Francesco Natale

Visceral adiposity and arterial stiffness: echocardiographic epicardial fat thickness reflects, better than waist circumference, carotid arterial stiffness in a large population of hypertensives

AIMS Relationship between obesity and cardiovascular (CV) disease depends not only on the amount of body fat, but also on its distribution. For example, individuals with increased fat accumulation in the abdominal region have atherogenic lipid profiles and are at increased CV risk. The loss of elasticity in medium and large arteries is an early manifestation of atherosclerosis. The aim of this study was to evaluate whether echocardiographic epicardial adipose tissue, an index of cardiac adiposity, is related to carotid stiffness and carotid intima-media thickness (IMT), indexes of subclinical atherosclerosis, better than waist circumference in hypertensive patients. METHODS AND RESULTS We studied 459 patients with Grade I and II essential hypertension who were referred to our outpatient clinic over a period from May 2007 to March 2008. The population was first sorted by waist circumference and then by epicardial fat < or = 7 or >7 mm. We measured epicardial fat thickness, waist circumference, carotid artery stiffness, and carotid IMT in all patients. Patients divided according to waist circumference showed no statistical differences in carotid artery stiffness between the two groups. Subjects with epicardial fat >7 mm were older, had higher systolic, diastolic, and pulse pressure, increased left ventricular mass index, carotid IMT, diastolic parameters, and stiffness parameters compared with those with epicardial fat < or = 7 mm (P < 0.001). A positive correlation was found between epicardial fat and age, pulse pressure, stiffness parameters, carotid IMT, systolic blood pressure, and duration of hypertension, and a negative correlation was found with diastolic parameters. Age, carotid IMT, and stiffness parameters were independently related to epicardial fat. CONCLUSION Our findings indicate that epicardial fat reflects carotid artery stiffness in hypertension-induced organ damage.

Inflammation and Cardiovascular Disease: From Pathogenesis to Therapeutic Target

Atherosclerosis represents the most common pathological substrate of coronary heart disease (CHD), and the characterization of the disease as a chronic low-grade inflammatory condition is now largely accepted. A number of mediators of inflammation have been widely studied, both as surrogate biomarkers and as causal agents, in the pathophysiological network of atherogenesis and plaque vulnerability. The epidemiological observation that biomarkers of inflammation are associated with clinical cardiovascular risk supports the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk on the background of traditional medical therapy. A large number of randomized controlled trials have shown that drugs commonly used in cardiovascular disease (CVD), such as statins, may be effective in the primary and secondary prevention of cardiovascular events through an anti-inflammatory effect. Moreover, several anti-inflammatory drugs are being tested for their potential to reduce residual cardiovascular risk on the background of validated medical therapy for atherosclerotic disease. In this paper, we review relevant evidence with regard to the relationship between inflammation and CVD, from pathogenesis to therapeutic strategies.

Effects of coexisting hypertension and type II diabetes mellitus on arterial stiffness

Hypertension (HT) is frequently associated with diabetes mellitus (DM) and its prevalence doubles in diabetics compared to the general population. This high prevalence is associated with increased stiffness of large arteries, which often precedes macrovascular events. The aim of our study was to evaluate the influence of HT and type II DM on aortic stiffness in patients with one disease or the other compared to those with both HT and type II DM. We studied 220 patients, 50 with type II DM (Group A), 50 with HT (Group B), 85 with both diseases (Group C), and 35 healthy subjects (HS). Regional arterial stiffness was assessed by automatic measurement of the carotid–femoral pulse wave velocity (PWV). For each patient, we evaluated: age, sex, body mass index, smoking habit, heart rate, SBP/DBP, pulse pressure (PP), mean BP, fasting glucose, lipid profile, uric acid, and fibrinogen. Group C had significantly more women and non smokers and the highest PP (61±14 mmHg). Of biochemical parameters, only fibrinogen was higher in Group A and in Group C (P<0.01 and P<0.001, respectively). Group C had a significantly higher PWV than the other four groups (P<0.0001). Stepwise forward regression analysis showed that fasting glucose was the first independent determinant of PWV (P<0.0001). In conclusion, this study shows that patients with DM and HT have higher arterial stiffness compared to HS and those with one disease or the other. Fasting glucose is the major independent determinant of PWV, which may be used as a relevant tool to assess the influence of cardiovascular risk factors on arterial stiffness in high-risk patients.

Renal resistive index and cardiovascular organ damage in a large population of hypertensive patients

We evaluated the relationship between renal resistive index (RRI) of the intrarenal vasculature and cardiovascular (CV) organ damage such as left ventricular hypertrophy (LVH), diastolic dysfunction and carotid atherosclerosis in a large sample of hypertensive patients. 566 hypertensive patients underwent echocardiography with conventional Doppler and Doppler tissue imaging (DTI), carotid and renal ultrasonography. In addition, lipids profile, creatinine in serum, and urinary albumin concentrations were determined. The patients were divided according to their RRI values in 2 groups: <70 and ⩾70. Subjects with high RRI were older, had higher systolic and pulse pressure (PP) and more years of hypertension, compared to those with low RRI (P<0.0001). Patients with the higher RRI showed an increased left ventricular mass index (LVMI) and carotid intima–media thickness (IMT) with a higher prevalence of LVH, carotid plaques and microalbuminuria (P<0.001). There were differences in overall diastolic parameters, in particular when evaluated by DTI (P<0.001). A positive correlation was found between RRI and age, PP, carotid IMT, LVMI, SBP and a negative correlation was found with DTI diastolic parameters (P<0.001). Age, PP, carotid IMT and LVMI were independently related to RRI. While, RRI was independently related to IMT and IVRT. RRI, especially the higher values, are positively correlated with target organ damage in hypertensive patients, indicating that renal vascular resistance is related to morphologic and hemodynamic alteration of the CV system. The evaluation of RRI could predict the presence of early CV damage and provide an accurate estimate of overall risk.

Arterial distensibility and ambulatory blood pressure monitoring in young patients with neurofibromatosis type 1

Vascular disease is an underestimated complication of neurofibromatosis type 1 (NF1). The few studies available on this disease are based on case reports. The purpose of this study was to evaluate the relationship between 24-h systolic blood pressure (SBP) and 24-h heart rate obtained by ambulatory blood pressure monitoring and the carotid femoral pulse wave velocity, a widely used index of arterial distensibility, evaluated with Complior. We studied 64 young NF1 patients and 30 healthy subjects. There was no difference in pulse wave velocity between NF1 patients and healthy subjects. Ten of the NF1 patients showed 24-h SBP or 24-h diastolic blood pressure (DBP) >95th percentile for age and sex. We divided the NF1 group into subgroups: NF1 patients with 24-h SBP and 24-h DBP < or = 95th percentile for age and sex (NF1A group) and NF1 patients with mean SBP or DBP >95th percentile for age and sex (NF1B group). The pulse wave velocity of NF1A and NF1B patients were 6.3 +/- 1 m/sec and 6.4 +/- 1 m/sec, respectively (P = not significant). A significant relationship was found between 24-h SBP, 24-h heart rate, and pulse wave velocity in healthy subjects, but not in all NF1 patients and also between the NF1A and NF1B groups. Distensibility of the central arteries may be altered by various environmental or genetic factors. Thus, genetic determinants may play a role in the response of the large arteries to blood pressure. The recent discovery of neurofibromin in aortic smooth muscle may explain the vascular abnormalities present in NF1 patients. We emphasize the importance of a careful vascular evaluation using a noninvasive method, such as Complior and a periodic ambulatory blood pressure monitoring to detect NF1 patients at high risk of vascular complications.

Effects of Monotherapy and Combination Therapy on Blood Pressure Control and Target Organ Damage: A Randomized Prospective Intervention Study in a Large Population of Hypertensive Patients

This prospective, randomized trial evaluated the effect of monotherapy and different combination therapies on cardiovascular target organ damage and metabolic profile in 520 hypertensive patients. Patients were allocated to a single agent: carvedilol 25 mg, amlodipine 10 mg, enalapril 20 mg, or losartan 50 mg (groups C, A, E, and L, respectively). After 2 months (level 2), nonresponders received a low‐dose thiazide diuretic, and after 4 months (level 3), amlodipine (groups E, C, and L) and carvedilol (group A). Twenty‐four‐hour blood pressure was significantly lowered in all treatment groups. Blood pressure control was more pronounced in patients receiving two or three drugs. At the end of the study, the carotid intima‐media thickness decreased in group L (P<.01), left ventricular mass index in groups E and L (P<.05 and P<.001, respectively), with a concomitant reduction in cholesterol in group L (P<.03). Diastolic function improved significantly in group L (P<.05). This study describes the need to control blood pressure with two or more drugs in most hypertensive patients and illustrates good clinical outcomes, independent of blood pressure lowering, using combination therapy with losartan, low‐dose thiazide, and amlodipine.

Educational level and hypertension: how socioeconomic differences condition health care

This is the first European study that has evaluated educational level in a large sample of hypertensive outpatients. We established the educational level of the hypertensive outpatients in our unit, and determined whether the awareness of hypertension and its organ damage was education-related. We analysed data from 812 consecutive outpatients (378 men, mean age 50 ± 10 years) with essential stage I–II hypertension. Subjects were subdivided into two categories: group A subjects were highly educated; group B subjects had a little education. Data were compared with educational level from the 1991 population census for the Campania region (ISTAT data) and with 200 type 2 diabetes patients (96 men, mean age 51 ± 9 years) from the nearest diabetes unit. For each hypertensive patient we considered clinical, echocardiographic and biochemical parameters. Data from the last census showed a high percentage (80%) of subjects with low education. The percentage of type 2 diabetic patients with little education was high (190 patients, 95%). Conversely, it is somewhat surprising that most hypertensive patients reached high standards of education and worked at sedentary jobs (group A: 736 patients, 91%; P < 0.0001). Multivariate analysis showed that only diastolic blood pressure (P = 0.03) was independently associated with low educational level. Compared to diabetes, hypertension and its risk factors are relatively unknown to people with little education. Education is associated with greater health care and awareness that may overcome the risk related to low physical activity. Thus, we stress the importance of a sound health policy able to reach out to the uneducated and make them aware of hypertension and the health care services available to them.

Adipose tissue and vascular inflammation in coronary artery disease.

Obesity has become an important public health issue in Western and developing countries, with well known metabolic and cardiovascular complications. In the last decades, evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences. As a consequence of the expansion of fat depots, in obese subjects, adipose tissue cells develope a phenotypic modification, which turns into a change of the secretory output. Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling, vascular biology and, moreover, participate to the systemic inflammatory response, which characterizes obesity and metabolic syndrome. This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events. A great number of adipocytokines have been described recently, linking inflammatory mileu and vascular pathology. The understanding of these pathways is crucial not only from a pathophysiological point of view, but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets. The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease.

Does the angiotensin II receptor antagonist losartan improve cognitive function

Newer classes of antihypertensive agents, such as angiotensin II receptor antagonists, may offer benefits to patients in addition to their ability to lower blood pressure. It is accepted that chronic hypertension contributes to the development of cerebrovascular and cardiovascular disease, and several studies have demonstrated a link between hypertension and reduced cognitive function, especially in patients not receiving antihypertensive medication. In an initial clinical trial, the angiotensin II receptor antagonist losartan was shown to improve cognitive function in patients with hypertension, including in those who were elderly (up to 73 years of age). This effect cannot be explained by a reduction in blood pressure alone and is likely to involve interactions with the diverse biological actions of the renin-angiotensin system.Improving or maintaining cognitive function in patients with hypertension may translate into economic benefits beyond those expected due to blood pressure control, and would result in considerable quality-of-life benefits for the aging population.

The impact of the ketogenic diet on arterial morphology and endothelial function in children and young adults with epilepsy: A case–control study

PURPOSE The present study aimed to assess the impact of the ketogenic diet on arterial morphology and endothelial function of the big vessels of the neck and on cardiac diastolic function, in a cohort of epileptic children and young adults treated with the ketogenic diet. METHODS Patients were recruited based on the following inclusion criteria: (1) patients who were or had been on the ketogenic diet for a time period of at least six months. Each patient underwent measurement of carotid intima media thickness, carotid artery stiffness, echocardiography, and diastolic function assessment. Patients with drug resistant epilepsy, matched for number, age and sex and never treated with ketogenic diet, were recruited as controls. RESULTS The population study was composed by 43 epilepsy patients (23 males), aged between 19 months and 31 years (mean 11 years). Twenty-three patients were or had been treated with ketogenic diet, and 20 had never been on it (control group). Subjects treated with the ketogenic diet had higher arterial stiffness parameters, including AIx and β-index and higher serum levels of cholesterol or triglycerides compared to those who had never been on the diet (control group) (p<0.001). CONCLUSIONS Arterial stiffness is increased in children and young adults treated with the ketogenic diet, before the increase of the intima media thickness. This supports that arterial stiffness is an early marker of vascular damage.