Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design,methods and initial experience

The Isfahan Healthy Heart Programme (IHHP) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases (CVD) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population. IHHP started late in 1999 and will be finished in 2005-2006. A primary survey was done to collect baseline data from interventional (Isfahan and Najaf-Abad) and reference (Arak) communities. In a two-stage sampling method, we randomly selected 5 to 10 percent of households from randomly selected clusters. Then individuals aged > or = 19 years were selected for the survey. This way, data from 12,600 individuals (6300 in interventional counties and 6300 in the reference county) was collected and stratified according to living area (urban vs. rural) and different age and sex groups. The samples underwent a 30-minute interview to complete validated questionnaires containing questions on demography, socioeconomic status, smoking behaviour, physical activity, nutritional habits and other behaviour regarding CVD. Blood pressure and body mass index (BMI) measurements were done and fasting blood samples were taken for two hours post load plasma glucose (2 hpp), serum (total, HDL and LDL) cholesterol and triglyceride levels. A twelve-lead electrocardiogram was recorded in all persons above 35 years of age. Community-wide surveillance of deaths, hospital discharges, myocardial infarction and stroke registry was carried out in the intervention and control areas. Four to five years of interventions based on different categories such as mass media, community partnerships, health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention. Considering the results of the baseline surveys, (assessments needed, the objectives, existing resources and the possibility of national implementation) the interventions were planned. They were set based on specific target groups like school children, women, work-site, health personnel, high-risk persons, and community leaders were actively engaged as decision makers. A series of teams was arranged for planning and implementation of the intervention strategies. Monitoring will be done on small samples to assess the effect of different interventions in the intervention area. While four periodic surveys will be conducted on independent samples to assess health behaviours related to CVD risk factors in the intervention and reference areas, the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death, fatal and nonfatal MI and stroke. The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study.     

Degradation and Characterisation of Electrospun Polycaprolactone (PCL) and Poly(lactic-co-glycolic acid) (PLGA) Scaffolds for Vascular Tissue Engineering

The current study aimed to evaluate the characteristics and the effects of degradation on the structural properties of Poly(lactic-co-glycolic acid) (PLGA)- and polycaprolactone (PCL)-based nanofibrous scaffolds. Six scaffolds were prepared by electrospinning, three with PCL 15% (w/v) and three with PLGA 10% (w/v), with electrospinning processing times of 30, 60 and 90 min. Both types of scaffolds displayed more robust mechanical properties with increased spinning times. The tensile strength of both scaffolds with 90-min electrospun membranes did not show a significant difference in their strengths, as the PCL and PLGA scaffolds measured at 1.492 MPa ± 0.378 SD and 1.764 MPa ± 0.7982 SD, respectively. All membranes were shown to be hydrophobic under a wettability test. A degradation behaviour study was performed by immersing all scaffolds in phosphate-buffered saline (PBS) solution at room temperature for 12 weeks and for 4 weeks at 37 °C. The effects of degradation were monitored by taking each sample out of the PBS solution every week, and the structural changes were investigated under a scanning electron microscope (SEM). The PCL and PLGA scaffolds showed excellent fibre structure with adequate degradation, and the fibre diameter, measured over time, showed slight increase in size. Therefore, as an example of fibre water intake and progressive degradation, the scaffold’s percentage weight loss increased each week, further supporting the porous membrane’s degradability. The pore size and the porosity percentage of all scaffolds decreased substantially over the degradation period. The conclusion drawn from this experiment is that PCL and PLGA hold great promise for tissue engineering and regenerative medicine applications.     

Subendocardial stress in pre‐eclampsia

A primigravida 26‐year‐old woman who had developed pre‐eclampsia with malignant hypertension at 30 weeks of gestation suffered acute myocardial infarction two days postpartum. Electrocardiogram demonstrated diffuse ST‐segment depression suggestive of subendocardial ischemia. Echocardiography demonstrated focal asymmetric left ventricular hypertrophy, with a characteristic “basal septal bulge”, and a left ventricular mid‐cavitary gradient of 51 mmHg. Coronary angiography revealed normal coronary arteries and vascular flow. Peripartum acute myocardial infarction is rare and portends a high mortality. However, to date, only one case of acute myocardial infarction associated with asymmetric left ventricular hypertrophy and pre‐eclampsia has been described in the literature.     

Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome

The functional relevance of brain-derived neurotrophic factor (BDNF) is beginning to be well appreciated not only in mice, but also in humans. Because reduced levels typically correlate with impaired neuronal function, increasing BDNF levels with well-tolerated drugs diffusing into the central nervous system may help in ameliorating functional deficits. With this objective in mind, we used the sphingosine-1 phosphate receptor agonist fingolimod, a drug that crosses the blood-brain barrier. In addition, fingolimod has recently been introduced as the first oral treatment for multiple sclerosis. In cultured neurons, fingolimod increases BDNF levels and counteracts NMDA-induced neuronal death in a BDNF-dependent manner. Ongoing synaptic activity and MAPK signaling is required for fingolimod-induced BDNF increase, a pathway that can also be activated in vivo by systemic fingolimod administration. Mice lacking Mecp2, a gene frequently mutated in Rett syndrome, show decreased levels of BDNF, and fingolimod administration was found to partially rescue these levels as well as the size of the striatum, a volumetric sensor of BDNF signaling in rodents. These changes correlate with increased locomotor activity of the Mecp2-deficient animals, suggesting that fingolimod may improve the functional output of the nervous system, in addition to its well-documented effects on lymphocyte egress from lymph nodes.     

Cytomegalovirus Localization in Atherosclerotic Plaques is Associated with Acute Coronary Syndromes: Report of 105 Patients

It has been shown that cytomegalovirus (CMV) is present in coronary atherosclerotic plaques, but the clinical rele-vance of this presence remains to be elucidated. In this study we sought to examine CMV infection in atherosclerosis patients defined by different methods and to identify the clinical significance of CMV replication in the atherosclerotic plaques. The study included 105 consecutive patients who were admitted to our department and underwent coronary artery bypass grafting (CABG) surgical interventions. Coronary atherosclerotic specimens as well as 53 specimens from the mamillary artery of these same patients were analyzed. Enzyme-linked immunosorbent assay (ELISA) and poly-merase chain reaction (PCR) methods were used for evaluations. The CMV PCR test result was positive for 28 (26.7%) of patients with coronary artery atherosclerosis. After adjusting for other risk factors, coronary artery disease patients with a history of acute coronary syndrome were more likely to be positive for CMV PCR test (P=0.027; odds ratio: 4.2; 95% CI: 1.18-15.0). They were also more likely to have a positive family history for cardiovascular diseases (CVD). This study confirms previous evidence about the replication of CMV virus in the atherosclerotic plaques of coronary arteries and brings clinical significance to this observation by showing a higher prevalence of acute coronary syndromes in those patients with CMV-infected plaques. Our study also suggests a familial vulnerability to CMV replication in the coronary artery walls.     

Traumatic Coronary Artery Fistula Closure with Stent Graft

We present a rare case of a symptomatic acquired large coronary fistula and aneurysm secondary to chest trauma that was successfully closed using stent graft. This case is followed by review of the literature.     

Contrast-enhanced intravascular ultrasound: combining morphology with activity-based assessment of plaque vulnerability

Acute coronary syndromes are the result of coronary plaque rupture in the majority of cases. Available diagnostic techniques that focus on the early detection of plaques that are prone to rupture are still limited. Increased neovascularization in the vasa vasorum of the atherosclerotic plaque has been identified recently as a common feature of inflammation and plaque vulnerability. Microbubbles, which have been used for ultrasound imaging, can be used to trace neovascularization. We present recent advances in contrast agents and contrast-enhanced intravascular ultrasound that may be used for the detection of vasa vasorum, including fundamental and harmonic contrast imaging. Identification of vasa vasorum proliferation in atherosclerotic plaques presents important clinical implications; in particular it could provide a means to detect vulnerability in vivo, thereby guiding targeted treatments.     

Intrinsic Frequency and the Single Wave Biopsy: Implications for Insulin Resistance

Insulin resistance is the hallmark of classical type II diabetes. In addition, insulin resistance plays a central role in metabolic syndrome, which astonishingly affects 1 out of 3 adults in North America. The insulin resistance state can precede the manifestation of diabetes and hypertension by years. Insulin resistance is correlated with a low-grade inflammatory condition, thought to be induced by obesity as well as other conditions. Currently, the methods to measure and monitor insulin resistance, such as the homeostatic model assessment and the euglycemic insulin clamp, can be impractical, expensive, and invasive. Abundant evidence exists that relates increased pulse pressure, pulse wave velocity (PWV), and vascular dysfunction with insulin resistance. We introduce a potential method of assessing insulin resistance that relies on a novel signal-processing algorithm, the intrinsic frequency method (IFM). The method requires a single pulse pressure wave, thus the term “ wave biopsy.”