Francesca Nait

Elevated Homocysteine Levels Are Associated With the Metabolic Syndrome and Cardiovascular Events in Hypertensive Patients.

BACKGROUND Hyperhomocysteinemia and the metabolic syndrome are established cardiovascular risk factors and are frequently associated with hypertension. The relationship of plasma homocysteine (Hcy) with the metabolic syndrome and insulin resistance, however, is debated and studies in hypertensive patients are limited. In this study, we have investigated the association of Hcy with the metabolic syndrome and cerebro- cardiovascular events in hypertension. METHODS In 562 essential hypertensive patients who underwent accurate assessment of fasting and postload glucose metabolism, insulin sensitivity, and renal function, we measured plasma levels of Hcy, vitamin B12, folate, and fibrinogen and assessed the prevalence of the metabolic syndrome and of coronary heart and cerebrovascular disease (CVD). RESULTS Patients with the metabolic syndrome had significantly higher plasma Hcy levels. After correction for covariates, increasing Hcy levels were associated with an increasing prevalence of the metabolic syndrome, coronary heart disease, and CVD. Plasma Hcy was directly correlated with age, waist circumference, fasting glucose, triglyceride, uric acid, and fibrinogen levels, and homeostatic model assessment index and inversely with creatinine clearance and high-density lipoprotein cholesterol, vitamin B12, and folate levels. Logistic regression analysis showed an independent association of Hcy levels with age, male gender, vitamin B12 and folate levels, and the metabolic syndrome. Logistic regression indicated also an independent association of Hcy with cerebro-cardiovascular disease that was independent of the metabolic syndrome. CONCLUSIONS Elevated plasma Hcy is associated with the metabolic syndrome in hypertensive patients. Prevalence of events increases with increasing plasma Hcy levels suggesting a contribution of Hcy to cerebro-cardiovascular diseases in these patients.

Subclinical carotid artery disease and plasma homocysteine levels in patients with hypertension

Information on the association between homocysteine (Hcy) levels and subclinical carotid artery disease is limited. We investigated the relationship of plasma Hcy concentration with carotid artery plaques and intima-media thickness (IMT) in patients with hypertension. In 486 essential hypertensive patients who underwent ultrasound examination of the carotid arteries, we measured plasma levels of Hcy, vitamin B12, folate, and C-reactive protein. Plaques were detected in 34% of the study patients. Plasma Hcy levels were significantly greater in hypertensive patients with evidence of carotid plaques than patients without carotid plaques. Carotid IMT progressively increased across quartiles of plasma Hcy levels. Multivariate regression showed that carotid IMT was independently related with age, blood pressure, C-reactive protein, and Hcy levels. In a logistic regression, age, blood pressure, triglyceride, and Hcy independently predicted the presence of carotid plaques. Thus, elevated plasma Hcy levels are associated with asymptomatic carotid disease in hypertensive patients suggesting a role of Hcy in the development and progression of carotid atherosclerosis in these patients.

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.

THE ARTERIAL STIFFNESS IS INFLUENCED BY THE HEMOSTATIC SYSTEM IN NON-DIABETIC HYPERTENSIVE PATIENTS

Objective: In the general population an increased arterial stiffness is associated with a high risk of cardiovascular events. In essential hypertension high plasma fibrinogen and D-dimer levels are associated with cardiovascular damage. The aim of this study was to search for a relationship between indexes of activation of the coagulation system and parameters of arterial stiffness, such as the pulse wave velocity (PWV) and the augmentation index (AIx), in essential hypertensive patients without diabetes or renal failure. Design and method: In 76 hypertensive patients (age 52 ± 14 y; 35 male; 30 never treated with antihypertensive drugs) we evaluated clinical and anthropometric variables, plasma level of glucose, lipids, fibrinogen and D-dimer, and creatinine clearance, PWV e AIx. Results: Patients were subdivided into tertiles of PWV. Patients with higher PWV were older, more frequently males, had a greater percentage of antihypertensive drugs, a greater alcohol consumption, and higher fibrinogen e D-dimer levels than in patients with lower PWV. At univariate analysis the PWV was significantly and directly related to age, BMI, systolic pressure, duration of hypertension, alcohol intake, plasma levels of glucose, fibrinogen (r = 0.369, P = 0.001) and D-dimer (r = 0.390, P < 0.001). The PWV was higher in males than females (P = 0.036) and in previously treated patients than in naive subjects (P = 0.003). At multivariate analysis including PWV as the dependent variable, PWV was independently associated with age (beta = 0.310, P = 0.015) and D-dimer levels (beta = 0.222, P = 0.049). At univariate analysis AIx was significantly and directly related to age, total and LDL-cholesterol, fibrinogen (r = 0.349, P = 0.002), and inversely related to diastolic pressure, and it was higher in previous treated than in never treated patients. At multivariate analysis AIx was independently associated with age (beta = 0.235, P = 0.048) and LDL-cholesterol (beta = 0.328, P = 0.003). Conclusions: This study supports the hypothesis of an association of a prothrombotic state with the vascular damage of hypertension that might contribute to the cardiovascular risk in these patients.

[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.

[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.

Plasma lipoprotein(a) levels and atherosclerotic renal artery stenosis in hypertensive patients.

Background/Aims: The contribution of emergent cardiovascular risk factors to atherosclerotic renal artery stenosis (ARAS) is debated. We investigated the relationship of lipoprotein(a) and prothrombotic factors with ARAS in hypertension. Methods: In 50 hypertensive patients with angiographic evidence of ARAS and 58 hypertensive patients who had comparable cardiovascular risk factor burden but no evidence of renovascular disease, we measured renal function, lipoprotein(a), homocysteine, and hemostatic-fibrinolytic markers. Results: Patients with ARAS were more frequently smokers and had longer duration of hypertension, heavier antihypertensive treatment, and worse renal function than controls. Lipoprotein(a) was higher in patients with ARAS than controls, whereas no differences were found in homocysteine and all hemostatic variables. Multivariate analysis showed that lipoprotein(a) was associated with ARAS independent of other confounders including renal function and history of coronary heart, cerebrovascular, and peripheral artery disease. Conclusion: Lipoprotein(a) might contribute to the development of ARAS and detection of elevated levels of this lipoprotein could raise the suspicion of renovascular disease in patients with high blood pressure.