Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency.

Deficiency of cystathionine beta-synthase (CBS) is a genetic disorder of transsulfuration resulting in elevated plasma homocyst(e)ine and methionine and decreased cysteine. Affected patients have multisystem involvement, which may include light skin and hair. Reversible hypopigmentation in treated homocystinuric patients has been infrequently reported, and the mechanism is undefined. Two CBS-deficient homocystinuric patients manifested darkening of their hypopigmented hair following treatment that decreased plasma homocyst(e)ine. We hypothesized that homocyst(e)ine inhibits tyrosinase, the major pigment enzyme. The activity of tyrosinase extracted from pigmented human melanoma cells (MNT-1) that were grown in the presence of homocysteine was reduced in comparison to that extracted from cells grown without homocysteine. Copper sulfate restored homocyst(e)ine-inhibited tyrosinase activity when added to the culture cell media at a proportion of 1.25 mol of copper sulfate per 1 mol of DL-homocysteine. Holo-tyrosinase activity was inhibited by adding DL-homocysteine to the assay reaction mixture, and the addition of copper sulfate to the reaction mixture prevented this inhibition. Other tested compounds, L-cystine and betaine did not affect tyrosinase activity. Our data suggest that reversible hypopigmentation in homocystinuria is the result of tyrosinase inhibition by homocyst(e)ine and that the probable mechanism of this inhibition is the interaction of homocyst(e)ine with copper at the active site of tyrosinase.     

Physical activity and stroke in British middle aged men.

OBJECTIVES--To assess the relation between physical activity and stroke and to determine the overall benefit of physical activity for all major cardiovascular events. DESIGN--Prospective study of a cohort of men followed up for 9.5 years. SETTING--General practices in 24 towns in England, Wales, and Scotland (British regional heart study). SUBJECTS--7735 men aged 40-59 at screening, selected at random from one general practice in each of 24 towns. MAIN OUTCOME MEASURES--Fatal and non-fatal strokes and heart attacks. RESULTS--128 major strokes (fatal and non-fatal) occurred. Physical activity was inversely associated with risk of stroke independent of coronary risk factors, heavy drinking, and pre-existing ischaemic heart disease or stroke (relative risk 1.0 for inactivity, 0.6 moderate activity, and 0.3 vigorous activity; test for trend p = 0.008). The association remained after excluding men reporting regular sporting (vigorous) activity. However, vigorous physical activity was associated with a marginally significant increased risk of heart attack compared with moderate or moderately vigorous activity in men with no pre-existing ischaemic heart disease or stroke (relative risk 1.6%; 95% confidence interval 0.96 to 2.8). In men with symptomatic ischaemic heart disease or stroke those doing moderately vigorous or vigorous activity had a risk of heart attack slightly higher than that in inactive men (relative risk = 1.6; 0.8 to 3.3). CONCLUSIONS--Moderate physical activity significantly reduces the risk of stroke and heart attacks in men both with and without pre-existing ischaemic heart disease. More vigorous activity did not confer any further protection. Moderate activity, such as frequent walking and recreational activity or weekly sporting activity, should be encouraged without restriction.     

Risk factors for stroke in middle aged British men.

OBJECTIVE--To determine the risk factors for stroke in a cohort representative of middle aged British men. DESIGN--Prospective study of a cohort of men followed up for eight years. SETTING--General practices in 24 towns in England, Wales, and Scotland (the British regional heart study). SUBJECTS--7735 men aged 40-59 at screening, selected at random from one general practice in each town. MAIN OUTCOME MEASURE--Fatal and non-fatal strokes. RESULTS--110 of the men had at least one stroke; there were four times as many non-fatal as fatal strokes. The relative risk of stroke was 12.1 in men who had high blood pressure (systolic blood pressure greater than or equal to 160 mm Hg) and were current smokers compared with normotensive, non-smoking men. Diastolic blood pressure yielded no additional information, and former cigarette smokers had the same risk as men who had never smoked. Heavy alcohol intake was associated with a relative risk of stroke of 3.8 in men without previously diagnosed cardiovascular disease. Men with pre-existing ischaemic heart disease had an increased risk of stroke, but only when left ventricular hypertrophy on electrocardiography was also present. CONCLUSIONS--Systolic blood pressure, cigarette smoking, and left ventricular hypertrophy on electrocardiography in men with pre-existing ischaemic heart disease were found to be the major risk factors for stroke in middle aged British men. Heavy alcohol intake seemed to increase the risk of stroke in men without previously diagnosed cardiovascular disease. A large proportion of strokes should be preventable by controlling blood pressure and stopping smoking.     

Bezafibrate in men with lower extremity arterial disease: randomised controlled trial

ObjectiveTo assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease.DesignDouble blind placebo controlled randomised trial.Setting85 general practices and nine hospital vascular clinics.Participants1568 men, mean age 68.2 years (range 35 to 92) at recruitment.InterventionsBezafibrate 400 mg daily (783 men) or placebo (785 men).ResultsBezafibrate did not reduce the incidence of coronary heart disease and stroke. There were 150 and 160 events in the active and placebo groups respectively (relative risk 0.96, 95% confidence interval 0.76 to 1.21). There were 90 and 111 major coronary events in the active and placebo groups respectively (0.81, 0.60 to 1.08), of which 64 and 65 were fatal (0.95, 0.66 to 1.37) and 26 and 46 non-fatal (0.60, 0.36 to 0.99). Beneficial effects on non-fatal events were greatest in men aged <65 years at entry, in whom benefit was also seen for all coronary events (0.38, 0.20 to 0.72). There were no significant effects in older men. There were 60 strokes in those on active treatment and 49 in those on placebo (1.34, 0.80 to 2.01). There were 204 and 195 deaths from all causes in the two groups respectively (1.03, 0.83 to 1.26). Bezafibrate reduced the severity of intermittent claudication for up to three years.ConclusionsBezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events, particularly in those aged <65 years at entry, in whom all coronary events may also be reduced.

What is already known on this topic

The beneficial effects of bezafibrate on blood lipids and fibrinogen concentrations should reduce the incidence of heart attacks and strokesSo far, however, there is only limited evidence on clinical outcomes from randomised controlled trials

What this study adds

Treatment with bezafibrate was not associated with a reduction in the combined incidence of heart attacks and strokes, though there were substantially fewer non-fatal heart attacks in those taking bezafibrateBezafibrate was associated with a reduction in the incidence of all heart attacks, especially non-fatal, in men aged <65 yearsBezafibrate seems to reduce the severity of intermittent claudication for two or three years     

Fish Consumption,Mercury Intake,and the Associated Risks to the Kuwaiti Population

This analysis uses recent data on fish consumption among Kuwaitis and on levels of Hg in fish collected from fish markets in Kuwait to estimate the human health risks to the Kuwaiti population due to consumption of fish containing Hg. Mercury is a known human neurotoxicant. Recent, somewhat controversial, evidence suggests that it also may play a role in cardiovascular disease. Our analysis indicates that roughly 5,000 IQ points are lost among the 30,000 Kuwaiti infants born each year and that approximately 15 fatal heart attacks each year among middle-aged and elderly Kuwaitis may be attributed to consumption of methyl Hg in fish. Approximate 90% confidence intervals are from 1,800 to 14,000 IQ points lost annually and from 0 to 72 fatal heart attacks each year. The confidence intervals for neurotoxicity are broad because of uncertainty about the slope of the dose–response and the existence of a threshold. The range of estimates for heart attacks includes zero because of residual uncertainty about the causality of observed associations between methyl Hg exposure and cardiovascular disease. These results do not imply that Kuwaitis should immediately reduce their consumption of fish, but do suggest that a careful risk–risk tradeoff analysis may be warranted.     

Predisposing factors for cerebral infarction: the Oxfordshire community stroke project.

The frequency of known causative factors of cerebral infarction was studied in 244 cases of first ever stroke due to cerebral infarction proved by computed tomography or at necropsy who were registered in the first two years of a prospective community based study. Risk factors for cerebral infarction were present in 196 (80%) cases; hypertension in 126 (52%); ischaemic heart disease in 92 (38%); peripheral vascular disease in 60 (25%); a cardiac lesion that was a major potential source of embolism to the brain in 50 (20%); transient ischaemic attacks in 35 (14%); cervical arterial bruit in 33 (14%); and diabetes mellitus in 24 (10%). Thirty one patients (13%) were in atrial fibrillation. Of the 48 patients who were free of risk factors or a major potential cardiac source of embolism at the time of the stroke, 18 were found to have hypertension after the stroke and 10 to have non-atheromatous non-embolic conditions (migrainous cerebral infarction (three), arteritis (two), inflammatory bowel disease (one), arterial trauma (one), autoimmune disease (one), carcinoma of the thyroid (one), and major operation (one). In 20 patients no causative factors could be identified. In this unselected series of patients with first ever stroke due to cerebral infarction most of the strokes were presumed to be due to either atheromatous arterial disease or embolism from the heart, and only 4% (95% confidence interval 2 to 7%) were probably due to non-atheromatous non-embolic causes. This has implications for research into strokes and allocation of public health expenditure.     

Cardiovascular alterations and autonomic imbalance in an experimental model of depression

Depressed patients with and without a history of cardiovascular pathology display signs, such as elevated heart rate, decreased heart rate variability, and increased physiological reactivity to environmental stressors, which may indicate a predisposition to cardiovascular disease. The specific physiological mechanisms associating depression with such altered cardiovascular parameters are presently unclear. The current study investigated cardiovascular regulation in the chronic mild stress rodent model of depression and examined the specific autonomic nervous system mechanisms underlying the responses. Sprague-Dawley rats exposed to a series of mild, unpredictable stressors over 4 wk displayed anhedonia (an essential feature of human depression), along with elevated resting heart rate, decreased heart rate variability, and exaggerated pressor and heart rate responses to air jet stress. Results obtained from experiments studying autonomic blockade suggest that cardiovascular alterations in the chronic mild stress model are mediated by elevated sympathetic tone to the heart. The present findings have implications for the study of pathophysiological links between affective disorders and cardiovascular disease.     

Production and purification of urokinase: a comprehensive review

An increased emphasis on prevention of fatalities due to thrombovascular disorders is broadening opportunities for several cardiovascular agents, especially plasminogen activators, for preventing strokes and heart attacks. Hence, urokinase, as one of the most potent plasminogen activators is attracting a great deal of attention. Developments in cell lines and bioprocess technology have made it possible to produce urokinase from in vitro cell culture. Attempts are now underway to enhance urokinase production from cell culture through media manipulation, bioreactor cultivation, and innovative purification techniques. Downstream processing also poses an intricate problem due to the complexity of cell culture extracts, susceptibility of urokinase to autocatalytic and proteolytic degradation and due to the presence of plasminogen activator inhibitors in the culture media. Hence, enhancing cellular productivity and downstream product recovery continue to be major challenges as discussed in this review. Furthermore, an approach for integrated upstream and downstream processing is needed to develop an economically viable technology. In the present review the emerging trends in urokinase production and purification have been discussed in detail.     

Fabry disease

Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, whereas dialysis or renal transplantation are available for patients experiencing end-stage renal failure. With age, progressive damage to vital organ systems develops and at some point, organs may start to fail in functioning. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated males and females with reductions of 20 and 10 years, respectively, as compared to the general population. While there is increasing evidence that long-term enzyme therapy can halt disease progression, the importance of adjunctive therapies should be emphasized and the possibility of developing an oral therapy drives research forward into active site specific chaperones.     

Asymmetric dimethylarginine in children with homocystinuria or phenylketonuria

Plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis from l-arginine and a cardiovascular risk factor, was found to be elevated in plasma of homocysteinemic adults. Enhanced cardiovascular risk due to homocystinuria and impaired renal function has been found in patients with phenylketonuria (PKU) on protein-restricted diet. However, it is still unknown whether ADMA synthesis is also elevated in children with homocystinuria due to cystathionine beta-synthase deficiency (classical homocystinuria), and whether ADMA may play a role in phenylketonuria in childhood. In the present study, we investigated the status of the l-arginine/NO pathway in six young patients with homocystinuria, in 52 young phenylketonuria patients on natural protein-restricted diet, and in age- and gender-matched healthy children serving as controls. ADMA in plasma and urine was determined by GC–MS/MS. The NO metabolites nitrate and nitrite in plasma and urine, and urinary dimethylamine (DMA), the dimethylarginine dimethylaminohydrolase (DDAH) metabolite of ADMA, were measured by GC–MS. Unlike urine ADMA excretion, plasma ADMA concentration in patients with homocystinuria was significantly higher than in controls (660 ± 158 vs. 475 ± 77 nM, P = 0.035). DMA excretion rate was considerably higher in children with homocystinuria as compared to controls (62.2 ± 24.5 vs. 6.5 ± 2.9 μmol/mmol creatinine, P = 0.068), indicating enhanced DDAH activity in this disease. In contrast and unexpectedly, phenylketonuria patients had significantly lower ADMA plasma concentrations compared to controls (512 ± 136 vs. 585 ± 125 nM, P = 0.009). Phenylketonuria patients and controls had similar l-arginine/ADMA molar ratios in plasma. Urinary nitrite excretion was significantly higher in phenylketonuria as compared to healthy controls (1.7 ± 1.7 vs. 0.7 ± 1.2 μmol/mmol creatinine, P = 0.003). Our study shows that the l-arginine/NO pathway is differently altered in children with phenylketonuria and homocystinuria. Analogous to hyperhomocysteinemic adults, elevated ADMA plasma concentrations could be a cardiovascular risk factor in children with homocystinuria. In phenylketonuria, the l-arginine/NO pathway seems not be altered. Delineation of the role of ADMA in childhood phenylketonuria and homocystinuria demands further investigation.     

Protective effect of oestradiol on the heart of rats exposed to acute ischaemia

Sex-related differences in mortality from ischaemic heart disease are attributed chiefly to difference in the incidence of atherosclerosis. Little attention has been paid to the influence of sex hormones on resistance of the myocardium itself to acute ischaemia. Experiments on rats showed that isolated female hearts were more resistant than male hearts. A period of eight weeks spent at an altitude of 1,350 m raised heart resistance only in males. Conversely, gonadectomy abruptly reduced the resistance of the male heart to ischaemia, especially under conditions of mild altitude hypoxia. The administration of oestradiol to gonadectomized male rats largely abolished the disturbance caused by isolated gonadectomy. Since coronary vasoconstriction and vasospasm lead to temporary ischaemia and even to infarction, the above effect of the sex hormones may play a role in the increased incidence of heart attacks after the gonads have ceased to function.     

Diabetes and hypertension

Diabetes mellitus and hypertension constitute two powerful independent risk factors for cardiovascular, renal and atherosclerotic disease. The frequent occurrence of the two diseases in the same individual doubles the risk of cardiovascular death, as well as substantially increasing the frequency of transient ischemic attacks, strokes, peripheral vascular disease with lower extremity amputations, as well as end-stage renal disease and blindness. Although hypertension usually occurs in IDDM in association with renal disease, in NIDDM the evolution of hypertension appears to be multifactorial and independent of renal disease. Obesity appears to be dissociable from hypertension and NIDDM with a common link between obesity, hypertension and NIDDM appearing to be hyperinsulinism and insulin resistance. It has been suggested that hyperinsulinism and insulin resistance may lead to hypertension through altered intracellular calcium metabolism, enhanced renal sodium reabsorption, or through an effect of insulin upon lipid and/or catecholamine metabolism. Further, insulin itself may have a direct effect upon the atherosclerotic process in the hypertensive diabetic patient. These considerations have been taken into account in the structuring of antihypertensive therapy in Type I and Type II Diabetes Mellitus.     

Role of dietary magnesium in cardiovascular disease prevention, insulin sensitivity and diabetes

PURPOSE OF REVIEW: This review summarizes the evidence for benefits of magnesium on metabolic abnormalities, inflammatory parameters, and cardiovascular risk factors and related-potential mechanisms. Controversy due to contrasting results in the literature is also discussed. RECENT FINDINGS: Increased dietary magnesium intake confers protection against the incidence of diabetes, metabolic syndrome, hypertension, and cardiovascular disease. It ameliorates insulin resistance, serum lipid profiles, and lowers inflammation, endothelial dysfunction, oxidative stress, and platelet aggregability. Magnesium acts as a mild calcium antagonist on vascular smooth muscle tone, and on postreceptor insulin signaling; it is critically involved in energy metabolism, fatty acid synthesis, glucose utilization, ATPase functions, release of neurotransmitters, and endothelial cell function and secretion. Prospective studies, however, have found only a modest effect for dietary magnesium on incident pathologies. Furthermore, magnesium supplementation on glucose metabolism, blood lipid levels, and ischemic heart disease has given inconsistent results. SUMMARY: There is strong biological plausibility for the direct impact of magnesium intake on metabolic and cardiovascular risk factors, but in-vivo magnesium deficiency might play only a modest role. Reverse causality, the strong association between magnesium and other beneficial nutrients, or the possibility that people who choose magnesium-rich foods are more health-conscious may be confounding factors.     

Coronary and cardiovascular risk estimation for primary prevention: validation of a new Sheffield table in the 1995 Scottish health survey population

ObjectiveTo examine the accuracy of a new version of the Sheffield table designed to aid decisions on lipids screening and detect thresholds for risk of coronary heart disease needed to implement current guidelines for primary prevention of cardiovascular disease.DesignComparison of decisions made on the basis of the table with absolute risk of coronary heart disease or cardiovascular disease calculated by the Framingham risk function. The decisions related to statin treatment when coronary risk is ⩾30% over 10 years; aspirin treatment when the risk is ⩾15% over 10 years; and the treatment of mild hypertension when the cardiovascular risk is ⩾20% over 10 years.SettingThe table is designed for use in general practice.SubjectsRandom sample of 1000 people aged 35-64 years from the 1995 Scottish health survey.Results13% of people had a coronary risk of ⩾15%, and 2.2% a risk of ⩾30%, over 10 years. 22% had mild hypertension (systolic blood pressure 140-159 mm Hg). The table indicated lipids screening for everyone with a coronary risk of ⩾15% over 10 years, for 95% of people with a ratio of total cholesterol to high density lipoprotein cholesterol of ⩾8.0, but for <50% with a coronary risk of <5% over 10 years. Sensitivity and specificity were 97% and 95% respectively for a coronary risk of ⩾15% over 10 years; 82% and 99% for a coronary risk of ⩾30% over 10 years; and 88% and 90% for a cardiovascular risk of ⩾20% over 10 years in mild hypertension.ConclusionThe table identifies all high risk people for lipids screening, reduces screening of low risk people by more than half, and ensures that treatments are prescribed appropriately to those at high risk, while avoiding inappropriate treatment of people at low risk.     

Body weight: implications for the prevention of coronary heart disease,stroke, and diabetes mellitus in a cohort study of middle aged men.

OBJECTIVE: To determine the body mass index associated with the lowest morbidity and mortality. DESIGN: Prospective study of a male cohort. SETTING: One general practice in each of 24 British towns. SUBJECTS: 7735 men aged 40-59 years at screening. MAIN OUTCOME MEASURES: All cause death rate, heart attacks, and stroke (fatal and non-fatal) and development of diabetes, or any of these outcomes (combined end point) over an average follow up of 14.8 years. RESULTS: There were 1271 deaths from all causes, 974 heart attacks, 290 strokes, and 245 new cases of diabetes mellitus. All cause mortality was increased only in men with a body mass index (kg/m2) < 20 and in men with an index > or = 30. However, risk of cardiovascular death, heart attack, and diabetes increased progressively from an index of < 20 even after age, smoking, social class, alcohol consumption, and physical activity were adjusted for. For the combined end point the lowest risks were seen for an index of 20.0-23.9. In never smokers and former smokers, deaths from any cause rose progressively from an index of 20.0-21.9 and for the combined end point, from 20.0-23.9. Age adjusted levels of a wide range of cardiovascular risk factors rose or fell progressively from an index < 20. CONCLUSION: A healthy body mass index in these middle aged British men seems to be about 22.     

Molecular genetics of MTHFR: polymorphisms are not all benign

Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate and homocysteine metabolism. Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia. Shortly thereafter, we identified the 677C-->T variant and showed that it encoded a thermolabile enzyme with reduced activity. Currently, a total of 41 rare but deleterious mutations in MTHFR, as well as about 60 polymorphisms have been reported. The 677C-->T (Ala222Val) variant has been particularly noteworthy since it has become recognized as the most common genetic cause of hyperhomocysteinemia. The disruption of homocysteine metabolism by this polymorphism influences risk for several complex disorders, including cardiovascular disease, neural tube defects and some cancers. We describe here the complex structure of the MTHFR gene, summarize the current state of knowledge on rare and common mutations in MTHFR and discuss some relevant findings in a mouse model for MTHFR deficiency.     

Cardiovascular disease prevention and treatment

The incidence of fatal and non-fatal cardiovascular disease (sudden cardiac death (SCD), myocardial infarction, others) varies, depending on conventional risk factors. However, in Western countries, like the US or Germany, incidences of fatal and non-fatal cardiovascular disease are far higher than in countries like Japan. In the present article, these differences are discussed and related to eicosapentaenoic acid (C20:5omega-3 or C20:5n-3; EPA) and docosahexaenoic acid (C22:6omega-3; DHA). Dietary intake of EPA and DHA and a number of other factors determine levels of EPA and DHA in an individual—best assessed as the omega-3 index, defined as the percentage of EPA and DHA in red cells, and analyzed in a standardized fashion. A review of the literature, expanded by measurements of the omega-3 index, indicates that the risk of sudden cardiac death correlates inversely with the omega-3 index. For persons with an omega-3 index <4%, risk is tenfold, as compared to persons with an omega-3 index >8%. A similar, less-pronounced, correlation exists for non-fatal cardiovascular disease. EPA and DHA have anti-arrhythmic and anti-atherosclerotic mechanisms of action. In large-scale intervention studies, intake of EPA and DHA has been demonstrated to reduce SCD and non-fatal cardiovascular events. Assessing or recommending dietary intake of EPA and DHA does not predict the resulting omega-3 index. Taken together, the omega-3 index is a biomarker to assess a person's content of omega-3 fatty acids, and thus the risk for sudden cardiac death, as well as non-fatal cardiovascular events. EPA and DHA prevent fatal and non-fatal cardiovascular disease and complications of congestive heart failure.     

Gender differences in coronary heart disease

Cardiovascular disease develops 7 to 10 years later in women than in men and is still the major cause of death in women. The risk of heart disease in women is often underestimated due to the misperception that females are ‘protected’ against cardiovascular disease. The under-recognition of heart disease and differences in clinical presentation in women lead to less aggressive treatment strategies and a lower representation of women in clinical trials. Furthermore, self-awareness in women and identification of their cardiovascular risk factors needs more attention, which should result in a better prevention of cardiovascular events. In this review we summarise the major issues that are important in the diagnosis and treatment of coronary heart disease in women. (Neth Heart J 2010;18:598–603.)     

A review on coronary artery disease,its risk factors,and therapeutics

Coronary artery disease (CAD) is one of the major cardiovascular diseases affecting the global human population. This disease has been proved to be the major cause of death in both the developed and developing countries. Lifestyle, environmental factors, and genetic factors pose as risk factors for the development of cardiovascular disease. The prevalence of risk factors among healthy individuals elucidates the probable occurrence of CAD in near future. Genome-wide association studies have suggested the association of chromosome 9p21.3 in the premature onset of CAD. The risk factors of CAD include diabetes mellitus, hypertension, smoking, hyperlipidemia, obesity, homocystinuria, and psychosocial stress. The eradication and management of CAD has been established through extensive studies and trials. Antiplatelet agents, nitrates, β-blockers, calcium antagonists, and ranolazine are some of the few therapeutic agents used for the relief of symptomatic angina associated with CAD.     

Inflammation and atherosclerosis in rheumatoid arthritis

Rheumatoid arthritis (RA) associates with increased cardiovascular mortality. This appears to be predominantly due to ischaemic causes, such as myocardial infarction and congestive heart failure. The higher prevalence of cardiac ischaemia in RA is thought to be due to the accelerated development of atherosclerosis. There are two main reasons for this, which might be inter-related: the systemic inflammatory load, characteristic of RA; and the accumulation in RA of classical risk factors for coronary heart disease, which is reminiscent of the metabolic syndrome. We describe and discuss in the context of RA the involvement of local and systemic inflammatory processes in the development and rupture of atherosclerotic plaques, as well as the role of individual risk factors for coronary heart disease. We also present the challenges facing the clinical and scientific communities addressing this problem, which is receiving increasing attention.