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The association between raised blood pressure and increased risk of subsequent cognitive decline is well known. Left ventricular hypertrophy (LVH), as a marker of hypertensive target organ damage, may help identify those at risk of cognitive decline. We assessed whether LVH was associated with subsequent cognitive decline or dementia in hypertensive participants aged ≥80 years in the randomized, placebo-controlled Hypertension in the Very Elderly Trial. LVH was assessed using 12-lead electrocardiography (ECG) based on the Cornell Product (CP-LVH), Sokolow-Lyon (SL-LVH), and Cornell Voltage (CV-LVH) criteria. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and annually. A fall in MMSE to <24 or an annual fall of >3 points were defined as cognitive decline and triggered dementia screening (Diagnostic Statistical Manual IV). Death was defined as a competing event. Fine-Gray regression models were used to examine the relationship between baseline LVH and cognitive outcomes. There were 2645 in the analytical sample, including 201 (7.6%) with CP-LVH, 225 (8.5%) SL-LVH and 251 (9.5%) CV-LVH. CP-LVH was associated with increased risk of cognitive decline, subdistribution hazard ratio (sHR)1.3 (95% confidence interval (CI) 1.01-1.67) in multivariate analyses. SL-LVH and CV-LVH were not associated with cognitive decline (sHR1.06 (95% CI 0.82-1.37) and sHR1.13 (95% CI 0.89-1.43), respectively). LVH was not associated with dementia. LVH may be related to subsequent cognitive decline, but evidence was inconsistent depending on ECG criterion and there were no associations with incident dementia. Additional work is needed to understand the relationships between blood pressure, LVH assessment and cognition., (© 2022. The Author(s).)

Previous studies have found that the macrophage migration inhibitor factor is associated with endothelial dysfunction and ventricular remodelling. The aim of this study was to explore the potential relationship between plasma macrophage migration inhibitor factor levels and hypertension and hypertensive left ventricular hypertrophy. A total of 308 participants (including 187 uncomplicated hypertensive patients and 121 healthy controls) were enroled from 2017 to 2019. The association between macrophage migration inhibitor factors and hypertension and hypertensive left ventricular hypertrophy was estimated with univariate and multivariate logistic regression models. Elevated macrophage migration inhibitor factor was associated with the development of hypertension (second tertile: adjusted OR, 2.27, 95% CI, 1.24-4.16, P = 0.008; third tertile: adjusted OR, 5.43, 95% CI, 2.75-10.71, P < 0.001; compared with the first tertile). In addition, we assessed the association between macrophage migration inhibitor factor and left ventricular hypertrophy in hypertensive patients (n = 187). Plasma macrophage migration inhibitor factor was significantly correlated with hypertensive left ventricular mass index (r = 0.580, P < 0.001). In patients with hypertension, an elevated macrophage migration inhibitor factor was significantly associated with hypertensive left ventricular hypertrophy (second tertile: adjusted OR, 3.20, 95% CI, 1.17-8.78, P = 0.024; third tertile: adjusted OR, 24.95, 95% CI, 8.72-71.41, P < 0.001; compared with the first tertile). Receiver operating characteristic analysis indicated that macrophage migration inhibitor factor had reasonable predictive accuracy for the development of hypertensive left ventricular hypertrophy (area under curve 0.84, 95% CI 0.78-0.90, P < 0.001). Our data indicated that elevated macrophage migration inhibitor factor is associated with hypertension and hypertensive left ventricular hypertrophy., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We sought to investigate echocardiography-derived myocardial work in hypertensive patients with different left ventricular (LV) geometric patterns. This cross-sectional study included 211 hypertensive patients (74 with normal LV geometry, 53 with concentric remodeling, 46 with eccentric LV hypertrophy (LVH) and 38 with concentric LVH) who underwent complete two-dimensional echocardiographic examination including two-dimensional speckle-tracking echocardiography. Pressure-strain curve was used to determine parameters of myocardial work. Our findings showed that multidirectional LV strain was lower in patients with eccentric and concentric LVH than in those with normal LV geometry and concentric remodeling. Global myocardial work index and global constructive work were higher in patients with eccentric and concentric LVH than in those with normal LV geometry and concentric remodeling. Global wasted work and global efficacy work were similar between groups with different LV geometry. E/e' and LV mass index were associated with global myocardial work index and global constructive work independently of clinical and echocardiographic parameters. In conclusion, myocardial work was higher in patients with eccentric and concentric LVH than in patients with normal LV geometry and concentric remodeling. Increased blood pressure in patients with concentric LVH in comparison with other LV geometric patterns has significant impact on the final result. LV geometry has significant impact on myocardial work in hypertensive patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Cognitive impairment is common in patients with hypertension. Left ventricular hypertrophy (LVH) is recognised as a marker of hypertension-related organ damage and is a strong predictor of coronary artery disease, heart failure and stroke. There is evidence that LVH is independently associated with cognitive impairment, even after adjustment for the presence of hypertension. We conducted a systematic review that examined cognitive impairment in adults with LVH. Independent searches were performed in Ovid MEDLINE, Ovid psycInfo and PubMed with the terms left ventricular hypertrophy and cognition. Seventy-three studies were identified when both searches were combined. After limiting the search to studies that were: (1) reported in English; (2) conducted in humans; (3) in adults aged 50 years and older; and (4) investigated the relationship between LVH and cognitive performance, nine papers were included in this systematic review. The majority of studies found an association between LVH and cognitive performance. Inspection of results indicated that individuals with LVH exhibited a lower performance in cognitive tests, when compared to individuals without LVH. Memory and executive functions were the cognitive domains that showed a specific vulnerability to the presence of LVH. A possible mechanism for the relationship between LVH and cognition is the presence of cerebral white matter damage. White matter lesions occur frequently in patients with LVH and may contribute to cognitive dysfunction. Together, the results of this review suggest that memory impairment and executive dysfunction are the cognitive domains that showed a particular association with the presence of LVH.

Metabolic syndrome (MS) has been shown to predict cardiovascular events in hypertension. Recently, a new four-group left ventricular (LV) hypertrophy classification based on both LV dilatation and concentricity was proposed. This classification has been shown to provide a more accurate prediction of cardiovascular events, suggesting that the presence of LV dilatation may add prognostic information. We investigated the relationship between MS and the new classification of LV geometry in patients with primary hypertension. A total of 372 untreated hypertensive patients were studied. Four different patterns of LV hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The overall prevalence of MS and LV hypertrophy (LVH) was 29% and 61%, respectively. Patients with MS showed a higher prevalence of LVH (P=0.0281) and dilated LV geometries, namely eccentric dilated and concentric dilated hypertrophy (P=0.0075). Moreover, patients with MS showed higher LV end-diastolic volume (P=0.0005) and prevalence of increased LV end-diastolic volume (P=0.0068). The prevalence of LV chamber dilatation increased progressively with the number of components of MS (P=0.0191). Logistic regression analysis showed that the presence of MS entails a three times higher risk of having LV chamber dilatation even after adjusting for several potential confounding factors. MS is associated with LV dilatation in hypertension. These findings may, in part, explain the unfavourable prognosis observed in patients with MS.

The study aimed to determine the relationship between left ventricular (LV) diastolic function and the heart's spontaneous baroreflex at rest and in response to orthostatic stress during a prospective follow-up of hypertensive patients with LV hypertrophy (LVH+). LV structure and function and baroreflex sensitivity (BRS) during tilt testing were evaluated in 24 LVH+ patients and compared with 25 age-matched healthy controls and 25 hypertensive patients without LVH (LVH-). Clinical status, diastolic function and BRS were then assessed in LVH+ patients during treatment with telmisartan (monotherapy or combined with hydrochlorothiazide and/or amlodipine) at 6- and 18-month follow-ups. LVH+ patients had significantly altered diastolic function indices and decreased BRS as compared with healthy controls and LVH- patients. During the 18-month follow-up, favorable changes in diastolic function were associated with improvement in BRS at rest and during tilting. In multivariate regression models, an index reflecting rate of LV myocardial relaxation (E'sept) where E'sept denotes peak early diastolic velocity at the septal mitral annulus and a surrogate for LV filling pressure (E/E'sept), independently from other clinical and echocardiographic variables related to the low-frequency component of BRS during tilting. In conclusion, the LV diastolic function indices have independent associations with BRS parameters obtained at rest and during orthostatic stress in LVH+ patients receiving long-term pharmacological intervention.

Hypertension is commonly associated with cardiac arrhythmias in patients with and without concomitant cardiovascular disease. Experimental and epidemiological studies have demonstrated potential links between hypertension and atrial and ventricular arrhythmias, although the underlying pathophysiological mechanism remains unclear. Nonetheless, the importance of hypertension as a cause of atrial and ventricular arrhythmias is not well recognized. In particular, the occurrence of left ventricular hypertrophy is a strong predictor for the development of AF, ventricular ectopy and sudden cardiac death. Recent prospective clinical trials reveal that antihypertensive therapy may delay or prevent the occurrence of cardiac arrhythmias and sudden cardiac death in patients with hypertension. Although antihypertensive agents that block the renin-angiotensin-aldosterone system appear to protect against cardiac arrhythmias, this needs to be confirmed by current ongoing clinical trials.

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.

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

Left ventricular hypertrophy (LVH) is prognostically relevant, associated with major cardiovascular risk factors and with atherosclerosis. However, whether LVH is independently associated with impaired coronary flow reserve (CFR) and with endothelial dysfunction is disputed. We assessed the relationship of LV mass and systolic function to CFR and endothelial function in new discovered never treated subjects with essential arterial hypertension, but without coronary artery disease or microalbuminuria. LVH, ejection fraction (EF) and stress-corrected midwall shortening (MWS, a measure of myocardial contractility) were assessed by echocardiography. CFR was assessed by single-photon emission computed tomography and dipyridamole infusion. Endothelial function was evaluated by assessing 1-min postischaemic flow-mediated dilatation of the brachial artery (FMD); nitroglycerine-mediated dilatation (NMD) of the same brachial artery was used as measure of nonendothelium-dependent vasodilatation. In approximately 1 year, we enrolled 21 subjects who met stringent inclusion criteria (47+/-10 years old, 26.6+/-2.8 kg/m2, 78% men). Five patients showed LVH. Multivariate analyses showed a significant negative correlation of LV mass index with FMD (beta=-0.61, P<0.05) but not with NMD, neither with CFR. Stress-corrected MWS showed independent correlation with CFR (beta=0.51, P<0.05). Thus, in clinically healthy, new discovered hypertensive subjects, never treated and mostly in the early stage of arterial hypertension, LVH can be associated with endothelial dysfunction while maximal dipyridamole- dependent CFR may be preserved; nevertheless, a cardiac phenotype presenting with tendency to impaired myocardial contractility, assessed by stress-corrected MWS, showed association with lower CFR in the early stage of arterial hypertension.

This study has been designed to evaluate the relationship among transforming growth factor beta1 (TGFbeta1) and some measurements of diastolic function in a population of hypertensive subjects with normal left ventricular ejection fraction. We studied 67 hypertensive outpatients who according to their BMI levels were subdivided into three groups: lean (L), overweight (OW) and obese (OB) hypertensives (HT). Circulating TGFbeta1 and M- and B-mode echocardiography was determined. All hypertensives were further subgrouped, according to European Society of Cardiology Guidelines, into two subsets of patients with normal diastolic function or with diastolic dysfunction. Prevalence of left ventricular hypertrophy (LVH) was determined in all the groups. TGFbeta1, left ventricular mass (LVM), LVM/h(2.7), E-wave deceleration time and isovolumic relaxation time (IVRT) were significantly (P < 0.005) higher and E/A velocity ratio was significantly (P < 0.05) lower in OW-HT and OB-HT than in L-HT. Prevalence of LVH was significantly higher (P < 0.03) in group OB-HT than in L-HT. TGFbeta1 (P < 0.004), LVM/h(2.7) (P < 0.001) and prevalence of LVH were (P < 0.01) significantly higher in hypertensives with diastolic dysfunction than hypertensives with normal diastolic function. TGFbeta1 levels were positively correlated with BMI (r = 0.60; P < 0.0001), LVM/h(2.7) (r = 0.28; P < 0.03), IVRT (r = 0.30; P < 0.02) and negatively with E/A ratio (r = -0.38; P < 0.002) in all HT. Multiple regression analysis indicated that TGFbeta1, BMI and IVRT were independently related to E/A ratio explaining 71% of its variability (r = 0.84; P < 0.0001). This relationship was independent of LVH, age and HR suggesting that TGFbeta1 overproduction may be considered a pathophysiological mechanism in the development of left ventricular filling abnormalities in obesity-associated hypertension.

The relationship between the increase in blood pressure and the incidence of cardiovascular disease is well recognized today. Studies have shown that more attention should be paid to systolic blood pressure (SBP) in relation to cardiovascular risk and that therapeutic interventions should preferably focus on reducing SBP. The antihypertensive efficacy of indapamide 1.5 mg sustained release (indapamide SR), a low-dose thiazide-type diuretic, was assessed on SBP. Three randomized, double-blind, controlled studies were conducted with indapamide SR, over a period of 3 to 12 months. Elderly patients or patients with target-organ damage, hypertension and left ventricular hypertrophy (LVH) (LIVE study) or with type II diabetes with microalbuminuria (NESTOR study) showed a decrease in SBP varying from 22.7 to 31.8 mmHg. The treatment with indapamide SR resulted in a better or equivalent control of SBP than treatment with a standard dose of a true thiazide diuretic (hydrochlorothiazide), a calcium channel blocker (amlodipine), and an angiotensin-converting enzyme inhibitor (enalapril). No therapeutic escape was observed. All treatments showed good acceptability with no unexpected adverse event. In conclusion, indapamide SR is very effective in lowering SBP-a major independent cardiovascular risk factor-notably in hypertensive high-risk patients with LVH, the elderly and diabetics, when compared to major antihypertensive treatments. This SBP-lowering effect is maintained over the long term.

Left ventricular hypertrophy (LVH) is a dominant characteristic of cardiovascular mortality. We investigated the interaction between physical activity and LVH on stroke mortality, based on a 40-year follow-up of the Corfu cohort from the Seven Countries Study. The population studied consisted of 529 rural men (40-59 years old) enrolled in the Study at 1961. LVH was electrographically confirmed according to Minnesota coding. Physical activity levels were assessed by self-reports of habitual, occupational and leisure-time activities. Cox proportional hazard models were used to evaluate exercise levels with respect to stroke mortality in people with and without LVH. During the follow-up, 461 (87%) died, and 74 (16%) of these deaths were due to stroke. LVH was present in 40 (7.5%) men. A total of 362 (68%) men were defined as physically active. Physical activity was associated with a lower risk of stroke (hazard ratio=0.65, P<0.05). On the other hand, LVH had 5.8-fold the risk of stroke (P<0.001) among sedentary and 4.5-fold the risk (P<0.001) among physically active men, after controlling for several potential confounders. However, moderate physical activity decreased the risk of stroke by 49% in men with LVH as compared to sedentary without LVH (hazard ratio=0.51, P<0.01), while hard exercise did not confer any significant reduction in stroke risk. We revealed the benefits from moderate physical activity on stroke mortality among men with LVH. Physicians and other health-care professionals should encourage patients with LVH to adopt a physically active lifestyle.

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study was designed to compare losartan- vs atenolol-based antihypertensive treatment on cardiovascular morbidity and mortality in a population of 9193 hypertensive patients with left ventricular hypertrophy (LVH). In LIFE, the losartan-based treatment further reduced the primary composite end point (cardiovascular death, myocardial infarction, or stroke) by 13% (risk reduction (RR) 0.87, 95% confidence interval (CI) 0.77-0.98, P=0.021). The further reduction in stroke with losartan (RR 0.75, 95% CI 0.63-0.89, P=0.001) was the major contributing factor to the reduction in the primary end point. Our objective was to project the reduction in stroke observed with a losartan- vs an atenolol-based antihypertensive treatment regimen in the LIFE study to the European Union (EU) population. The number of stroke events averted was estimated by identifying the number of persons in the EU expected to meet the LIFE inclusion criteria, and multiplying this figure by the cumulative incidence risk difference in stroke from LIFE at 5.5 years. The age- and gender-specific prevalence of hypertension, electrocardiographically (ECG)-diagnosed LVH among those with hypertension (inclusion criteria), and heart failure among those with LVH and hypertension (exclusion criteria) were applied to the EU census estimates. We conservatively projected that an estimated 7.8 million individuals aged 55-80 years in the EU are affected by hypertension and ECG-diagnosed LVH. Use of a losartan-based antihypertensive treatment in this population is projected to prevent approximately 125 000 first strokes over a 5.5-year period. A population-wide prevention strategy of using losartan in patients with LVH and hypertension has the potential to have a major public health impact by reducing the morbidity and mortality of stroke in the EU.

Electrocardiographic (ECG) left bundle branch block (LBBB) is associated with left ventricular hypertrophy (LVH), but its relation to left ventricular (LV) geometry and function in hypertensive patients with ECG LVH is unknown. Echocardiograms were performed in 933 patients (548 women, mean age 66+/-7 years) with essential hypertension and LVH by baseline ECG in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. LBBB, defined by Minnesota code 7.1, was present in 47 patients and absent in 886 patients. Patients with and without LBBB were similar in age, gender, body mass index, blood pressure, prevalence of diabetes, and history of myocardial infarction. Despite similarly elevated mean LV mass (126+/-25 vs 124+/-26 g/m(2)) and relative wall thickness (0.41+/-0.07 vs 0.41+/-0.07, P=NS), patients with LBBB had lower LV fractional shortening (30+/-6 vs 34+/-6%), ejection fraction (56+/-10 vs 61+/-8%), midwall shortening (14+/-2 vs 16+/-2%), stress-corrected midwall shortening (90+/-13 vs 97+/-13%) (all P<0.001), and lower LV stroke index (38+/-7 vs 42+/-9 ml/m(2)) (P<0.05). Patients with LBBB also had reduced LV inferior wall and lower mitral E/A ratio (0.75+/-0.18 vs 0.87+/-0.38) (all P<0.05). The above univariate results were confirmed by multivariate analyses adjusted for gender, age, blood pressures, height, weight, body mass index, heart rate, and LV mass index. Among hypertensive patients at high risk because of ECG LVH, the presence of LBBB identifies individuals with worse global and regional LV systolic function and impaired LV relaxation without more severe LVH by echocardiography.

The Losartan Intervention For End point reduction in hypertension (LIFE) study showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke, and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios (HR) in 4287 and 685 participants who reported intakes of 1-7 and >8 drinks/week at baseline, respectively, with those in 4216 abstainers, adjusting for gender, age, smoking, exercise, and race. Within categories, clinical baseline characteristics, numbers randomized to losartan and atenolol, and blood pressure (BP) lowering were similar on the drug regimens. Overall BP control (<140/90 mmHg) at end of follow-up was similar in the categories. Composite end point rate was lower with 1-7 (24/1000 years; HR 0.87, P<0.05) and >8 drinks/week (26/1000 years; HR 0.80, NS) than in abstainers (27/1000 years). Myocardial infarction risk was reduced in both drinking categories (HR 0.76, P<0.05 and HR 0.29, P<0.001, respectively), while stroke risk tended to increase with >8 drinks/week (HR 1.21, NS). Composite risk was significantly reduced with losartan compared to atenolol only in abstainers (HR 0.81 95% confidence interval, CI (0.68, 0.96), P<0.05), while benefits for stroke risk reduction were similar among participants consuming 1-7 drinks/week (HR 0.73, P<0.05) and abstainers (HR 0.72, P<0.01). Despite different treatment benefits, alcohol-treatment interactions were nonsignificant. In conclusion, moderate alcohol consumption does not change the marked stroke risk reduction with losartan compared to atenolol in high-risk hypertensives. Alcohol reduces the risk of myocardial infarction, while the risk of stroke tends to increase with high intake.

Conventional definitions of left ventricular (LV) hypertrophy do not account for interindividual differences in loading conditions. We may define LV mass as inappropriately high when exceeding 128% of theoretical values predicted by gender, height(2.7), and stroke work, which explain up to 82% of the variability of LV mass in normal reference subjects. In 652 participants in the Losartan Intervention For Endpoint reduction in hypertension study without clinically overt cardiovascular disease or diabetes, we investigated whether inappropriately high LV mass is associated with relevant LV abnormalities independent of traditional definition of LV hypertrophy (ie, LV mass index >116 g/m(2) in men and >104 g/m(2) in women). The study sample was divided into three groups: patients with inappropriately high LV mass but without LV hypertrophy were compared to patients with LV hypertrophy and to patients with appropriate LV mass and without LV hypertrophy. Patients with inappropriately high but nonhypertrophic LV mass had higher body mass index and relative wall thickness, and lower LV myocardial systolic function, than patients with appropriate LV mass or patients with LV hypertrophy. In multivariate analyses, inappropriately high LV mass was independently associated with lower myocardial systolic function independent of LV hypertrophy and other covariates. Inappropriately high LV mass was also associated with prolonged isovolumic relaxation time and lower mitral E/A ratio independent of covariates. In conclusion, inappropriately high LV mass was associated with relevant, often preclinical, manifestations of cardiac disease in the absence of traditionally defined echocardiographic LV hypertrophy and concentric geometry.

We wanted to investigate whether urine albumin/creatinine ratio (UACR) and left ventricular (LV) mass, both being associated with diabetes and increased blood pressure, predicted cardiovascular events in patients with hypertension independently. After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 960 hypertensive patients from the LIFE Echo substudy with electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were measured to calculate UACR. The patients were followed for 60+/-4 months and the composite end point (CEP) of cardiovascular (CV) death, nonfatal stroke or nonfatal myocardial infarction was recorded. The incidence of CEP increased with increasing LV mass (below the lower quartile of 194 g to above the upper quartile of 263 g) in patients with UACR below (6.7, 5.0, 9.1%) and above the median value of 1.406 mg/mmol (9.7, 17.0, 19.0%(***)). Also the incidence of CV death increased with LV mass in patients with UACR below (0, 1.4, 1.3%) and above 1.406 mg/mmol (2.2, 6.4, 8.0%(**)). The incidence of CEP was predicted by logUACR (hazard ratio (HR)=1.44(**) for every 10-fold increase in UACR) after adjustment for Framingham risk score (HR=1.05(***)), history of peripheral vascular disease (HR=2.3(*)) and cerebrovascular disease (HR=2.1(*)). LV mass did not enter the model. LogUACR predicted CV death (HR=2.4(**)) independently of LV mass (HR=1.01(*) per gram) after adjustment for Framingham risk score (HR=1.05(*)), history of diabetes mellitus (HR=2.4(*)) and cerebrovascular disease (HR=3.2(*)). (*)P<0.05, (**)P<0.01, (***)P<0.001. In conclusion, UACR predicted CEP and CV death independently of LV mass. CV death was predicted by UACR and LV mass in an additive manner after adjustment for Framingham risk score and history of CV disease.

It has been clearly demonstrated that ageing and arterial hypertension are both associated with an increased prevalence of left ventricular hypertrophy (LVH), which is a powerful risk factor for cardiovascular (CV) events. The objective of this study was to assess the impact of echocardiographic LVH in profiling the absolute CV risk stratification according to the 1999 World Health Organization-International Society of Hypertension (WHO/ISH) guidelines in elderly hypertensive patients. A total of 223 never-treated elderly patients (> or =65 years) with essential hypertension (98 men, 125 women, mean age 72+/-5 years) referred to our outpatient hospital clinic were included in the study. They underwent the following procedures: (1) medical history, physical examination, and clinic blood pressure; (2) routine blood chemistry and urine analysis and (3) electrocardiogram. The risk was initially stratified according to the routine procedures suggested by WHO/ISH guidelines and subsequently reassessed by adding the results of echocardiography (LVH as left ventricular mass index >51 g/m(2.7) in men and >47g/m(2.7) in women). According to routine classification, 56% (n=125) were medium-risk patients, 29% (64) high-risk and 15% (34) very-high-risk patients. The overall prevalence of LVH was 56% (48% in medium-risk and 62% in high-risk or very-high-risk patients, P<0.01). A marked change in risk stratification was observed when echocardiographic LVH was taken into consideration: medium-risk patients decreased to 29% and high-risk patients rose to 56% (P<0.01). In conclusion, ultrasound assessment of cardiac target organ damage is extremely useful in obtaining a more valid assessment of global cardiovascular risk in elderly hypertensives, because stratification based on diagnostic routine procedures can underestimate the overall risk in a large fraction (48%) of medium-risk subjects.

We sought in this study to examine the relationship between microalbuminuria and cardiac geometry since a slight increased urinary albumin excretion (UAE) and increased left ventricular (LV) mass have both been identified as predictors of cardiovascular events in hypertensive subjects. For this purpose, microalbuminuria was determined in three non-consecutive 24-h urine samples as UAE of 20-200 mg/24 h in a group of 249 untreated hypertensive subjects. Echocardiographic classification of patients into LV geometric patterns was based on relative wall thickness values and on gender-specific values for LV mass index (LVMI). The group of patients with microalbuminuria (n = 119) was matched for age, sex, body mass index, smoking status and plasma cholesterol level with the group of patients without microalbuminuria (n = 130). Subjects with microalbuminuria had significantly increased LVMI (111 vs 90 g/m(2), P < 0.0001), relative wall thickness (0.46 vs 0.41, P < 0.001) and office systolic and diastolic blood pressure (161 vs 148 and 101 vs 97 mmHg, respectively, P < 0.005). For the pooled population, UAE was positively correlated to LVMI (r = 0.46, P < 0.001) and relative wall thickness (r = 0.47, P < 0.001). In the entire population, normal LV geometry, concentric LV remodelling, eccentric and concentric LV hypertrophy was found in 34%, 33%, 12% and 21%, respectively. The prevalence of normal LV geometry was significantly higher in normoalbuminuric compared with microalbumnuric subjects (55 vs 14%, P < 0.001) while the prevalence of concentric LV hypertrophy was significantly higher in microalbuminuric compared with normoalbuminuric subjects (32 vs 5%, P < 0.0001). Multiple regression analysis revealed that concentric LV hypertrophy was significantly associated with increased values of UAE and mean arterial pressure. In conclusion, the higher prevalence of unfavourable LV geometric patterns in hypertensive subjects with microalbuminuria compared with those without microalbuminura, may account for the worse cardiovascular outcomes associated with the presence of an increased UAE in hypertensive subjects.

Objective: The aim of the study was to compare the efficacy and safety of two stress echocardiography methods, exercise and dobutamine, in the diagnosis of coronary artery disease in hypertensive patients with angina., Patients and Methods: A total of 197 treated hypertensive patients, age 53 +/- 9 years (65 women) with no history of myocardial infarction referred for coronary angiography were prospectively investigated with exercise electrocardiography (ECG), exercise and dobutamine echocardiography., Results: Sensitivity of the exercise ECG, exercise echocardiography and dobutamine echocardiography did not differ (77%, 82% and 75%). Negative predictive value of exercise ECG was significantly lower than exercise echocardiography (64% vs 79%, P < 0.01). Specificity and positive predictive value of exercise ECG were markedly lower than exercise and dobutamine echocardiography (57%, 96%, 98% and 72%, 97%, 98%, P < 0.0001 for both stress echocardiography vs ECG). Specificity and sensitivity of diagnostic methods were not influenced by the presence of echocardiographic left ventricular hypertrophy. Dobutamine infusion in comparison to exercise was more often associated with substantial arterial blood pressure rise or fall (7% vs 2%, P < 0.05) and with simple ventricular ectopy (15,7% vs 6,1%, P < 0.05)., Conclusions: In hypertensive patients with the symptoms of angina, both stress echo methods are significantly more specific than the exercise ECG test. Maximal exercise is associated with less frequent side effects than infusion of dobutamine, so exercise echocardiography may be preferred in the diagnosis of angina in hypertensive patients.

Increased QT dispersion has been associated with ventricular arrhythmia and sudden death in a variety of cardiac disorders. Left ventricular hypertrophy (LVH) has also been associated with increased incidence of sudden cardiac death in patients with essential hypertension. Furthermore, patients with essential hypertension, particularly those with LVH, are more likely to develop ventricular arrhythmias than are the normal population. The relationship between LVH, QT dispersion, complex ventricular arrhythmia and sudden cardiac death in previously untreated patients over long-term follow-up in hypertension has not been reported before and is the purpose of this study. Fifty-nine adult subjects with essential hypertension, who had never been previously on antihypertensive treatment were followed up for a total of 119.2 +/- 26.2 months. QTc (corrected QT), blood pressure, electrocardiograms, and 24-h Holter ECG recordings were performed in all patients at the time of entry to the study. Ventricular arrhythmias were classified using a modified Lown's scoring system. During the follow-up period death occurred in 12 cases (20%) of which only six (10%) deaths were sudden. The findings of this study indicate that LVH and complex ventricular arrhythmias (Lown's score > or =3) are the only significant predictors of sudden death. Although patients who died suddenly had higher systolic and diastolic blood pressures and greater QTc dispersion compared to surviving patients, this difference was statistically not significant. Similarly, when those who died suddenly were compared to those non-cardiac deaths, LVH and complex ventricular arrhythmias were the only significant predictors of sudden death. In spite of increased QTc dispersion in hypertensive patients, this finding was not associated with increased risk of sudden death and only LVH and high grade ventricular arrhythmias identified hypertensive patients at risk of sudden cardiac death over a 10-year follow-up period.

Background: Hypertensive patients with left ventricular hypertrophy (LVH) need a prompter and more intensive pharmacological treatment than subjects without evidence of cardiac involvement. So the detection of LVH plays an important role for decision-making in hypertensives., Objective: To evaluate the impact of different echocardiographic criteria to define LVH in a more precise stratification of absolute cardiovascular risk in hypertensives without target organ damage (TOD) as assessed by routine investigations., Methods: A total of 100 never treated patients with grade 1 and 2 essential hypertension (53 men, 47 women, age 44 +/- 12 years) referred for the first time to our outpatient clinic were included in the study. They underwent the following procedures: (1) family and personal medical history, (2) clinic blood pressure (BP) measurement, (3) routine blood chemistry and urine analysis, (4) electrocardiogram, (5) echocardiogram. Risk was stratified according to the criteria suggested by the 1999 WHO-ISH guidelines. TOD was initially evaluated by routine procedures only, and subsequently reassessed by using six different echocardiographic criteria to recognise LVH: (a) left ventricular mass index (LVMI) >120 g/m(2) in men and 100 g/m(2) in women; (b) 125 g/m(2) in men and 110 g/m(2) in women; (c) 134 g/m(2) in men and 110 g/m(2) in women; (d) 125 g/m(2) in men and 125 g/m(2) in women; (e) 51 g/m(2.7) in men and 47 g/m(2.7) in women; (f) 126 g/m in men and 105 g/m in women., Results: According to the first classification based on routine investigations, 46% were low risk and 54% were medium risk patients. Significant changes in risk stratification were obtained when LVH was assessed by echocardiography. A percentage of patients, ranging from 9 (f) to 25% (d), were found to having LVH according to different criteria, and consequently moved from low and medium risk strata to high risk stratum., Conclusions: The detection of LVH by echocardiography allowed a much more accurate identification of high risk patients. In particular our results suggest that: (1) cardiovascular risk stratification only based on a simple routine work-up can often underestimate overall risk; (2) a better standardisation in defining LVH is needed, considering that the impact of cardiac hypertrophy on risk stratification is markedly dependent on the echocardiographic criteria used to diagnose it.

Left ventricular (LV) mass relates positively and continuously to cardiac mortality and thus its regression is a rational therapeutic aim. Whilst the office blood pressure (BP) relates poorly to LV mass, it was unclear whether the 24-h ambulatory BP or the exercise systolic BP (ExSBP) was the stronger correlate of LV structural indices. We studied 49 hypertensive patients with a mean age of 45 (s.d. 12) years with a mean body mass index of 27.1(3.9) kg/m(2). The mean (s.d.) of office BP, ambulatory BP and ExSBP measured at the end of the first three stages of Bruce protocol treadmill exercise I, II and III were 161(20)/99(10), 140(13)/89(10), 190(30), 198(30) and 201(33) mm Hg respectively. The LV indices measured echocardiographically were LV septal thickness (IVSd) (1.1(0.2) cm), LV posterior wall thickness (LVPWd) (1.0(0.1) cm) and LV mass indexed to body surface area (LVMI) (123(30) g/m(2)). Age and gender (male) had the highest correlations with the LV indices. Of the BP measures, the stage II ExSBP's correlation with the LV indices was consistently higher than all other ExSBP, office systolic BP and 24-h systolic ambulatory BP. In a stepwise multiple regression analysis on IVSd, after adjusting for age and gender, the stage II ExSBP was independently associated with IVSd (beta= 0.018 (s.e. 0.008), P = 0.024). When only BP measures were considered as explanatory variables only stage II ExSBP was a significant predictor (P = 0.0001) of IVSd as was the case with LVPWd (P = 0.006) and LVMI (P = 0.0008). Submaximal exercise BP measured at a workload comparable to physical activity encountered in daily life correlated more closely with the left ventricular wall thickness and mass. The exercise BP should perhaps be normalised in hypertension management to optimise regression of LV hypertrophy.

Over the past decade, an expanding body of epidemiological and clinical trial data has been collated, culminating in the development of guidelines designed to help physicians make decisions about intervention and the intensity of treatment, based on objective assessments of the overall level of risk for cardiovascular disease. However, guidelines are not prescriptive and allow physicians leeway in interpretation. Thus, it is of clinical interest to explore some of the issues that may influence the use of these guidelines in clinical practice. This paper summarises a round table panel discussion that highlighted the usefulness of current guidelines, but also demonstrated that these guidelines, and the evaluation of cardiovascular risk, need to be used with care and always interpreted in the light of sound clinical judgement.

In the hypertensive patient with electrocardiographic and/or echocardiographic evidence of left ventricular hypertrophy, exercise electrocardiography lacks sensitivity and specificity for the detection of obstructive coronary artery disease and should be avoided. In comparative studies both myocardial perfusion imaging and stress echocardiography are significantly more sensitive and specific for the detection of significant obstructive coronary artery disease, in the presence of left ventricular hypertrophy, and are the investigations of choice.

The aim of this study was to evaluate whether salt-sensitivity in essential hypertension produces a significant comparative difference in diastolic function and ventricular mass when compared with sodium-resistance. Recent epidemiological data have demonstrated a positive correlation between sodium intake and arterial pressure. Furthermore, a positive correlation has been detected between sodium intake and left ventricular hypertrophy (LVH) independently of arterial pressure. Thirty-one patients who had never been treated before for uncomplicated hypertension were studied. Each subject received a 30 mmol/per day sodium diet for 14 days, supplemented with a further 190 mmol of sodium in the first study week (220 mmol for the first 7 days and 30 mmol for the second 7 days). Throughout the study compliance was assessed by measuring daily urinary sodium excretion. Sodium sensitivity of blood pressure was defined as the difference (5% or more) between blood pressure at the end of the low and high sodium intake periods. On this basis 16 patients were defined as salt-sensitive (SS) and 15 patients as salt-resistant (SR). The two groups were homogeneous for age, sex and race. Baseline mean arterial pressure (MAP) was comparable between SS (108 +/- 1.8 mm Hg) and SR (107 +/- 2.1 mm Hg, P = NS). Each patient was submitted to M-MODE and two-dimensional echocardiogram studies in order to estimate left ventricular mass using the Penn conventional formula and parameters of left ventricular diastolic function. The left ventricular mass measurement showed higher values in the SS group although this did not reach statistical significance (118.4 +/- 4.4 vs 112.0 +/- 4.2 gr/mq, P = NS). Both interventricular septal and posterior wall thickness did not demonstrate significant differences between the two groups. The salt-sensitive group showed impaired left ventricular diastolic function; in particular, the first diastolic peak representing the early maximum of diastolic filling velocity (E) was lower in SS subjects than in SR subjects (71.6 +/- 2.9 vs83.1 +/- 3.3 cm/sec, P < 0.02). No significant difference was detected in the second peak representing the atrial maximum of filling velocity (A) (69.0 +/- 2.3 vs 66.0 +/- 2.0 cm/sec, P = NS). As a consequence the E/A ratio was significantly different (0.73 +/- 0.2 in the SR vs 1.2 +/- 0.04 in the SS group, P < 0.05). Moreover, the peak E integral was lower in SS than in SR subjects (8. 7 +/- 0.6 vs11.2 +/- 0.5 cm, P < 0.005; no difference for the peak A integral (6.0 +/- 0.3 vs 5.7 +/- 0.4 cm, P = NS). The E peak deceleration time was significantly reduced in the SS group (400.3 +/- 13.5 vs 500.9 +/- 12.8 cm/sec, P < 0.001). No significant difference was found for the isovolumetric relaxation time (IVRT) (95.7 +/- 4.3 vs 92.2 +/- 4.0, P = NS). Our data show an impaired diastolic function expressed by a reduced early diastolic filling velocity (peak E) and a significantly abnormal E/A ratio in SS in comparison with SR subjects. Therefore abnormalities in diastolic function are detectable earlier in SS hypertensive subjects than in SR irrespective of actual MAP.

Objective: The aim of the study was to determine the potential influence of hypertension overlapping hypertrophic cardiomyopathy (HCM) on left ventricular hypertrophy (LVH) pattern. We compared the magnitude of LVH asymmetry between younger and older patients with HCM and concomitant hypertension., Material and Methods: We studied 18 patients (age range from 18 to 77 years) in whom HCM was accompanied by mild-to-moderate hypertension. Patients were subdivided into two groups: (I) <50 years of age (11 patients); and (II) >50 years of age (seven patients). The thickness of ventricular septum and posterior wall was assessed by M-mode echocardiography. The pattern of LVH was determined based on the value of ventricular septum/posterior wall thickness (VS/PW) ratio and LVMI was calculated according to Devereux formula., Results: The more asymmetric LVH pattern was revealed in older HCM with hypertension patients than in younger patients (VS/PW thickness ratio 2.62 +/- 0.81 vs 1.58 +/- 0.56, P < 0.05). The LVMI was similar in both groups (210 + 87 vs 191 + 30 g/m2, P > 0.5)., Conclusion: Asymmetric pattern of LVH aggravated with increasing age in HCM with hypertension patients while LVMI was comparable between younger and older patients. Thus, the primary myocardial disease, ie, HCM, so significantly determined the asymmetric LVH pattern with aging that coexistent hypertension was not a sufficiently strong stimulus to alter LVH pattern into a more concentric one in the elderly.

To investigate carotid haemodynamic characteristics in essential hypertensive patients with left ventricular hypertrophy, we evaluated the structure and function as well as blood flow of the common carotid artery by using a combination of B-mode ultrasound and pulsed-Doppler in control subjects (n = 38), and hypertensive patients with (n = 40) and without (n = 27) left ventricular hypertrophy. Hypertensive patients had a higher intima-medial thickness compared with control subjects. Diastolic/systolic flow velocity ratio as well as flow volume ratio was significantly decreased in hypertensive patients with left ventricular hypertrophy in association with decline of distensibility of the common carotid artery. In the hypertensive patients with left ventricular hypertrophy, diastolic/systolic flow velocity ratio as well as flow volume ratio had significant correlation with diastolic blood pressure, pulse pressure and carotid arterial distensibility. These findings indicate that diastolic blood flow in the common carotid artery is impaired in hypertensive patients with left ventricular hypertrophy. Decreased distensibility and low diastolic perfusion pressure may be the underlying mechanisms.

There are strong experimental evidences that alpha 1-adrenergic stimulation significantly influences cardiac arrhythmogenesis, especially during myocardial ischaemia and reperfusion. However, anti-arrhythmic effects of alpha-blockade in humans were scarcely utilised. Thus the purpose of our study was to assess these effects in patients with phaeochromocytoma. In 22 patients simultaneous 24 h ECG and blood pressure (BP) monitoring, as well as estimation of the urinary 24 h free catecholamine excretion, were performed twice: before and during the treatment with the non-selective alpha-blocker, phenoxybenzamine. The heart rate variability was measured during four 5 min periods, at 10.00, 16.00, 22.00 and 04.00. During alpha-blockade systolic blood pressure (SBP) decreased from 137.6 +/- 23.8 to 126.5 +/- 15.7 mm Hg (P < 0.01), heart rate increased from 83.0 +/- 9.9 to 88.5 +/- 10.0/min (P < 0.02) and duration of QTc interval unsignificantly increased. Incidence of frequent or repetitive ventricular arrhythmias was significantly higher before treatment (in 9 vs 3 of 22 patients, P < 0.05). Heart rate variability significantly decreased during the treatment, with regard to all parameters, representing both the sympathetic and parasympathetic activity. We conclude that non-selective alpha-blockade significantly decreases the incidence of frequent or repetitive ventricular arrhythmias in patients with phaeochromocytoma, although the lack of QTc interval shortening suggests that the effect of class I drugs may participate in the anti-arrhythmic effects of phenoxybenzamine. Moreover, non-selective alpha-blockade in phaeochromocytoma significantly diminishes vagal activity.

Left ventricular hypertrophy is a frequent and prognostically unfavourable finding in patients with essential hypertension and has been found to be a predictor for the development of essential hypertension in normotensive subjects. Among various genetic, haemodynamic and humoral determinants, dietary salt intake has been demonstrated to influence left ventricular mass in hypertensive disease. Several cross-sectional studies have shown a close relation between dietary salt intake and parameters of left ventricular hypertrophy. Moreover, reduction of dietary sodium intake was associated with a decrease of left ventricular mass in a prospective study. The underlying mechanism of how salt intake modulates myocardial structure has not been explained yet. Three possible explanations are discussed: (1) sodium influences left ventricular mass via raised preload, (2) the sympathetic nervous system acts as a mediator, and (3) the renin-angiotensin-aldosterone system is the responsible link. Recent animal experiments and clinical studies suggest that the renin-angiotensin-aldosterone system may mediate both the cardiotrophic and the blood pressure raising effects of salt. However, not all individuals have a similar high susceptibility to blood pressure elevation develop left ventricular hypertrophy when exposed to high salt intake. We suggest that the underlying mechanism is a dysregulation of the renin-angiotensin-aldosterone system. Some individuals may have an impaired downregulation of angiotensin II synthesis when challenged with high salt intake. Accordingly, we found that relatively too high levels of angiotensin II in relation to urinary sodium excretion were associated with left ventricular hypertrophy in these individuals on high salt intake.

Left ventricular hypertrophy is now recognised to be an important risk factor associated with such adverse cardiovascular events as myocardial infarction, heart failure, stroke and sudden cardiac death. This is true for the general population and those with uncomplicated hypertension. Herein the what, why and how of hypertensive heart disease (HHD) is reviewed: what is it, why does a structural remodelling of the myocardium occur and how can it be prevented on the one hand or regressed on the other. Clinical and experimental studies are presented to address each of these issues.

The aim of the present longitudinal study was to describe determinants of blood pressure (BP) and echocardiographically calculated left ventricular mass in adolescents with a variable risk of future hypertension. BP was measured and M-mode echocardiography was performed in 52 children, 29 male and 23 female, at a mean age of 12.6 +/- 1.5 years. A re-examination was performed after 5.6 years. Thirty-six children were born to mothers who had hypertension during pregnancy whereas 16 children were born after a normotensive pregnancy. During follow-up a difference in body weight (P < 0.01) and height (P < 0.001) developed between male and female subjects. At the same time a difference in systolic blood pressure (SBP) appeared between sexes (P < 0.01). At follow-up there were significant correlations between sex and SBP (r = 0.37, P < 0.01) and left ventricular mass (r = 0.54, P < 0.001). In multivariate analyses sex emerged as a factor explaining the variance of both SBP and left ventricular mass at follow-up. In conclusion a difference in BP between male and female subjects emerges concomitantly with differences in body size during adolescence. An independent influence of sex on both BP and left ventricular mass appears in parallel with this.

To clarify a possible relationship between the level of BP and signs of myocardial ischaemia, two groups of treated hypertensive patients with (n = 12) and without (n = 18) increased left ventricular mass defined by echocardiography were investigated with 24h ambulatory BP and ECG monitoring. It was found that hypertensive patients with increased left ventricular mass had the following. (1) Higher systolic BP, heart rate (HR) and SBP x HR product during the night indicating a higher ventricular work load than hypertensives without increased LVM in this period. (2) This increased left ventricular work load during the night was concomitant with a lower DBP consistent with a lower perfusion pressure of the left ventricular myocardium. (3) Significantly depressed ST segment levels throughout the 24 hours with a significant positive correlation between BP and the level of the ST segment indicating increased ischaemic metabolic changes within the myocardium the lower the BP. (4) A higher ratio between the systolic SBP x HR product and DBP during sleep than in hypertensives without increased left ventricular mass, further corroborating that low DBP during the night might cause ischaemia through an imbalance between left ventricular work load and coronary perfusion pressure. We conclude that low BPs in hypertensive patients with increased left ventricular mass seem to induce ischaemia of the left ventricle. These findings provide a possible mechanism for the increased risk of ischaemic heart disease in hypertensive patients with low achieved BP.