Mohammad Madjid

Cardiovascular risk factors in an Iranian urban population: Tehran Lipid and Glucose Study (Phase 1)

Summary.Objectives: Coronary artery disease is becoming more prevalent in developing countries, particularly in urban areas. This study was conducted to determine the prevalence of cardiovascular risk factors among Tehran urban population. Methods: The prevalence and distribution of high blood pressure, cigarette smoking, dyslipoproteinemia, diabetes mellitus, and obesity was determined in 15005 subjects, aged three years and over, selected by cluster random sampling in Tehran urban district-13 between February 1999 to August 2001. Total energy intake, percent of energy derived from protein, carbohydrate, and fat were assessed in a subsidiary of 1474 persons by means of two 24-hour dietary recalls. Results: In adults, 78% of men and 80% of women presented at least one CVD risk factor. The percentage of adult women with two or more risk factors was significantly greater than the one for men. Prevalence of DM, hypertension, obesity, high TC, low HDL, high TGs, and smoking was 9.8, 20.4, 14.4, 19.3, 32, 5.3, and 22.3%, respectively. In children and adolescents, two or more CVD risk factors were found in 9% of boys and 7% of girls. Prevalence of hypertension, obesity, high TC, low HDL, and high TGs, was 12.7, 5.2, 5.1, 10.2, and 5%, respectively. The mean percentage values of energy intake derived from carbohydrate, protein, and fat were 57.8±6.9, 11.1±1.8, and 30.9±7.2, respectively. Conclusion: The prevalence of cardiovascular risk factors among Tehran urban population is high; particularly of high total cholesterol, low HDL cholesterol levels, and high waist to hip ratio. An effective strategy for life style modification is a cornerstone of a population approach to the cardiovascular risk factors. Moreover, these results will serve as a baseline for assessment of future trends in the risk factors studied.

Role of acute infection in triggering acute coronary syndromes

Acute coronary syndromes are a leading cause of morbidity and mortality worldwide. The mechanisms underlying the triggering of these events are diverse and include increased coronary and systemic inflammatory activity, dominant prothrombotic conditions, increased biomechanical stress on coronary arteries, variations in the coronary arterial tone, disturbed haemodynamic homoeostasis, and altered myocardial metabolic balance. There is experimental evidence that acute infections can promote the development of acute coronary syndromes, and clinical data strongly support a role for acute infections in triggering these events. In our Review, we summarise the pathogenesis of coronary artery disease and present the evidence linking acute infections with the development of acute coronary syndromes. Greater awareness of this association is likely to encourage research into ways of protecting patients who are at high risk.

Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein E-deficient mice

Background—The role of infection in the development and complications of atherosclerosis has been the focus of much attention. We reported previously that influenza vaccination was associated with reduced risk of recurrent myocardial infarction. Here, we report the effect of influenza A virus on the apolipoprotein E–deficient (apoE−/−) mouse, an animal model of atherosclerosis. Methods and Results—Twenty-four apoE−/− mice >24 months old were injected with 1 LD50 (lethal dose 50) of influenza A virus. Ten wild-type C57BL/6 infected mice and 11 noninfected age-matched apoE−/− mice served as controls. Multiple aortic sections were studied histologically 3, 5, and 10 days later. The infected mice showed markedly increased intimal cellularity compared with the noninfected apoE−/− mice. No aortic abnormalities were seen in infected wild-type mice. Ten infected apoE−/− mice had a significant subendothelial infiltrate composed of a heterogeneous group of cells that stained positively for smooth muscle cell actin, F4/80 (macrophages), and CD3 (T lymphocytes). One case of subocclusive platelet and fibrin-rich thrombus was seen. Conclusions—This study shows that influenza infection promotes inflammation, smooth muscle cell proliferation, and fibrin deposition in atherosclerotic plaques.

Influenza and cardiovascular disease: a new opportunity for prevention and the need for further studies.

In the United States, 12 400 000 people live with a history of heart attack, angina pectoris, or both. Of this population, an estimated 1 100 000 will suffer a new or recurrent coronary attack this year.1 According to the World Health Organization, cardiovascular disease (CVD) will be the leading cause of death worldwide by 2020.2 Infectious agents have been implicated in the etiology of atherosclerosis and its complications since the early 1900s.3 Clinicians have long noticed that ≈30% of myocardial infarctions (MIs) are preceded by an upper respiratory infection.4,5 Agents implicated in atherosclerosis include cytomegalovirus (CMV), Chlamydia pneumoniae , Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), Helicobacter pylori , Mycoplasma pneumoniae , Porphyromonas gingivalis , and Enterovirus.6–13 Antibiotic therapy for C. pneumoniae in CVD patients has been tried with transient or no benefit to date.14,15 Ongoing studies may give a definitive answer by late 2003.16 Here, we review recent studies suggesting influenza may play a role in atherogenesis or atherothrombosis. In 2000, we reported a case-control study in patients with known coronary artery disease; influenza vaccination was associated with a 67% reduction (OR 0.33, 95% CI 0.13 to 0.82, P =0.017) in risk of MI in the subsequent influenza season.17 In a simultaneous population-based case-control study, Siscovick et al18 found that after adjusting for demographic, clinical, and behavioral risk factors, influenza vaccination was associated with a 49% reduction (OR 0.51, 95% CI 0.33 to 0.79) in risk of out-of-hospital primary cardiac arrest. Another case-control study reported a 50% risk reduction (OR 0.50, 95% CI 0.26 to 0.94, P =0.033) in stroke risk in subjects vaccinated during the year of the study and a 48% (OR 0.42, 95% CI 0.21 to 0.81, P =0.009) risk reduction in those vaccinated …

Influenza epidemics and acute respiratory disease activity are associated with a surge in autopsy-confirmed coronary heart disease death: results from 8 years of autopsies in 34 892 subjects

Abstract Aims To determine whether influenza can trigger heart attacks, we investigated the impact of influenza epidemics on autopsy-proven coronary deaths. Methods and results We studied weekly death due to acute myocardial infarction (AMI) and chronic ischaemic heart disease (IHD) in autopsies conducted in 1993 to 2000 in St Petersburg, Russia. We plotted the weekly acute respiratory disease (ARD) counts and influenza epidemics against AMI and chronic IHD deaths. There were 11 892 subjects dying of AMI and 23 000 subjects dying of chronic IHD. Median age was 75 for women and 65 for men. In every year, a peak of AMI and chronic IHD deaths were present and coincided with the influenza epidemic and peak ARD activity. A similar pattern was seen for each subgroup of men, women, subjects 50 years or older, and subjects 70 years or older. When comparing the average influenza epidemic weeks to average off-season weeks, the odds for AMI and chronic IHD death increased by 1.30 (95% confidence interval (CI): 1.08–1.56) and 1.10 (95% CI: 0.97–1.26), respectively. Conclusion Influenza epidemics are associated with a rise in autopsy-confirmed coronary deaths. Influenza vaccination should be advocated for patients at high risk of developing cardiovascular events.

Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir

Influenza epidemics cause numerous deaths and millions of hospitalizations each year. Because of the alarming emergence of resistance to anti-influenza drugs, there is a need to identify new naturally occurring antiviral molecules. We tested the hypothesis that pomegranate polyphenol extract (PPE) has anti-influenza properties. Using real time PCR, plaque assay, and TCID 50% hemagglutination assay, we have shown that PPE suppresses replication of influenza A virus in MDCK cells. PPE inhibits agglutination of chicken red blood cells (cRBC) by influenza virus and is virucidal. The single-cycle growth conditions indicated that independent of the virucidal effect PPE also inhibits viral RNA replication. PPE did not alter virus ribonucleoprotein (RNP) entry into nucleus or translocation of virus RNP from nucleus to cytoplasm in MDCK cells. We evaluated four major Polyphenols in PPE (ellagic acid, caffeic acid, luteolin, and punicalagin) and demonstrated that punicalagin is the effective, anti-influenza component of PPE. Punicalagin blocked replication of the virus RNA, inhibited agglutination of chicken RBCs by the virus and had virucidal effects. Furthermore, the combination of PPE and oseltamivir synergistically increased the anti-influenza effect of oseltamivir. In conclusion, PPE inhibited the replication of human influenza A/Hong Kong (H3N2) in vitro. Pomegranate extracts should be further studied for therapeutic and prophylactic potential especially for influenza epidemics and pandemics.

pH Heterogeneity of human and rabbit atherosclerotic plaques; a new insight into detection of vulnerable plaque

BACKGROUND Atherosclerotic plaques are heterogeneous with respect to inflammation, calcification, vascularity, oxygen, and temperature. We hypothesized that they also vary in pH and measured pH in living human carotid endarterectomized atherosclerotic plaques (CEA), Watanabe heritable hyperlipidemic (WHHL) rabbit aortas and human umbilical arteries (HUA). METHODS AND RESULTS We measured pH of CEA of 48 patients, nine WHHL rabbit aortas and 11 HUA specimens (as controls) using a glass type microelectrode mounted on a micromanipulator in a 37 degrees C incubator. We also used single emission and also dual emission fluorescence ratio imaging microscopy employing pH-sensitive probes to confirm pH heterogeneity. Mean pH measured at 415 points of CEA was 7.55+/-0.32; at 275 points of WHHL rabbit aortas it was 7.40+/-0.43; and in 233 points of HUA it was 7.24+/-0.1. In CEA, pH of yellow (lipid-rich) areas was significantly lower than pH in calcified areas (7.15+/-0.01 vs. 7.73+/-0.01, P<0.0001). The coefficients of variation (heterogeneity) of pH in CEA, WHHL rabbit aortas, and HUA were 0.038+/-0.010, 0.039+/-0.007, and 0.009+/-0.003, respectively (P=0.0001). Fluorescence microscopic imaging confirmed pH heterogeneity in both humans and rabbits but not in HUA. In a variance components analysis 82% of the heterogeneity was due to the within-plaque variation and 2% was attributable to between-plaque variation. CONCLUSIONS Our findings support the hypothesis of pH heterogeneity in plaques, and suggest a possible role for detecting low pH in the detection of plaque vulnerability. The source of pH heterogeneity particularly acidic pH, its impact on the stability of plaques and its potential clinical utility in locating vulnerable plaques remain to be evaluated.

Superparamagnetic Iron Oxide–Based Method for Quantifying Recruitment of Monocytes to Mouse Atherosclerotic Lesions In Vivo Enhancement by Tissue Necrosis Factor-α, Interleukin-1β, and Interferon-γ

Background—It has been found recently that the MRI contrast agent superparamagnetic iron oxide (SPIO) localizes to aortic atherosclerotic plaques. We therefore asked whether SPIO might be used to monitor monocyte recruitment into aortic atherosclerotic plaques. Methods and Results—Eleven female apo E knockout (K/O) mice, each 11 months old, were divided into 2 groups. Six mice received tissue necrosis factor-&agr; (0.2 &mgr;g IP once), interleukin-1&bgr; (0.2 &mgr;g IP once), and interferon-&ggr; (100 U/g per day IP for 5 days); 5 received 0.5 mL saline containing1% BSA and served as sham-treated atherosclerotic controls. Two wild-type C57BL/6 mice served as sham-treated nonatherosclerotic controls. Three hours after initial cytokine or sham treatment, all mice received SPIO by intravenous injection (1 mmol/kg iron). Six days later, all mice were euthanized, the hearts and aortas were perfused under physiological pressure, and the entire aortas were studied histologically. Atherosclerotic plaques in cytokine-treated mice contained more iron-positive macrophages per cross section than did those in sham-treated apo E K/O control mice (42±11.8 versus 11.6±5.9) (P <0.0001). Iron-laden macrophages were present either in subendothelial plaque surfaces or in thin layers overlying the internal elastic lamina, often at the edges of atherosclerotic plaques. No iron deposition was seen in aortas of the wild-type nonatherosclerotic control mice. Immunocytochemistry showed mostly macrophages and few T lymphocytes in atherosclerotic plaques of cytokine-treated mice. Conclusions—SPIO allows detection of iron-laden macrophages in the aortic subendothelium of apo E–deficient mice under basal conditions and monitoring of monocyte recruitment after cytokine injection.

The role of periadventitial fat in atherosclerosis.

CONTEXT It has become increasingly evident that adipose tissue is a multifunctional organ that produces and secretes multiple paracrine and endocrine factors. Research into obesity, insulin resistance, and diabetes has identified a proinflammatory state associated with obesity. Substantial differences between subcutaneous and omental fat have been noted, including the fact that omental fat produces relatively more inflammatory cytokines. Periadventitial fat, as a specific adipose tissue subset, has been overlooked in the field of atherosclerosis despite its potential diagnostic and therapeutic implications. OBJECTIVE To review (1) evidence for the role of adventitial and periadventitial fat in vessel remodeling after injury, (2) the relationship between adventitial inflammation and atherosclerosis, (3) the association between periadventitial fat and plaque inflammation, and (4) the diagnostic and therapeutic implications of these roles and relationships for the progression of atherosclerosis. DATA SOURCES We present new data showing greater uptake of iron, administered in the form of superparamagnetic iron oxide, in the periadventitial fat of atherosclerotic mice than in control mice. In addition, macrophage density in the periadventitial fat of lipid-rich plaques is increased compared with fibrocalcific plaques. CONCLUSIONS There is a striking paucity of data on the relationship between the periadventitial fat of coronary arteries and atherosclerosis. Greater insight into this relationship might be instrumental in making strides into the pathophysiology, diagnosis, and treatment of coronary artery disease.

Acute Bacterial Pneumonia is Associated With the Occurrence of Acute Coronary Syndromes

A link between acute infections and the development of acute coronary syndromes (ACS) has been proposed. We used retrospective cohort and self-controlled case series analyses to define the closeness of the association between acute bacterial pneumonia due to Streptococcus pneumoniae or Haemophilus influenzae and ACS. For the retrospective cohort analysis we included a control group of patients with admission diagnoses other than pneumonia or ACS. For the self-controlled case series analysis, we made within-person comparisons of the risk for ACS during the 15 days after admission for pneumonia with that of 365 days before and after that event. In 206 pneumonia patients (144 S. pneumoniae, 62 H. influenzae) we identified 22 (10.7%) cases of ACS, which compared to 6 (1.5%) among 395 controls resulted in an odds ratio (OR) of 7.8 (95% confidence interval [CI], 3.1-19.4). With multivariate logistic regression analysis, the OR for ACS in the pneumonia group remained elevated (OR, 8.5; 95% CI, 3.4-22.2). By the self-controlled case series method, the risk of ACS remarkably increased during the first 15 days after the diagnosis of pneumonia (incidence rate ratio, 47.6; 95% CI, 24.5-92.5). The characteristics and strength of these associations suggest a causal role for the acute infection in this relationship. Abbreviations: ACS = acute coronary syndromes, CI = confidence interval, ICU = intensive care unit, IRR = incidence rate ratio, OR = odds ratio.