Flavia Martinis

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.

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.

[PP.22.06] PLASMA D-DIMER LEVELS ARE RELATED TO INTRARENAL VASCULAR RESISTANCE IN NON-DIABETIC ESSENTIAL HYPERTENSIVE PATIENTS

Objective: Hypertensive nephroangiosclerosis is characterized by progressive narrowing of preglomerular arterioles that leads to increased intrarenal vascular resistance. This can be estimated by duplex ultrasound evaluation and measurement of the intrarenal resistance index (IR). In addition to high blood pressure, other factors can contribute to development and progression of nephroangiosclerosis. The aim of this study was to investigate the possible relationships between some emergent cardiovascular risk factors, such as a prothrombotic state, and presence and severity of nephroangiosclerosis, as evaluated by measurement of IR, in hypertension. Design and method: In 115 non-diabetic, essential hypertensive patients (age 46 ± 13 years; 63 males, 57 never treated with anti-hypertensive drugs, 58 studied after drug wash-out of at least 2 weeks) we measured anthropometric variables, fasting plasma glucose and insulin, HOMA-index, 24-h creatinine clearance (CrCl) and urinary protein excretion, plasma levels of fibrinogen, D-dimer, prothrombin fragment 1 + 2, plasminogen activator inhibitor-1, tissue-plasminogen activator, lipoproteina (a), and homocysteine. Patients with CrCl < 30 ml/min/1.73 m2 were excluded. In all patients, IR was calculated as the average of 4 to 6 separate measurements that were obtained in the interlobar arteries respectively in the upper, middle, and lower third of both kidneys and patients were subdivided according to tertiles of IR. Results: IR was greater in women than in men, and in patients previously treated with antihypertensive drugs. Patients in the highest tertile of IR were older and had greater body mass index, pulse pressure, D-dimer and fibrinogen levels, and lower CrCl than patients in lowest IR tertile. No differences in the other variables considered in the study were found across IR tertiles. At univariate analysis IR was significantly and directly related to age, systolic and pulse pressure, HOMA-index, urinary protein excretion, D-dimer, and inversely with CrCl. At multivariate analysis, IR was independently associated with pulse pressure, CrCl and D-dimer levels. Conclusions: In non-diabetic hypertensive patients subclinical damage of intrarenal vessels is related with an activation of the hemostatic system that could play a role in the early stages of hypertensive nephropathy.

MPS 16-05 SUBCLINICAL DAMAGE OF INTRARENAL VESSELS IS ASSOCIATED WITH A PROTHROMBOTIC STATE IN NON-DIABETIC HYPERTENSIVE PATIENTS

Objective: Hypertensive nephroangiosclerosis is characterized by progressive narrowing of preglomerular arterioles that leads to increased intrarenal resistance. This can be estimated by duplex ultrasound and measurement of the intrarenal resistance index (IR). In addition to high blood pressure, other factors can contribute to nephroangiosclerosis. The aim of this study was to investigate the relationships between emergent cardiovascular risk factors and severity of nephroangiosclerosis. Design and Method: In 115 non-diabetic, essential hypertensive patients (age 46 ± 13 years; 63 males, 57 never treated with anti-hypertensive drugs, 58 studied after drug wash-out of at least 2 weeks) we measured plasma glucose and insulin, HOMA-index, 24-h creatinine clearance (CrCl) and urinary protein excretion, plasma levels of fibrinogen, D-dimer, prothrombin fragment 1 + 2, PAI-1, tPA, lipoproteina(a), and homocysteine. Patients with CrCl <30 ml/min/1.73 m2 were excluded. In all patients, IR was calculated as the average of 4–6 separate measurements that were obtained in the interlobar arteries respectively in the upper, middle, and lower third of both kidneys and patients were subdivided according to tertiles of IR. Results: IR was greater in women than in men, and in patients previously treated with antihypertensive drugs. Patients in the highest tertile of IR were older and had greater body mass index, pulse pressure, D-dimer and fibrinogen levels, and lower CrCl than patients in lowest IR tertile. No differences in the other variables considered in the study were found across IR tertiles. At univariate analysis IR was significantly and directly related to age, systolic and pulse pressure, HOMA-index, urinary protein excretion, D-dimer, and inversely with CrCl. At multivariate analysis, IR was independently associated with pulse pressure, CrCl and D-dimer levels. Conclusions: In non-diabetic hypertensive patients subclinical damage of intrarenal vessels is related with an activation of the hemostatic system that could play a role in the early stages of hypertensive nephropathy.