Francesca Pezzutto

Plasma Glucose Levels and Left Ventricular Diastolic Function in Nondiabetic Hypertensive Patients

BACKGROUND Changes in left ventricular (LV) diastolic filling anticipate diastolic heart failure and are frequently detected in patients with hypertension or diabetes. We tested the hypothesis that increased fasting and postload glucose levels are associated with diastolic dysfunction as assessed by tissue Doppler imaging (TDI) in hypertensive patients. METHODS In 104 untreated, nondiabetic, hypertensive patients free of cardiovascular complications, we measured glucose and insulin at fast and after an oral glucose load, calculated the Homeostatic Model Assessment (HOMA) index, and performed electrocardiogram (ECG), conventional echocardiography, and TDI. RESULTS Thirty-one patients who had impaired fasting glucose/impaired glucose tolerance had more frequent LV strain at ECG and worse TDI markers of diastolic function than patients with normal plasma glucose but no differences in variables LV mass, LV geometry, systolic function, and early-/late-wave transmitral diastolic velocity. TDI detected diastolic dysfunction in 46 patients who were older and had greater body mass index, blood pressure, fasting and postload glucose, insulin, HOMA index, LV mass, and left atrial diameter than patients with preserved diastolic function. Variables of diastolic function measured at TDI were significantly related with age, body mass index, LV mass, and fasting and postload plasma glucose. Stepwise regression analysis showed that the relationship of markers of diastolic dysfunction with both fasting and postload glucose levels was independent of possible confounders. CONCLUSIONS Initially abnormal fasting and postload glucose levels are associated with more prominent diastolic impairment in uncomplicated hypertensive patients, suggesting that hyperglycemia might increase the risk of diastolic heart failure even in the absence of diabetes.

Fish meal supplementation and ambulatory blood pressure in patients with hypertension: relevance of baseline membrane fatty acid composition.

BACKGROUND Studies on fish oil effects on ambulatory blood pressure (ABP) are inconclusive. We evaluated fish effects on fatty acid composition of red blood cell (RBC) membrane and ABP values and tested the hypothesis that the starting membrane fatty acid composition affects the ability to incorporate additional polyunsaturated fatty acids (PUFA) and decrease blood pressure. METHODS In 55 hypertensive patients, we measured RBC membrane fatty acid by gas chromatography and performed ABP monitoring. Patients received nutritional counseling and 3 weekly meals of trout rich in PUFA. In 42 patients, RBC membrane fatty acid and ABP were reassessed after 6 months. RESULTS At baseline, the PUFA/saturated fatty acid (SFA) ratio of RBC membrane (PUFA/SFA) was inversely related to 24-hour, daytime, and nighttime systolic and pulse pressure, a relationship that was independent of covariables. At follow-up, the PUFA/SFA ratio increased in 20 (48%) of 42 patients. Patients with increased PUFA/SFA ratio at follow-up had lower baseline PUFA/SFA ratio than patients without such increase. Fish meal supplementation decreased 24-hour systolic and diastolic pressure only in patients who had increased PUFA/SFA ratio, a change that was more prominent during the nighttime. The change in PUFA/SFA was inversely and independently related to the change in 24-hour systolic and pulse pressure, and a logistic regression analysis indicated low baseline PUFA/SFA ratio as the only independent predictor of PUFA/SFA increase and blood pressure decrease. CONCLUSIONS The ability of fish meals to increase membrane PUFA content and decrease blood pressure in hypertensive patients depends upon the starting membrane fatty acid composition.

Aldosterone and the heart: still an unresolved issue?

Receptors for mineralocorticoid hormones are expressed in myocardial cells and evidence obtained in animal studies suggests that activation of these receptors causes cardiac damage independent from blood pressure levels. In the last years, many of the issues related to the effects of aldosterone on the heart have received convincing answers and clinical investigation has focused on a variety of conditions including systolic and diastolic heart failure, arrhythmia, primary hypertension, and primary aldosteronism. Some issues, however, await clarification in order to obtain better understanding of what could be the role of aldosterone blockade in prevention and treatment of cardiovascular diseases. In this article, we overview the most recent findings of animal studies that have examined the contribution of aldosterone to cardiac function and clinical studies that have investigated the influence of aldosterone on left ventricular structure and function in the setting of primary hypertension and primary aldosteronism.

Early renal failure as a cardiovascular disease: Focus on lipoprotein(a) and prothrombotic state

Patients with renal failure are at increased risk of cardiovascular events even at the earliest stages of disease. In addition to many classic cardiovascular risk factors, many conditions that are commonly identified as emerging risk factors might contribute to occurrence of cardiovascular disease. Changes in circulating levels of many of these emerging risk factors have been demonstrated in patients with early stages of renal failure caused by different types of renal disease and have been associated with detection of cardiovascular complications. However, for most of these factors evidence of benefits of correction on cardiovascular outcome is missing. In this article, we comment on the role of lipoprotein(a) and prothrombotic factors as potential contributors to cardiovascular events in patients with early renal failure.

1C.12: DIETARY SALT INTAKE AND ALDOSTERONE-RELATED ORGAN DAMAGE IN HYPERTENSION.

Objective: Chronic exposure to elevated aldosterone levels results in cardiac and renal tissue injury with mechanisms that are independent of blood pressure levels. Although the interaction between dietary salt intake and circulating aldosterone in causing organ damage has received support in animal experiments, the evidence of this interaction in the clinical setting is much weaker. In this study we have investigated the relevance of dietary salt on aldosterone related cardiac and renal damage in primary hypertension. Design and method: In 315 untreated, grade1–2, hypertensive patients (age 47 ± 13 yr.; 173 males) we measured anthropometric variables, general biochemistries, plasma active renin and aldosterone levels, glomerular filtration rate, and 24-hour urinary sodium (UNaE) and albumin excretion (UAE), and assessed cardiac morphology and function by B-mode echocardiography. Secondary forms of hypertension were excluded by exhaustive examination in all patients. For statistical reasons, patients were subdivided into tertiles or quartiles according to their UNaE that was used as a measure of salt intake. Results: UAE increased progressively across tertiles of UNaE and patients with plasma aldosterone levels above the median of the distribution (125 pg/ml) had significantly higher UAE than patients with lower levels in all tertiles of UNaE. Search for statistical interaction between plasma aldosterone and UNaE in the association with UAE, however, did not reveal interaction. Left ventricular mass index (LVMI) was significantly greater in patients with plasma aldosterone levels above the median than patients with lower levels, but no change of LVMI was observed across quartiles of UNaE. LV geometry and ejection fraction did not differ across quartiles of UNaE and were comparable in patients with high or low plasma aldosterone levels. Both UAE and LVMI were significantly and independently related with age, body mass index, systolic blood pressure, and plasma aldosterone. UNaE was significantly related with UAE, but this relationship was lost after correction for confounders. Conclusions: In summary, circulating aldosterone contributes to subclinical renal and cardiac damage in primary hypertension, but its contribution is independent of dietary salt intake.

PREECLAMPTIC WOMEN WITH FEATURES OF SUBCLINICAL SECONDARY HYPERPARATHYROIDISM HAVE ELEVATED BLOOD PRESSURE LEVELS AFTER DELIVERY

Objective: Calcium supplementation has shown beneficial effects on blood pressure and its metabolism is altered in pregnancy hypertensive-related disorders. In this study, we hypothesized that calcium metabolism can be associated with blood pressure levels in preeclampsia complicated pregnancy. Design and method: A group of 63 multiethnic preeclamptic women (age 35 ± 6 y., 83% European, 14% African, and 3% Hispanic) was consecutively recruited at our Hypertension Unit at 1 month after delivery. We collected clinical and anthropometric variables, blood and urinary samples and performed 24-hours ambulatory blood pressure monitoring (ABPM). We measured plasma and 24-hours urinary calcium, plasma 25-hydroxycholecalciferol, parathyroid hormone (PTH), and creatinine levels, and 24-hours protein excretion. Renal function was estimated by the Modification of Diet in Renal Disease (MDRD) study equation. No women knew to be hypertensive before the current pregnancy or took calcium or vitamin D supplements. Results: At recruitment, 60% of women were taking antihypertensive agents, all of which alpha-methyldopa. For statistical purposes, we divided the group in tertiles according to PTH levels. Women in the third tertile showed biochemical characteristics of secondary hyperparathyroidism with elevated PTH and reduced vitamin D plasma levels (PTH 93 ± 15 pg/ml; 25-hydroxycholecalciferol 20 ± 8 ng/ml). In-office and ABPM blood pressure levels were higher in the third tertile then those in the first. At univariate analysis, PTH was directly associated with in-office systolic (Pearsons correlation coefficient r = 0.417; P < 0.001) and diastolic (r = 0.372; P = 0.003), 24-hours systolic (r = 0.449; P < 0.001) and diastolic (r = 0.401; P = 0.001), daytime systolic (r = 0.421; P < 0.003) and diastolic (r = 0.378; P = 0.002), and nighttime systolic (r = 0.379; P = 0.002) and diastolic (r = 0.442; P < 0.001) blood pressure. Multivariate analysis showed that PTH was associated with systolic and diastolic in-office and 24-hours blood pressure levels independently of age, body mass index, gestational week of delivery, plasma and urinary calcium, vitamin D, renal function, and urinary protein excretion. Conclusions: Plasma PTH is independently associated with blood pressure levels in the post-partum and higher blood pressure was observed in preeclamptic women with subclinical secondary hyperparathyroidism. Further evaluations on the effects of calcium and vitamin D supplementation on blood pressure control of women with a preeclamptic complication should be performed.

[PP.23.02] LOW 25-HYDROXY-VITAMIN D PLASMA LEVELS ARE ASSOCIATED WITH A MORE SEVERE FORM OF PREECLAMPSIA: A CROSS-SECTIONAL STUDY

Objective: Low levels of vitamin D have been associated with the occurrence of preeclampsia (PE) in pregnant women and, in some studies, vitamin D supplementation during pregnancy reduced the risk of PE and improved the glycometabolic profile. However, the relationship of plasma vitamin D levels with insulin-sensitivity and severity of PE has never been reported. The aim of this study was to examine the relationship between the gestational week of delivery as a marker of PE severity, the glycometabolic profile, and plasma 25-hydroxy-vitamin D (25OHVD) levels. Design and method: Sixty-nine consecutive multiethnic women with PE (35¡À6 y, 17% Africans, 80% Europeans, and 3% Hispanics) were enrolled in the study. General clinical characteristics, ambulatory blood pressure monitoring, plasma 25OHVD and parathormone (PTH) levels, glycometabolic profile, calcium metabolism, and renal function were evaluated in all women three weeks after delivery. Early onset PE was defined as delivery occurring before the 34th gestational week. Results: No women had taken 25OHVD supplementation before and during pregnancy. Prevalence of 25OHVD deficiency (<22 ng/ml) was 45%, insufficiency (<30 ng/ml) 23%, and normal levels 32%. Prevalence of early onset PE was higher in women with low 25OHVD levels than in those with normal levels (89% vs 11%; P = 0.007). Normal 25OHVD levels were observed in 40% of European women, whereas all African and Hispanic women had values below normal. 25OHVD levels were directly related with the gestational week of delivery (figure), plasma magnesium, and 24-h urinary calcium excretion, whereas its levels were inversely related with abortion number, 24-h urinary protein excretion, plasma glucose, insulin, and PTH levels, and homeostatic model assessment (HOMA) index. The relationship between HOMA index and gestational week of delivery was lost when 25OHVD was introduced in a multivariate model, but 25OHVD remained associated with gestational week of delivery independently of confounders. Conclusions: Low plasma levels of 25OHVD are independently associated with more severe PE suggesting potential benefits of 25OHVD supplementation in pregnant women at risk of PE. Figure. No caption available.

[OP.4B.05] RELATIONSHIPS BETWEEN ALCOHOL INTAKE AND LEFT VENTRICULAR DIASTOLIC FUNCTION IN HYPERTENSION: A TISSUE-DOPPLER STUDY.

Objective: Studies on heavy alcoholic drinkers have reported an association between alcohol intake and left ventricular (LV) function. The effect of moderate alcohol intake on LV function in hypertensive patients, however, is unknown. The aim of the study was to investigate the relationship between alcohol consumption and LV function in hypertension. Design and method: In 335 non-alcoholic essential hypertensive patients (age 52 ± 14 years, 177 males, 129 never treated with antihypertensive drugs) we measured anthropometric parameters, fasting plasma glucose, lipids, and liver tests, and 24-h creatinine clearance. Patients with an history of alcohol addiction (DSM IV), previous major cardiovascular events, LV ejection fraction <50%, and 24-h creatinine clearance <30 ml/min 1.72 m2 were excluded. Average daily alcohol consumption was estimated by a questionnaire (AUDIT) and patients were classified in 4 different levels (level 1 = 0 g/day, n = 172; level 2: 1–19 g/day, n = 85; level 3: 20–39 g/day, n = 55; level 4: more than 40 g/day, n = 23). LV function was assessed by both conventional echocardiography and tissue-Doppler imaging (TDI). Results: LV inner diastolic and systolic diameter, interventricular septum thickness, and LV mass index were progressively greater with increasing levels of alcohol consumption. LV ejection fraction, early/late transmitral flowrate, and isovolumic relaxation time did not differ across patients with different levels of alcohol intake, whereas left atrial diameter increased progressively with increasing alcohol intake. TDI detected LV diastolic dysfunction in 167 (49.8%) of hypertensive patients and e’ wave velocity was inversely related with alcohol consumption showing progressively impaired LV diastolic function. Patients with LV diastolic dysfunction were older, more frequently diabetics, and had higher body mass index, systolic and diastolic blood pressure, plasma glucose, cholesterol, triglycerides, GGT, and AST, and LV mass index. Multivariate logistic regression analysis of factors associated with LV diastolic dysfunction indicated that alcohol intake was a significant predictor independent of age, body mass index, blood pressure, diabetes, and LV mass index. Conclusions: In hypertensive patients without a history of alcohol addiction and normal LV systolic function, daily alcohol consumption is independently associated with LV diastolic dysfunction.

OS 20-06 DAILY ALCOHOL CONSUMPTION AFFECTS LEFT VENTRICULAR DIASTOLIC FUNCTION IN HYPERTENSION: A TISSUE-DOPPLER STUDY.

Objective: Studies on heavy alcoholic drinkers have reported an association between alcohol intake and left ventricular (LV) function. The effect of moderate alcohol intake on LV function in hypertensive patients, however, is unknown. The aim of the study was to investigate the relationship between alcohol consumption and LV function in hypertension. Design and Method: In 335 non-alcoholic hypertensive patients (age 52 ± 14) we measured plasma glucose, lipids, and liver tests, and 24-h creatinine clearance (CrCl). Patients with an history of alcohol addiction (DSM IV), previous cardiovascular events, LV ejection fraction < 50%, and CrCl < 30 ml/min1.72m2 were excluded. Average daily alcohol consumption was estimated by a questionnaire (AUDIT) and patients were classified in 4 different levels (level 1 = 0 g/day, n = 172; level 2: 1–19 g/day, n = 85; level 3: 20–39 g/day, n = 55; level 4: ≥ 40 g/day, n = 23). LV function was assessed by both conventional echocardiography and tissue-Doppler imaging (TDI). Results: LV inner dimensions, interventricular septum, and LV mass index were progressively greater with increasing levels of alcohol consumption. LV ejection fraction, early/late transmitral flowrate, and isovolumic relaxation time did not differ across patients with different levels of alcohol intake, whereas left atrial diameter increased progressively with increasing alcohol intake. TDI detected LV diastolic dysfunction in 167 (49.8%) of patients and e’ wave velocity was inversely related with alcohol consumption showing progressively impaired LV diastolic function. Patients with LV diastolic dysfunction were older, more frequently diabetics, and had higher BMI, systolic and diastolic BP, plasma glucose, cholesterol, triglycerides, &ggr;-GT, and AST, and LV mass index. Multivariate logistic regression analysis of factors associated with LV diastolic dysfunction indicated that alcohol intake was a significant predictor independent of age, BMI, BP, diabetes, and LV mass. Conclusions: In hypertensive patients without a history of alcohol addiction and normal LV systolic function, daily alcohol consumption is independently associated with LV diastolic dysfunction.