Lorenzo Maroni

Neutrophils and clinical outcomes in patients with acute coronary syndromes and/or cardiac revascularisation. A systematic review on more than 34,000 subjects.

Some studies have suggested that high levels of total white blood cell (WBC) count and C-reactive protein (CRP) may be considered as independent prognostic factors in patients with acute coronary syndromes (ACS) and/or after cardiac revascularisation by percutaneous coronary intervention or coronary artery bypass grafting surgery. Evidence on the role of neutrophils in cardiovascular disease is less compelling. Therefore, we conducted a systematic review of the literature with the aim of identifying all the available evidence to clarify the role of neutrophils (absolute or relative count, neutrophil/lymphocyte ratio) as a prognostic risk factor in patients with ACS and/or cardiac revascularisation. All published studies evaluating the role of neutrophils as a risk factor for clinical outcomes were assessed using the MEDLINE and EMBASE databases. Study selection, data extraction and validity assessment was performed independently by two reviewers. Twenty-one studies (17 of which had positive results) for a total of more than 34,000 patients were included. Ten of 13 studies in ACS patients found that neutrophils measured on-admission are related to mortality rate and/or to major adverse clinical events. A predictive value of neutrophils after cardiac revascularisation procedures was reported in seven out of eight studies. Most of the studies showed that neutrophils were independent predictors of cardiovascular outcomes when analysed concomitantly with other markers of inflammation (WBC, CRP). The findings of our systematic review highlight the potential application of this inexpensive and readily available inflammatory marker for risk stratification in patients with ACS and/or cardiac revascularisation.

Use of statins and recurrence of atrial fibrillation after catheter ablation or electrical cardioversion. A systematic review and meta-analysis.

Statins have important pleiotropic effects and have been shown to reduce vascular inflammation. Some evidence suggests that statins may have a role in the primary prevention of atrial fibrillation (AF), whereas little is know on the role of statins in patients with existing AF. We performed a meta-analysis of the literature to assess the effect of statins on the recurrence of AF after electrical cardioversion or ablation. MEDLINE and EMBASE databases were searched up to January 2010. Relative risks (RR) and 95% confidence intervals (CIs) were then calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of I² statistics. Sixteen studies were included in our systematic review. Statins did not reduce the risk of AF recurrence after ablation (four studies including 750 patients; RR, 1.04; 95% CI, 0.85-1.28, p=0.71; I² = 34%). Conversely, the use of statins was associated with a significantly reduced risk of AF recurrence after electrical cardioversion (12 studies including 1790 patients; RR, 0.78; 95% CI, 0.67-0.90, p=0.0003; I² = 34%). This reduction was not statistically significant when the analysis was restricted to randomised controlled trials (RCTs) only (five studies, 458 patients, RR, 0.76; 95% CI, 0.48-1.20). In conclusion, statins may lower the risk of AF recurrence after electrical cardioversion, but not ablation. However, this finding should be considered with caution, and larger RCTs are warranted to confirm our preliminary results.

Angiotensin type 1 receptor expression and interleukin-8 production in polymorphonuclear leukocytes of patients with peripheral arterial disease.

We investigated angiotensin type 1 receptor (AT1R) expression and interleukin-8 (IL-8) productions in polymorphonuclear leukocytes obtained from patients with peripheral arterial disease (PAD) undergoing femoral endarterectomy. Subjects at high cardiovascular risk (high-risk subjects, HRS) and healthy controls (HC) were also enrolled. To this end, patients with PAD were studied 1 month before surgery, at the time of surgery, and 3 and 6 months after surgery. Polymorphonuclear leukocytes were obtained from venous blood and evaluated for AT1R expression at messenger RNA (mRNA) and protein level and IL-8 production (by means of enzyme-linked immunosorbent assay). At baseline, AT1R membrane expression was similar in cells from patients with PAD, HRS, and HC, whereas AT1R mRNA was similar in patients with PAD and HC and higher in HRS. During the follow-up period, AT1R expression progressively decreased both on the cell membrane and at the mRNA level. Both resting and stimulated production of IL-8 was lower in patients with PAD in comparison to HC and HRS and did not change during the follow up period. In PAD patients, femoral endarterectomy is associated with reduction of AT1R expression however with no apparent effect on IL-8 production. The relevance of such effects for cardiovascular protection deserves consideration.

Changes in autonomic modulation to the heart and intracellular catecholamines. A longitudinal study in differentiated thyroid carcinoma during short-term hypothyroidism and thyroid hormone replacement.

Background: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial. Methods: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2). Results: The RR interval value (p < 0.01) and systolic blood pressure (p < 0.05) were higher in phase 1 than in phase 2. The low-frequency/high-frequency (LF/HF) ratio was significantly lower in the hypothyroid state (p < 0.05), with a higher HF component (p < 0.05). After adjusting for mean RR interval in the regression model, the difference between the power of RR interval oscillations calculated in the two states was greater for the LF band (p = 0.005) and it was borderline significant for the HF band (p = 0.052). The baroreflex gain αLF index was similar in the two phases. The stimulus-induced cellular production of norepinephrine and epinephrine in peripheral blood mononuclear cells was significantly higher in phase 2. Conclusion: The neurally-mediated influences on the sinus node and the study of intracellular catecholamine production suggest a reduced sympathoexcitation in hypothyroidism compared with the treatment phase. The early increase in blood pressure observed after thyroid hormone withdrawal is not due to impaired sensitivity of the baroreflex arc.

Lipid Targets During Statin Treatment in Dyslipidemic Patients Affected by Nonalcoholic Fatty Liver Disease

Introduction:Nonalcoholic fatty liver disease (NAFLD) is associated with both dyslipidemia and increased risk for cardiovascular disease. Despite the indication to treat in patients affected by both dyslipidemia and NAFLD, an undertreatment in statin therapy due to the potential liver damage is frequently observed. We sought to evaluate retrospectively the impact of statin on the lipid profile and on the achievement of low-density lipoprotein (LDL) cholesterol targets in relation to the National Cholesterol Education Program—Adult Treatment Panel III-cardiovascular risk in dyslipidemic patients presenting with a clinical—diagnosis of NAFLD and elevated liver enzymes before statin prescription. As a secondary endpoint, the authors investigated whether statin could be associated with changes of liver enzymes. Methods:Forty-three patients with dyslipidemic NAFLD presenting with increased values of aspartate aminotransferase and/or alanine aminotransferase and/or &ggr;-glutamyl-transferase at baseline were analyzed retrospectively as regard the lipid profile and liver enzymes (values reported before statin and during statin therapy). Results:Total cholesterol, LDL and triglycerides were significantly reduced at follow-up (5.4 ± 5.4 months). The LDL target was achieved at the second visit in 30 patients (69.8%).The number of patients achieving the LDL target was significantly higher in low-risk group compared with moderate- and high-risk subjects. Liver enzyme levels showed no significant changes between baseline and follow-up. Conclusions:Statin treatment was effective (without changes in liver enzymes) in patients with dyslipidemia and NAFLD and therefore, affected by a profound alteration in lipoprotein metabolism. The number of patients achieving LDL target was related to the Adult Treatment Panel III risk classification, being higher in patients with lower risk.

Components of arterial systolic pressure and RR-interval oscillation spectra in a case of baroreflex failure, a human open-loop model of vascular control

The baroreflex control of circulation is always operating and modulates blood pressure and heart rate oscillations. Thus, the study of cardiovascular variability in humans is performed in a closed-loop model and the physiology of post-sinoaortic denervation is completely unknown in humans. We dissected for the first time the different components of systolic arterial pressure (SAP) and RR-interval spectra in a patient with ‘baroreflex failure’ (due to mixed cranial nerve neuroma) who represents a human model to investigate the cardiovascular regulation in an open-loop condition. Interactions among cardiovascular variability signals and respiratory influences were described using the multivariate parametric ARXAR model with the following findings: (1) rhythms unrelated to respiration were detected only at frequencies lower than classical low frequency (LF; Slow-LF, around 0.02 Hz) both in SAP an RR spectra, (2) small high-frequency (HF) modulation is present and related with respiration at rest and in tilt (but for SAP only) and (3) the Slow-LF fluctuations detected both in SAP and RR oscillate independently as the multivariate model shows no relationships between SAP and RR, and these oscillations are not phase related. Thus, we showed that in a patient with impaired baroreflex arc integrity the Slow-LF rhythms for RR have a central origin that dictates fluctuations on RR at the same rhythm but unrelated to the oscillation of SAP (which may be related with both peripheral activity and central rhythms). The synchronization in LF band is a hallmark of integrity of baroreflex arc whose impairment unmasks lower frequency rhythms in SAP and RR whose fluctuations oscillate independently.

Pain perception, blood pressure levels, and peripheral benzodiazepine receptors in patients followed for differentiated thyroid carcinoma: a longitudinal study in hypothyroidism and during hormone treatment.

BackgroundElevated blood pressure levels that are associated with hypalgesia and hypothyroidism have major influences on the cardiovascular system. The potential modulation of pain sensitivity by thyroid hormones is largely undetermined. Moreover, a few experimental studies show that peripheral benzodiazepine receptors (PBRs), which may be altered in hypothyroidism, seem to be related with pain perception. MethodsDental pain threshold and tolerance were evaluated in 19 patients followed for differentiated thyroid carcinoma (1) in severe short-term hypothyroidism (phase 1) and (2) during thyroid stimulating hormone-suppressive LT4 treatment (phase 2). PBR expression (cytofluorimetric evaluation) on peripheral blood mononuclear cells was also investigated in the 2 phases. ResultsPain perception differed throughout the study, the dental pain threshold was higher in phase 1 (P<0.05) whereas pain tolerance was higher but not significantly (P=0.07). Although the systolic blood pressure was higher during hypothyroidism (P<0.01), no relationship was found between blood pressure changes and pain sensitivity variations. Moreover, the multiple regression analysis showed an independent association of the clinical phase with pain sensitivity (r=−2.61, P=0.029), while accounting for systolic blood pressure. The intensity of PBRs was significantly higher in the first phase of the study (P=0.047) whereas the ratio did not significantly differ. However, no relationship was observed between pain sensitivity and PBRs. DiscussionIn conclusion, in athyreotic patients, the pain sensitivity is related to the thyroid status and is independent of the increase in blood pressure induced by thyroid hormone deprivation. The PBRs do not seem to have major influence on pain sensitivity changes in hypothyroidism.

Laminar Pattern of Mineral Calcium-Phosphorus Deposits in a Human Carotid Plaque Nanoscale Ultrastructure and Elemental Analysis

Atherosclerotic calcifications are related to poor prognosis and all-cause mortality in large population studies.1 Moreover, vascular calcifications are inversely associated with the potential reduction of plaque volume in regression studies during statin treatment, which suggests that more calcified lesions are less likely to undergo positive remodeling.2 Recently, it has been suggested that calcification is a tightly regulated process of mineralization akin to bone formation.3 In plaques, the deposits consist of a nonhomogeneous composite that contains hydroxyapatite mineral nanocrystals embedded in a collagenous organic matrix, whereas at a nanoscale level, apatite crystals interact with cholesterol crystallites. In this context, mineralization may result from a basic template pattern generated by the organic …

Lack of relationship between cardiovascular reactivity to mental stress and autonomic modulation of the sinoatrial node in normotensive and hypertensive male subjects.

A cardiovascular over-reactivity to stress may participate in the pathophysiology of hypertension. The aim of this study was to investigate whether baseline indexes of autonomic modulation of heart rate or baroreflex sensitivity were correlated with cardiovascular reactivity to stress. Spectral parameters of RR interval variability and the LF alpha-index were calculated in a resting condition in 53 untreated subjects (34 hypertensives; 19 normotensives). The reactivity to stress was expressed as changes of mean RR and systolic blood pressure during arithmetic mental stress testing. The cardiovascular reactivity was not correlated with either baseline spectral parameters of RR interval variability or LF alpha-index. In the multivariate analysis no confounding effect of diagnosis (hypertension vs normotension) was found. Moreover no interaction between diagnosis and both LF/HF ratio and LF alpha-index was observed. Thus, the cardiovascular response to a mental stimulus appears to prevail over the baseline pattern of cardiovascular regulation independently of the presence or absence of the hypertensive disease.