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.

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.

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.

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.

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.