compared with subjects with normal LV geometry, those with asymmetric LV remodeling due to isolated septal thickening showed increased clinic BP (158/100 vs 153/97 mm Hg, both p < 0.05), mean daytime ambulatory BP (144/95 vs 138/90 mm Hg, both p < 0.01), mean nighttime ambulatory BP (128/80 vs 122/76 mm Hg, both p < 0.01), LV mass (99 vs 89 g/m2, p < 0.001), total peripheral resistance (1,881 vs 1,562 dynes s cm-5, p < 0.01) and known duration of hypertension (5.5 vs 3.6 years, p < 0.01) and decreased stroke index (39 vs 47 ml/m2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)