Gregorio Caimi

A novel component of the metabolic syndrome: The oxidative stress

The metabolic syndrome (MS) represents a cluster of cardiovascular (CV) risk factors associated to CV disease and type 2 diabetes. It is still under debate whether MS is a mere aggregation of risk factors or it represents a clinical entity with visceral obesity as underlying pathophysiological trigger. The publication of several diagnostic criteria of MS by scientific associations or experts panels reflects this uncertainty in understanding the real nature of MS. Besides the metabolic disturbances of MS, as visceral obesity, hypertriglyceridemia, low HDL cholesterol, hypertension and hyperglycemia, novel mechanisms of arterial damage have been identified. This paper reviews the evidence showing that MS and MS factors are characterized by increased oxidative stress, a relevant factor contributing to the development of metabolic and cardiovascular complications. In the next future, the measure of plasma oxidative stress may contribute to identify a subset of MS patients at increased CV risk, candidates to more intensive therapies.

Value of Home Blood Pressures as Predictor of Target Organ Damage in Mild Arterial Hypertension

Background Home blood pressure measurement has gained increasing importance for the management of hypertensive patients. The aim of our study was to compare levels of clinic (CBP), ambulatory (ABP), and home blood pressure (HBP) measurements, and their relationships with various indexes of target organ damage in I–II grade essential hypertension. Design and methods Thirty-eight essential hypertensives underwent evaluation of clinic, ambulatory and home blood pressures. Each patient recorded HBP for 2 days with a digital BP monitor three times daily, the first time on the same day during which ABP monitoring was simultaneously performed. Moreover, in all subjects electrocardiogram recording, echocardiographic study, microalbuminuria assay and fundus oculi examination were obtained. Results The average HBPs obtained on the first day, in particular systolic values, were quite similar to mean daytime ambulatory BP recorded on the same day. Clinic BP, both systolic and diastolic, showed no significant correlation with left ventricular mass index (LVMI) and with albumin excretion rate (AER), whereas a correlation barely significant was observed with an index of global target organ damage (GTODi), including cardiac, renal and retinal parameters. On the contrary, home blood pressures, especially those recorded on the second day, correlated significantly, and more tightly than clinic BP, with LVMI, AER and GTODi. Conclusions Our study seems to justify the adoption of home BP monitoring in the management of hypertensive patients, as a useful complement to clinical readings, and may provide additional prognostic information.

Effects of exercise on inflammation markers in type 2 diabetic subjects

Endothelial dysfunction and plasma markers of inflammation are significantly increased in type 2 diabetics. Several proinflammatory cytokines, acute-phase proteins, and cell adhesion molecules, such as C-reactive protein (CRP), interleukines (IL), and tumor necrosis factor alpha (TNF-α), seem to play a role in the low-grade systemic inflammation observed in these subjects. Lifestyle changes are necessary to prevent atherosclerosis and cardiovascular events. Physical exercise is known to reduce markers of inflammation by decreasing adipocytokine production and cytokine release from skeletal muscles, endothelial cells, and immune system and also improving antioxidant status. In type 2 diabetics, aerobic and resistance training have different effects on cytokine levels, and the differences in the modalities of exercise (type, duration, and intensity) and especially in the examined population could produce different results. Recent research showed that combined exercise has greater anti-inflammatory effects than aerobic or resistance exercise alone causing a deepest decrease in CRP, IL-6, IL-1β, TNF-α, leptin, and resistin and a higher increase in anti-inflammatory cytokines such as IL-4, IL-10, and adiponectin.

Role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity: a study in the Sicilian population

A proinflammatory genotype seems to contribute significantly to the risk of developing coronary heart disease (CHD). Conversely, the susceptibility alleles to inflammatory disease should be infrequent in the genetic background favoring longevity. In fact, in a modern environment, attainment of longevity is facilitated by an anti‐inflammatory status. To evaluate whether inflammatory alleles of pyrin, the gene responsible for familial Mediterranean fever (FMF) may play an opposite role in CHD and in longevity, we examined three FMF‐associated mutations, M694V (A2080G), M694I (G2082A), and V726A (T2177C), encoded by the FMF gene (MEFV) in 121 patients affected by acute myocardial infarction (AMI), in 68 centenarians, and in 196 age‐matched controls from Sicily. None of the Sicilian subjects studied carried the V726A and the M694I FMF‐related mutations. The proinflammatory M694V (A2080G) mutation was the only one we found, which was over‐represented significantly in CHD patients and under‐represented in oldest old, and intermediate values were in healthy, young controls. After adjustment for well‐recognized AMI risk factors, the M694V allele still predicted a significant risk to develop AMI. So, according to these results, we suggest that carrying the proinflammatory M694V pyrin allele may increase the risk to develop AMI. Conversely, the wild‐type pyrin genotype may predispose to a greater chance to live longer in a modern environment with reduced pathogen load and improved control of severe infections by antibiotics. All these data indicate a strong relationship among inflammation, genetics, CHD, and longevity.

Diabetes mellitus: oxidative stress and wine

SUMMARY This review focuses on the link between diabetes mellitus and oxidative stress and, in particular, on the role that moderate wine consumption may play in preventing diabetic complications and the onset of diabetes. With this aim, a search of PubMed was carried out for literature published up to March In diabetes mellitus, oxidative stress results both from exposure to hyperglycaemia through glycoxidation and sorbitol system activation, and from functional limitation of the hexose monophosphate shunt, leading to a decrease in glutathione synthesis. Oxidative stress alters the plasma lipoprotein profile (particularly low- density lipoproteins), the coagulative parameters (with an increased thrombotic risk), the endothelium (with a decrease in prostacyclin synthesis and an increase of thromboxane production) and the cell membranes (which undergo peroxidation). In diabetic patients, an altered oxidative pattern is present not only in the fasting state but also especially after food intake. In particular, food intake induces a decrease in the total radical-trapping antioxidant parameter (TRAP) and an elevation of hydroperoxides and thiobarbituric acid reactive substances (TBARS). Previously several clinical trials tried to improve the diabetic oxidative status using α-tocopherol, ascorbic acid and β-carotene supplementation. Some authors found, in normal subjects, a reduction of hydroperoxides postprandially when the meal included red wine. Other authors showed that the oxidative pattern present in type 2 diabetic patients was mitigated by red wine. These actions may reduce cardiovascular risk. Moreover, an inverse relationship was observed between alcohol consumption and the incidence of type 2 diabetes; this relationship was valid for a light to moderate intake and it seemed to depend on drinking regularly and to be independent of the type of alcoholic beverage. In conclusion, moderate and regular wine consumption could ameliorate the diabetic oxidative status. This lifestyle measure might contribute to preventing diabetic complications and the onset of diabetes.

Matrix metalloproteinases in metabolic syndrome

Metabolic syndrome is commonly accompanied by an elevated cardiovascular risk with high morbidity and mortality. The alterations of the arterial vasculature begin with endothelial dysfunction and lead to micro- and macrovascular complications. The remodeling of the endothelial basal membrane, that promotes erosion and thrombosis, has a multifactorial pathogenesis that includes leukocyte activation, increased oxidative stress and also an altered matrix metalloproteinases (MMPs) expression. MMPs are endopeptidases which degrade extracellular matrix proteins, such as collagen, gelatins, fibronectin and laminin. They can be secreted by several cells within the vascular wall, but macrophages are determinant in the atherosclerotic plaques. Their activity is regulated by tissue inhibitors of MMP (TIMPs) and also by other molecules, such as plasmin. MMPs could be implicated in plaque instability predisposing to vascular complications. It has been demonstrated that an impaired MMP or TIMP expression is associated with higher risk of all-cause mortality. A large number of studies evaluated MMPs pattern in obesity, diabetes mellitus, arterial hypertension and dyslipidemia, all of which define metabolic syndrome according to several Consensus Statement (i.e. IDF, ATP III, AHA). However, few research have been carried out on subjects with metabolic syndrome. The evidences of an improvement in MMP/TIMP ratio with diet, exercise and medical therapy should encourage further investigations with the intent to contrast the atherosclerotic process and to reduce morbidity and mortality of this kind of patients.

Low relative resting metabolic rate and body weight gain in adult Caucasian Italians

OBJECTIVE:To investigate the relationship between resting metabolic rate (RMR) and subsequent changes in body size and degree of fatness in a group of adult Caucasian Italians.DESIGN:Prospective, longitudinal, observational study.SUBJECTS:In total, 155 subjects (72 males and 83 females, age range: 18–55 y; BMI: 17.5–63.4 kg/m2) were evaluated. In total, 43 (26 m and 17 f; BMI: 28.9±1.1 kg/m2, mean±s.e.m.) of them were reassessed 10–12 y later.MEASUREMENTS:Anthropometric and body composition (bioimpedance analysis) parameters and RMR (indirect calorimetry) were taken at baseline and after 10–12 y.RESULTS:Subjects (15 m, 8 f) who gained body weight (arbitrarily defined as a change in body weight ≥5 kg) had baseline BMI (29.9±1.8 vs 28.0±1.4; P=NS) and body composition in terms of fat mass (FM%) and fat-free mass (FFM kg) comparable to those of the subjects (11 m, 9 f) whose body weight remained stable. Baseline RMR was significantly lower in subjects who gained weight than in those who did not (108±2.1 vs 122±3.1 kJ/kg-FFM 24 h; P<0.001), although it did not differ significantly between the two groups (119±2 vs 121±2 kJ/kg-FFM 24 h; P=NS) 10–12 y later. Baseline RMR was inversely correlated to both change in body weight (r=−0.57; P<0.001) and FM (r=−0.50; P<0.001).CONCLUSION:A low RMR normalized for FFM appears to be associated with body weight gain in the long run in adult Caucasian Italians.

Resting energy expenditure and body composition in morbidly obese, obese and control subjects

Resting energy expenditure (REE) was investigated by indirect calorimetry in relation to body composition and to different degrees of obesity in order to assess if a defective energy expenditure contributes to extra body fat accumulation. Differences were found between control subjects (group C; BMI 23±0.5 kg/m2, REE 5890±218 kJ/day; mean±SEM) and obese subjects (group O; BMI 34.2±0.9 kg/m2, REE 7447±360 kJ/day;P<0.0001) and between group C and morbidly obese subjects (group MO; BMI 49.9±1.6 kg/m2, REE 8330±360 kJ/day;P<0.0001); REE was not significantly different between groups O and MO. Body composition data were obtained by means of body impedance analysis. Even though group MO had a fat mass higher than group O, body cell mass, the metabolically active body compartment, was similar in groups O and MO, and this fact may have contributed to the similar REE in the two groups. Multiple regression analysis gave the following equation as the best predictor of REE: REE (kJ/day)+1591±49BW+74BCM−737G (R2=0.88), where BW is body weight, BCM is body cell mass andG is a dummy variable coding group membership (group C=1; group O=2; group MO=3). Thus the analysis showed a negative impact of obesity on REE beyond body composition variables.

Opposite role of pro-inflammatory alleles in acute myocardial infarction and longevity: results of studies performed in a Sicilian population.

Abstract:  The major trait characterizing offspring in centenarians is a reduction in the prevalence of cardiovascular disease. Because a pro‐inflammatory genotype seems to contribute significantly to the risk of coronary heart disease, alleles associated with disease susceptibility would not be included in the genetic background favoring longevity, as suggested by our previous studies on inflammatory cytokines. To confirm whether genotypes of inflammatory molecules play an opposite role in atherosclerosis and longevity, we are studying the role of other proinflammatory alleles, such as pyrin and CCR5, in acute myocardial infarction and longevity. The results support the hypothesis that the genetic background favoring cardiovascular diseases is detrimental to longevity. In addition, they suggest that the centenarian genetic background may be useful for investigating genetic key components of age‐associated diseases that are characterized by a multifactorial etiology.

Wine, Diet, and Arterial Hypertension

Hypertension is one of the leading causes of death in developed countries, and the number of prehypertensive patients is increasing. The beneficial effects of moderate wine consumption on cardiovascular diseases have been demonstrated, along with the healthy influence of a Mediterranean dietary pattern. The association of these 2 factors on hypertension and its complications is considered here. As wine polyphenols exert a vasorelaxing action, they might positively influence the hemodynamic situation of these patients. These effects could be enhanced by dietary constituents, such as garlic, onions, and olive oil, which are widely employed in Mediterranean cooking. By evaluating many studies performed in animal models and in humans, the authors conclude that moderate wine consumption, if associated with a healthy dietary pattern, such as the Mediterranean one, could help hypertensive patients to ameliorate their arterial pressure and quality of life by reducing cardiovascular morbidity and mortality rates.