G. de Simone

Relation of obesity and gender to left ventricular hypertrophy in normotensive and hypertensive adults.

Although it is recognized that both hypertension and obesity are associated with increased left ventricular mass, the relative impacts of obesity, arterial hypertension, and gender on the prevalence of ventricular hypertrophy remain uncertain. Accordingly, echocardiographic left ventricular mass normalized for height to the power of the allometric or growth relation between ventricular mass and height was compared in 164 normotensive subjects (85 men [24 obese] and 79 women [28 obese], aged 45 +/- 12 years) and 475 hypertensive patients (325 men [126 obese] and 150 women [85 obese], aged 54 +/- 10 years) from an adult employed population. Gender-specific upper normal limits were used to identify ventricular hypertrophy. Left ventricular mass/height 2.7 was higher in obese than normal-weight normotensive subjects (P < .004) independently of the level of blood pressure and identified a higher prevalence of hypertrophy (mainly eccentric) in obese than in normal-weight normotensive subjects (14% versus 5%, P < .04), a difference that was not detected by left ventricular mass/body surface area. Left ventricular mass/height identified hypertrophy in 52% of obese and 30% of normal-weight hypertensive patients (P < .0001) because of higher prevalences in obese than normal-weight patients of both eccentric (34% versus 20%) and concentric ventricular hypertrophy (18% versus 10%). The increase in left ventricular mass was independent of blood pressure values in obese normotensive women (but not men), and the prevalence of supranormal left ventricular mass/height 2.7 was even higher in hypertensive obese women (58%) than men (49%).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac abnormalities in young women with anorexia nervosa.

OBJECTIVE--To identify the characteristics of cardiac involvement in the self-induced starvation phase of anorexia nervosa. METHODS--Doppler echocardiographic indices of left ventricular geometry, function, and filling were examined in 21 white women (mean (SD) 22 (5) years) with anorexia nervosa according to the DSMIII (Diagnostic and Statistical Manual of Mental Disorders) criteria, 19 women (23 (2) years) of normal weight, and 22 constitutionally thin women (21 (4) years) with body mass index < 20. RESULTS--13 patients (62%) had abnormalities of mitral valve motion compared with one normal weight woman and two thin women (p < 0.001) v both control groups). Left ventricular chamber dimension and mass were significantly less in women with anorexia nervosa than in either the women of normal weight or the thin women, even after standardisation for body size or after controlling for blood pressure. There were no substantial changes in left ventricular shape. Midwall shortening as a percentage of the values predicted from end systolic stress was significantly lower in the starving patients than in women of normal weight: when endocardial shortening was used as the index this difference was overestimated. The cardiac index was also significantly reduced in anorexia nervosa because of a low stroke index and heart rate. The total peripheral resistance was significantly higher in starving patients than in both control groups. The left atrial dimension was significantly smaller in anorexia than in the women of normal weight and the thin women, independently of body size. The transmitral flow velocity E/A ratio was significantly higher in anorexia than in both the control groups because of the reduction of peak velocity A. When data from all three groups were pooled the flow velocity E/A ratio was inversely related to left atrial dimension (r = -0.43, p < 0.0001) and cardiac output (r = -0.64, p < 0.0001) independently of body size. CONCLUSIONS--Anorexia nervosa caused demonstrable abnormalities of mitral valve motion and reduced left ventricular mass and filling associated with systolic dysfunction.

Left ventricular mass reduction during salt depletion in arterial hypertension.

Long-term therapy with antihypertensive agents that reduce sympathetic nervous system activity has been demonstrated by echocardiographic measurements to reverse left ventricular hypertrophy. This investigation evaluated the effects of salt depletion obtained by both chlorthalidone (25 mg/day) and severe restriction of salt intake (about 1016 mg Na+/day) on left ventricular mass (LVM) in as short a time as 12 weeks. Before the study, the patients had been off medication and on a balanced diet without salt restriction for at least 2 weeks; they were then randomly allocated to either the diuretic or low-salt regimen for 6 weeks and finally to alternative treatment according to a crossover model. Blood pressure, body weight, myocardial mass, and noninvasive measurements of left ventricular function (LVF) were determined at baseline and at the end of both periods of treatment. Results were evaluated by two-way analysis of variance in randomized blocks. Systolic and diastolic blood pressure and LVM were significantly and similarly reduced by diuretic therapy or salt restriction. A significant correlation was demonstrated between noninvasive measurements of LVM, expressed as cross-sectional area, and systolic blood pressure. No impairment of LVF could be detected over the treatment period.

Partial deficiency of adrenal 11-hydroxylase. A possible cause of primary hypertension.

Results of supraphysiological adrenocorticotropic hormone (ACTH) stimulation of biosynthetic pathways of adrenal zona fasciculata indicate that a deficiency of 11-hydroxylase exists in patients with essential hypertension. The deficiency is suggested by the much greater stimulus of synthesis of deoxycorticosterone (DOC) and deoxycortisol in hypertensive subjects than in controls (p less than 0.001). No significant difference in the synthesis of cortisol, corticosterone, progesterone, 17-hydroxyprogesterone (17-OHP), and delta-4-androstenedione (D4) was observed between the two groups. The ratios for synthesis of DOC and corticosterone and for deoxycortisol and cortisol found in hypertensive patients were significantly higher than those found in controls (p less than 0.001); no significant difference was observed in the synthesis of 17-OHP and progesterone. The synthesis of DOC and deoxycortisol was not significantly correlated with either blood pressure or plasma renin activity. Plasma renin activity was significantly lower in hypertensive subjects than in normotensive subjects (p less than 0.0001), while no difference was found in aldosterone secretion between the two groups. The 11-hydroxylase deficiency in the adrenal zona fasciculata may be one of the genetic factors causing hypertension together with environmental factors (particularly salt intake and work-related stress). The investigation performed in our study may be useful for the evaluation of adrenal zona fasciculata enzymatic activities during the study of hypertensive patients.

Metabolic syndrome and left ventricular hypertrophy in the prediction of cardiovascular events: the Strong Heart Study.

BACKGROUND AND AIMS Metabolic syndrome (MetS) is associated with increased prevalence of echocardiographic LV hypertrophy (LVH), a potent predictor of cardiovascular (CV) outcome. Whether MetS increases risk of CV events independently of presence of LVH has never been investigated. It is also unclear whether LVH predicts CV risk both in the presence and absence of MetS. METHODS AND RESULTS Participants in the 2nd Strong Heart Study examination without prevalent coronary heart disease, congestive heart failure or renal insufficiency (plasma creatinine >2.5mg/dL) were studied (n=2758; 1746 women). MetS was defined by WHO criteria. Echocardiographic LV hypertrophy was defined using population-specific cut-point value for LV mass index (>47.3g/m(2.7)). After controlling for age, sex, LDL-cholesterol, smoking, plasma creatinine, diabetes, hypertension and obesity, participants with MetS had greater probability of LVH than those without MetS (OR=1.55 [1.18-2.04], p<0.002). Adjusted hazard of composite fatal and non-fatal CV events was greater when LVH was present, in participants without (HR=2.03 [1.33-3.08]) or with MetS (HR=1.64 [1.31-2.04], both p<0.0001), with similar adjusted population attributable risk (12% and 14%). After adjustment for LVH, risk of incident CV events remained 1.47-fold greater in MetS (p<0.003), an effect, however, that was not confirmed when diabetic participants were excluded. CONCLUSION LVH is a strong predictor of composite 8-year fatal and non-fatal CV events either in the presence or in the absence of MetS and accounts for a substantial portion of the high CV risk associated with MetS.

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

The relation of metabolic syndrome (MetS) with cardiovascular outcome may be less evident when preclinical cardiovascular disease is present. We explored, in a post hoc analysis, whether MetS predicts cardiovascular events in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. MetS was defined by ⩾2 risk factors plus hypertension: body mass index ⩾30 kg/m2, high-density lipoprotein (HDL)-cholesterol <1.0/1.3 mmol/l (<40/50 mg/dl) (men/women), glucose ⩾6.1 mmol/l (⩾110 mg/dl) fasting or ⩾7.8 mmol/l (⩾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 (1591 (19.3%) of 8243 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.

Left ventricular geometry in obesity: Is it what we expect?

Obesity is characterized by the disproportionate growth of the components of body size, including adipose tissue and lean body mass. Left ventricular (LV) hypertrophy often develops, due to the coexistence of hemodynamic (cardiac workload) and non-hemodynamic components (including body composition and activity of visceral fat). While the hypertrophy of cardiomyocytes is produced by the hemodynamic load, through sarcomeric replication, there is a parallel growth of non-muscular myocardial components, including interstitial fat infiltration and accumulation of triglycerides in the contractile elements, which are thought to influence LV geometric pattern. Thus, pure intervention on hemodynamic load is unlikely to result in effective reduction of LV hypertrophy in obese. We review pathophysiology and prevalence of LV hypertrophy in obesity, with specific attention to LV geometric abnormalities and relations with body size.

Left ventricular hypertrophy associated with hypertension and its relevance as a risk factor for complications.

&NA; Recent research indicates that the level of left ventricular (LV) mass, commonly measured by echocardiography, reflects the combined effects of a variety of factors involved in the pathophysiology of hypertension, including obesity, blood pressure responses to everyday activity, high sodium intake and blood viscosity, the volume work load of the heart, and genetic factors predisposing to hypertension. Prospective studies indicate that LV mass is a stronger predictor of subsequent morbid events and death than blood pressure or other conventional risk factors except age. Preliminary findings of close relations between LV mass and arterial disease and between the change in LV mass during antihypertensive treatment and subsequent events contribute to explaining the strong predictive value of LV mass. Further research is needed to clarify the biologic basis of these observations and to determine whether stratification of hypertensive patients based on their level of LV mass can improve the treatment of hypertension.

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

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

Serum uric acid does not predict incident metabolic syndrome in a population with high prevalence of obesity

AIM To evaluate whether uric acid (UA) predicts 4-yr incidence of metabolic syndrome (MetS) in non-diabetic participants of the Strong Heart Study (SHS) cohort. METHODS AND RESULTS In this population-based prospective study we analyzed 1499 American Indians (890 women), without diabetes or MetS, controlled during the 4th SHS exam and re-examined 4 years later during the 5th SHS exam. Participants were divided into sex-specific tertiles of UA and the first two tertiles (group N) were compared with the third tertile (group H). Body mass index (BMI = 28.3 ± 7 vs. 31.1 ± 7 kg/m(2)), fat-free mass (FFM = 52.0 ± 14 vs. 54.9 ± 11 kg), waist-to-hip ratio, HOMA-IR (3.66 vs. 4.26), BP and indices of inflammation were significantly higher in group H than in group N (all p < 0.001). Incident MetS at the time of the 5th exam was more frequent in group H than group N (35 vs. 28%, OR 1.44 (95% CI = 1.10-1.91; p < 0.01). This association was still significant (OR = 1.13, p = 0.04) independently of family relatedness, sex, history of hypertension, HOMA-IR, central adiposity and renal function, but disappeared when fat-free mass was included in the model. CONCLUSIONS In the SHS, UA levels are associated to parameters of insulin resistance and to indices of inflammation. UA levels, however, do not predict incident MetS independently of the initial obesity-related increased FFM.