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Maurizio Cesari

Publications and source records attributed to Maurizio Cesari.

13 recordsLinked to original sources
PubMed2006

The T(-786)C endothelial nitric oxide synthase genotype predicts cardiovascular mortality in high-risk patients.

OBJECTIVES: This study sought to investigate the impact of a common T(-786)C single-nucleotide polymorphism (SNP) in the promoter of the endothelial nitric oxide synthase (eNOS, NOS3) gene on cardiovascular (CV) death in a prospective cohort study. BACKGROUND: The T(-786)C SNP eNOS gene implies a blunted endothelium-dependent vasodilation in hypertensive patients and was associated with multivessel coronary artery disease in cross-sectional studies, but it remained unsettled whether it carried prognostic information. METHODS: In consecutive white patients of the GENICA (Genetic and Environmental Factors in Coronary Atherosclerosis) study, who underwent coronary angiography between 1999 and 2001, we determined the incidence of CV death at follow-up. The eNOS T(-786)C and the exon 7 G(894)T SNPs were determined by melting curve analysis of amplicons from allele-specific fluorescence resonance energy transfer probes. Plasma levels of nitrate/nitrite, nitrotyrosine, and myeloperoxidase were also measured. The Kaplan-Meier and Cox regression analyses were used to assess the impact of SNPs on event-free survival. RESULTS: Complete follow-up data were obtained in 1,086 (98%) patients. After a median follow-up of 1,296 days (range 4 to 2,057 days), we observed 85 (8.2%) CV deaths. There was a significant impact of the T(-786)C eNOS genotype on CV death-free (p = 0.0102) survival, but no differences in CV death rates across G(894)T genotypes. The TT individuals, who showed a lower survival, exhibited higher plasma myeloperoxidase (p < 0.0001) and lower levels of nitrotyrosine (p < 0.0001) than CC patients. CONCLUSIONS: The T(-786)C SNP in the promoter of eNOS bears independent prognostic information and is associated with changes in markers of oxidant stress in high-risk white patients referred for coronary angiography.

Aged↗
PubMed2006

Hyperhomocysteinemia predicts total and cardiovascular mortality in high-risk women.

OBJECTIVE: The impact of homocysteine on cardiovascular disease can be more detrimental in women than in men, but it is unknown whether this applies to high-risk women. We therefore investigated the association of hyperhomocysteinemia with coronary artery disease (CAD) and cardiovascular mortality in high-risk women referred for CAD, both in the total population and in the hypertensive and normotensive cohorts. DESIGN: A prospective study cohort. SETTING: A tertiary centre. PATIENTS INCLUSION CRITERIA: 262 consecutive Caucasian postmenopausal women referred for coronary angiography. EXCLUSION CRITERIA: acute myocardial infarction and vitamin supplementation. MAIN OUTCOME MEASURE(S): We assessed total plasma homocysteine (tHcy), folate levels, and the MTHFR677C-->T polymorphism. CAD was defined as a modified Duke Index score greater than 0; hyperhomocysteinemia as tHcy levels of 15 micromol/l or greater. The primary study outcome was cardiovascular mortality at follow-up. RESULTS: Mild/moderate and severe hyperhomocysteinemia was found in 15.1 and 1.6% of women, respectively, without differences between CAD and non-CAD women. By the ATPIII criteria, 92.2% of the women were in the highest risk class and 55% had CAD; however, no association of tHcy with the CAD score was found. After a median follow-up of 3.6 years, 23 women (9.1%) had died, 15 (6%) of cardiovascular causes. Women with high tHcy levels showed the worst all-cause and cardiovascular death-free survival at Kaplan-Meier and Cox regression analysis. Moreover, in the hypertensive cohort only women with hyperhomocysteinemia showed increased cardiovascular mortality. CONCLUSION: Hyperhomocysteinemia is common in high-risk women and adversely affects their prognosis, although it is unrelated to the CAD atherosclerotic burden.

Aged↗
PubMed2005

Is homocysteine important as risk factor for coronary heart disease?

AIM: Homocysteine (Hcy), a sulfur-containing amino acid product of methionine metabolism, may play an important role in the development of cardiovascular disease. In this paper we review available knowledge on the pathways leading to synthesis and degradation of Hcy, as well as on the genetic and environmental factors affecting its plasma levels, focussing on its potential role in the development of coronary heart disease. DATA SYNTHESIS: Hyperhomocysteinemia (HHcy) is determined by genetic and environmental factors and represents a modifiable cardiovascular risk factor since vitamin supplementation has been shown to effectively lower plasma homocysteine levels. While case-control and cross-sectional studies consistently showed an association of HHcy with cardiovascular disease, prospective studies have given conflicting results. Thus, the role of HHcy in the development of coronary heart disease is still under debate. Furthermore, it remains unclear which patients should be screened for HHcy and treated to correct HHcy. CONCLUSIONS: Available information collectively suggests that although HHcy can be regarded as a minor risk factor for coronary heart disease, it interacts with other risk factors in triggering new events in patients with known CAD. Thus, the treatment of mild HHcy with folate supplementation is appropriate in particular in high risk patients or patients with established CAD who do not present with the "traditional" risk factors.

Aging↗
PubMed2004

Hyperhomocysteinemia is inversely related with left ventricular ejection fraction and predicts cardiovascular mortality in high-risk coronary artery disease hypertensives.

OBJECTIVE: The purpose of this study was to investigate the relationship of plasma homocysteine (tHcy) levels with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) in high-risk patients undergoing coronary angiography for suspected CAD. METHODS AND RESULTS: In 936 consecutive patients, we measured LVEF, tHcy, folate levels, and quantified CAD with a modified Duke Index score. We also genotyped patients at the methylen-tetrahydrofolate-reductase 677C-->T polymorphism. Hyperhomocysteinemia (HHcy) was defined as tHcy levels > or =15.46 micromol/L; total and cardiovascular mortality was assessed at follow-up that lasted 43 months (median). CAD was confirmed in 75% of patients and ruled out in the rest (non-CAD group). No relationship of HHcy with either arterial hypertension or the CAD score was found. In contrast, there was a significant inverse relationship of tHcy with LVEF in arterial hypertensive but not in normotensive patients, regardless of previous myocardial infarction. At logistic regression, HHcy was the strongest predictor (P=0.001) of a low (<40%) LVEF, followed by type 2 diabetes mellitus and cigarette smoking. At follow-up, HHcy significantly predicted cardiovascular mortality but only in the arterial hypertension subgroup. CONCLUSIONS: In arterial hypertensive but not in normotensive patients, HHcy predicts cardiovascular mortality and a low LVEF, independent of CAD and history of myocardial infarction.

Coronary Artery Disease↗
PubMed2004

Combined antihypertensive and lipid-lowering treatment.

Hypertension and hypercholesterolemia are frequently associated, and their treatment is proven to reduce cardiovascular risk. Current guidelines on cardiovascular prevention strongly recommend treating both disorders. Unfortunately, the low treatment and control rates, combined with the high prevalence of both conditions, still contribute to the high burden of cardiovascular disease in Western countries. In the past 5 years, many studies evaluating the benefit of combined antihypertensive and lipid-lowering treatment on endothelial dysfunction, coronary atherosclerosis, hypertension control, and on primary and secondary prevention of cardiovascular events have been published. In this article, we discuss and critically evaluate the available evidence on the potential benefits of combined antihypertensive and lipid-lowering treatment.

Anticholesteremic Agents↗
PubMed2003

Antibodies to oxidized low-density lipoproteins and angiographically assessed coronary artery disease in white patients.

BACKGROUND: Low-density lipoprotein (LDL) can be oxidatively modified by reactive oxygen species, thus generating oxLDL. The latter induce formation of specific antibodies (oxLDLAb), which are detectable in patients with atherosclerosis, in which they might play a pathogenic or a protective role. Thus, we aimed to investigate the association of antibodies with oxidized LDLs (oxLDL) (oxLDLAbs) with coronary artery disease (CAD) and acute coronary syndromes. METHODS AND RESULTS: In a cross-sectional study of 529 consecutive patients undergoing quantitative coronary angiography for suspected CAD, we measured the titer of IgG oxLDLAbs by ELISA. With regression analysis techniques, we also investigated the determinants of oxLDLAb titer and the association of oxLDLAbs with CAD severity. We found no significant differences of oxLDLAb titer between groups of patients without and with different CAD severity. The oxLDLAb titer was 18.6 enzyme units (EU) (11.5 to 25.7 EU/mL) (mean, 95% CI) in patients without CAD; 16.8 EU (9.6 to 24.2 EU) in patients with stenosis <50%; and 19.9 EU (15 to 24.8 EU), 17.2 (13.8 to 20.6 EU), and 14.7 EU (12.1 to 17.3 EU) in those with in 1-, 2-, or 3-vessel > or =50% stenosis, respectively. Similarly, no differences of oxLDLAb titer between patients without and with acute coronary syndrome were found. The oxLDLAb titer correlated weakly with aging and with serum total, LDL, and HDL cholesterol and plasma homocysteine levels; however, only age and HDL cholesterol remained significant predictors of the oxLDLAb titer at a stepwise regression analysis. CONCLUSIONS: The results of this study, which was adequately powered from the statistical standpoint, provided no evidence for an association of IgG oxLDLAb titer with angiographically assessed CAD in whites.

Age Factors↗
PubMed2003

The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study.

OBJECTIVES: We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD). BACKGROUND: Endothelial dysfunction foretells cardiovascular events and can be genetically determined. METHODS: We genotyped for the promoter (T(-786)C) and exon 7 (Glu298Asp, G(894)T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5'- and 3'-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T(-786)C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD. RESULTS: The overall genotype distribution of T(-786)C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T(-786)C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T(-786)C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041). CONCLUSIONS: The C allele at the T(-786)C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.

Adult↗
PubMed2003

Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension.

BACKGROUND: Endothelin (ET)-1 contributes to raising blood pressure (BP) and inducing cardiovascular disease by vasoconstriction and potent stimulation of aldosterone secretion. In the rat this latter effect occurs via ET(B) receptors; in humans in vitro studies implicated both ET(A) and ET(B) receptors, but there is no conclusive evidence in vivo. METHODS: We recruited 13 consenting hypertensive patients: six with primary aldosteronism (PA) and seven with high-to-normal renin hypertension (HNRH). They were infused with a low dose (200 nmol/min for 5 min followed by 100 nmol/min for 10 min) of the ET(A)-selective antagonist BQ-123 either alone or, on a different day, together with an identical dose of the ET(B)-selective antagonist BQ-788. Plasma aldosterone, cortisol and ACTH concentration and plasma renin activity (PRA) were measured with radioimmunoassay at -15, 0, 30, 60, 120, 240, 360 min, while BP was recorded non-invasively. RESULTS: BQ-123 alone and combined with BQ-788 significantly lowered mean BP in both PA and HNRH patients (by 6-10 mmHg at nadir; P<0.01). In PA patients, a short-lived decrease of aldosterone was elicited by combined BQ-123 and BQ-788 (-14%; P<0.05), but not by BQ-123 alone; cortisol, ACTH, and PRA were unaffected by either treatment. In HNRH patients, BQ-123 both alone and combined with BQ-788 lowered aldosterone (-39 and -28%, respectively) and PRA (-43 and -16%, respectively), while cortisol and ACTH were unaffected. CONCLUSIONS: Endogenous ET-1 contributes to maintaining the high BP values and the aldosterone secretion in both PA and HNRH patients. In the former patients, the aldosterone secretagogue effect of ET-1 is mediated via ET(B) receptors, while in the latter it occurs mainly via ET(A)-mediated stimulation of renin production.

Adrenocorticotropic Hormone↗
PubMed2003

Under treatment with lipid-lowering drugs of high-risk coronary heart disease patients of the GENICA study.

OBJECTIVES: To assess the proportion of high-risk coronary artery disease (CAD) patients who received lipid lowering drug treatment (LLDT) and met the LDL-Cholesterol (LDL-C) goal of 100 mg/dl defined by the third report of the U.S. National Cholesterol Education Program (NCEP). METHODS: In 86% (n = 1095) of the 1268 consecutive Italian patients, who were enrolled in the GENICA study after undergoing quantitative coronary angiography for suspected coronary artery disease between 1999 and 2001, the levels of total serum cholesterol, HDL-cholesterol, triglycerides, and LDL-C were measured and accurate information on current LLDT were available. All patients were classified according to the NCEP. RESULTS: Seventy-four percent of the patients (n = 805) had established CAD and cardiovascular events and therefore were candidates for secondary prevention with LLDT; 69% of them had concomitant hyperlipidemia. Only 57% of the patients with CAD and hyperlipidemia were on LLDT. Of the 1052 patients who were at the highest risk class according to NCEP, only 34.2% and 16.7% were on LLDT and reached the LDL-C goal, respectively. CONCLUSIONS: Only 1 patient of 6 in the highest-risk class according to the NCEP accomplished the LDL-C goal. Accordingly, in the field of secondary prevention of coronary artery disease, the implementation of guidelines that emerged from scientific evidence into clinical practice with LLDT still requires major efforts.

Aged↗
PubMed2002

Biological properties of the angiotensin peptides other than angiotensin II: implications for hypertension and cardiovascular diseases.

Several peptides of the RAS other than angiotensin (1-8) have been identified. They are generally referred as 'angiotensin fragments': Ang (2-8), Ang (3-8) and Ang (1-7) and have been detected in human tissues. There is evidence that they may play a functional role in humans by acting in concert with angiotensin (1-8) and aldosterone. Available knowledge on the pathways leading to synthesis and degradation of angiotensin fragments, as well as on their interactions with receptors and on their possible role in cardiovascular homeostasis and disease are reviewed.

Angiotensins↗
PubMed2002

Renal vein renin measurements accurately identify renovascular hypertension caused by total occlusion of the renal artery.

OBJECTIVE: To assess the usefulness of indexes derived from renal vein renin measurements. DESIGN: A 12-year prospective study. SETTING: A tertiary institutional referral centre. PATIENTS AND METHODS: Between 1988 and 2000, we studied 152 consecutive hypertensive patients with a high pre-test probability of renovascular hypertension (RVH). RVH was diagnosed retrospectively on the basis of reduction in blood pressure after correction of ischaemia at follow-up. Renal vein renin measurements were used to calculate the ratios: Visch/Vctl (renal vein renin ratio; RVRR); Vctl/Viivc; (Visch - Viivc)/Viivc; (Vctl - Viivc)/Viivc, where Visch and Vctl indicate plasma renin activity (PRA) in the ischaemic and contralateral renal veins, respectively, and Viivc denotes PRA in the infrarenal inferior vena cava. A receiver operator characteristics (ROC) curve analysis was used to determine the cut-off value of renal vein renin measurement indexes that provided the best discrimination between patients with and without RVH and to identify patients with RVH caused by total occlusion of the renal artery. RESULTS: Sixty-seven patients were diagnosed as having RVH: 51 had significant renal artery stenoses (RVH non-occluded) and 16 had total renal artery occlusion (RVH occluded). Of the remaining 85 patients in whom RVH was excluded (non-RVH group), 27 had reno-parenchymal hypertension and 58 had essential hypertension. Of the renal vein renin measurement indexes, only RVRR and (Visch - Viivc)/Viivc in RVH-occluded patients differed significantly (P < 0.005) from those in the non-RVH group and showed the best performance by ROC curve analysis. This analysis also showed that, at any cut-off value, RVRR was far more accurate for identification of RVH-occluded patients than for identification of RVH non-occluded patients, both in the subgroup with unilateral and, even more so, in those with bilateral renal artery lesions. The best trade-off between sensitivity and false-positive rate was provided by cut-off values of 1.55 and 1.70 of the RVRR for identification of non-occluded and occluded RVH, respectively. CONCLUSIONS: RVRR is more useful for establishing an indication for nephrectomy in patients with renal artery occlusion than for identifying those patients with renal artery stenosis who will benefit from revascularization. In patients with RVH with bilateral renal artery lesions, lateralization of renin secretion occurs only in the presence of total renal artery occlusion. Different cut-off values are necessary for identification of non-occluded and occluded RVH.

Adolescent↗
PubMed2002

Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism.

Hyperaldosteronism has been causally linked to myocardial interstitial fibrosis experimentally, but it remains unclear if this link also applies to humans. Thus, we investigated the effects of excess aldosterone due to primary aldosteronism (PA) on collagen deposition in the heart. We used echocardiography to estimate left ventricular (LV) wall thickness and dimensions and for videodensitometric analysis of myocardial texture in 17 consecutive patients with PA and 10 patients with primary (essential) hypertension who were matched for demographics, casual blood pressure, and known duration of hypertension. The groups differed in serum K+, ECG PQ interval duration, plasma renin activity, and aldosterone levels (all P< or =0.002) but not for casual blood pressure values, demographics, and duration of hypertension. Compared with hypertensive patients, PA patients showed a higher LV mass index (53.7+/-1.8 versus 45.5+/-2.0 g/m(2.7); P=0.008) and lower values of the cyclic variation index of the myocardial mean gray level of septum (CVI(s); -12.02+/-5.84% versus 6.06+/-3.08%; P=0.012) and posterior wall (-11.13+/-6.42% versus 8.63+/-9.62%; P=0.012). A regression analysis showed that CVI(s) was predicted by the PQ duration, supine plasma renin activity, plasma aldosterone, and age, which collectively accounted for approximately 36% of CVI(s) variance. PA is associated with alterations of myocardial textures that suggest increased collagen deposition and that can explain both the dependence of LV diastolic filling from presystole and the prolongation of the PQ interval.

Adult↗