Major Cardiovascular Disease Risk Research Articles

Association Between Length of Residence and Cardiovascular Disease Risk Factors Among an Ethnically Diverse Group of United States Immigrants

Although differences in cardiovascular disease (CVD) risk factors between immigrants and nonimmigrants have been examined previously, the effect of acculturation on CVD risk factors in immigrants has been less well studied. To determine the association between length of U.S. residence (proxy for acculturation) and major CVD risk factors. Data on 5,230 immigrant adults from the 2002 National Health Interview Survey (NHIS) was analyzed. Primary independent variable was length of U.S. residence < 10, 10 to < 15, and > or = 15 years. Main outcome measures included obesity, hypertension, diabetes, hyperlipidemia, smoking, and physical inactivity. Multiple logistic regression was used to assess the association between length of residence and odds of multiple CVD risk factors adjusting for confounders. SAS-callable SUDAAN was used for statistical analysis. Among the patients, 55.4% were obese, 17.3% had hypertension, 15.9% had hyperlipidemia, 6.6% had diabetes, 79.3% were physically inactive, and 14.3% were smokers. Using < 10 years as reference, those with length of residence > or = 15 years were more likely to be obese (OR 1.31, 95% CI 1.03-1.65), have hyperlipidemia (OR 1.59, 95% CI 1.14-2.22), and be smokers (OR 1.39, 95% CI 1.04-1.85). Length of residence > or = 15 years was associated with decreased odds of sedentary lifestyle (OR 0.63, 95% CI 0.47-0.84). Length of residence > or = 15 years was not associated with odds of having diabetes (OR 1.40, 95% CI 0.78-2.51) or hypertension (OR 1.21, 95% CI 0.86-1.71). Among immigrants from diverse ethnic backgrounds, longer length of residence in the United States is associated with increased odds of obesity, hyperlipidemia, and cigarette smoking even after adjusting for relevant confounding factors.

The Relationship Between Total Cholesterol and the Risk of Major Cardiovascular Diseases is Similar Amongst Individuals With and Without Diabetes Across Populations in the Asia Pacific Region

The Relationship Between Total Cholesterol and the Risk of Major Cardiovascular Diseases is Similar Amongst Individuals With and Without Diabetes Across Populations in the Asia Pacific Region

Diabetes is Associated with Alterations in the Dystrophin Glycoprotein Complex Composition in the Heart Muscle

BACKGROUND: Obesity and diabetes pose a major risk for cardiovascular disease and are associated with an increased incidence of heart failure. Myocardial dystrophin disruption has been shown to be a major cause of advanced heart failure. Whether diabetes is associated with the dystrophin glycoprotein complex (DGC) composition in the myocardium is not known. PURPOSE: We compared the expression of various components of the DGC in hearts of normal lean and obese Zucker rats, an established model of syndrome-X, exhibiting type II diabetes. METHODS: Immunoblotting and immunohistochemical analyses were performed on cell membrane and cytosolic fractions of hearts obtained from normal lean Zucker (LNZ) rats and diabetic obese Zucker (OSXZ) rats to examine the expression and localization of components of the DGC. RESULTS: Immunoblot analysis revealed markedly higher cytoplasmic dystrophin content (39.95 ± 3.7% over control) as compared to control lean hearts, with no significant difference in the membrane dystrophin content. The content of á-dystroglycan was 35.99 ± 2.9% and 34.74 ± 2.5% higher in the membrane and cytosolic fractions of the OSXZ hearts as compared to the LNZ hearts. The cytosolic content of ß-dystroglycan was 49.84 ± 6.4% higher in the OSXZ hearts as compared to LNZ hearts, while the membrane content was 24.82% higher. CONCLUSION: These preliminary data suggest a difference in composition of the DGC between the normal and syndrome-X Zucker rat hearts. (Supported by funds from NSF Grant 0314742).

Letter by Kurth Regarding Article, “Nonsteroidal Antiinflammatory Drugs, Acetaminophen, and the Risk of Cardiovascular Events”

To the Editor: The study by Chan and colleagues1 evaluated the association between use of nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen and the risk of major cardiovascular disease in apparently healthy women. Their study showed a statistically significant increased risk among women who used NSAIDs or acetaminophen ≥22 days per month. In their discussion, the authors cited a secondary analysis from the Physicians’ Health Study that regular NSAID use (use of NSAIDS ≥60 days per year) was associated with a nearly 3-fold higher risk of …

Perinatal and childhood origins of cardiovascular disease

Features of the metabolic syndrome comprise a major risk for cardiovascular disease and will increase in prevalence with rising childhood obesity. We sought to identify early life influences on development of obesity, hypertension and dyslipidemia in children. Cluster analysis was used on a subset of a longitudinal Australian birth cohort who had blood samples at age 8 (n=406). A quarter of these 8-year-olds fell into a cluster with higher body mass index, blood pressure (BP), more adverse lipid profile and a trend to higher serum glucose resembling adult metabolic syndrome. There was a U-shaped relationship between percentage of expected birth weight (PEBW) and likelihood of being in the high-risk cluster. The high-risk cluster had elevated BP and weight as early as 1 and 3 years old. Increased likelihood of the high-risk cluster group occurred with greatest weight gain from 1 to 8 years old (odds ratio (OR)=1.4, 95% confidence interval (CI)=1.3-1.5/kg) and if mothers smoked during pregnancy (OR=1.82, CI=1.05-3.2). Risk was lower if children were breast fed for >/=4 months (OR=0.6, 95% CI=0.37-0.97). Newborns in the upper two quintiles for PEBW born to mothers who smoked throughout pregnancy were at greatest risk (OR=14.0, 95% CI=3.8-51.1) compared to the nadir PEBW quintile of non-smokers. A U-shaped relationship between birth weight and several components of the metabolic syndrome was confirmed in a contemporary, well-nourished Western population of full-term newborns, but post-natal weight gain was the dominant factor associated with the high-risk cluster. There was a prominence of higher as well as lowest birth weights in those at risk. Future health programs should focus on both pre- and post-natal factors (reducing excess childhood weight gain and smoking during pregnancy), and possibly the greatest benefits may arise from targeting the heaviest, as well as lightest newborns, especially with a history of maternal smoking during pregnancy.

Plasma Fibrinogen Level and the Risk of Major Cardiovascular Diseases and Nonvascular Mortality: An Individual Participant Meta-analysis—Correction

Plasma Fibrinogen Level and the Risk of Major Cardiovascular Diseases and Nonvascular Mortality: An Individual Participant Meta-analysis—Correction

Plasma Fibrinogen Level and the Risk of Major Cardiovascular Diseases and Nonvascular Mortality

Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Increased Prevalence of Third-Degree Atrioventricular Block in Patients With Type II Diabetes Mellitus

Diabetes mellitus (DM) is a major risk for cardiovascular disease and mortality. There is some evidence that third-degree atrioventricular (AV) block occurs more commonly in patients with DM. In this study, we evaluated any possible association between DM and third-degree AV block using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in a very large inpatient database. We used patient treatment files containing discharge diagnoses using ICD-9 codes of inpatient treatment from all Veterans Health Administration hospitals. The cohort was stratified using the ICD-9-CM code for DM (n = 293,124), a control group with hypertension but no DM (n = 552,623), and the ICD-9 code for third-degree AV block (426.0) and smoking (305.1, V15.82). We performed multivariate analysis adjusting for coronary artery disease, congestive heart failure, smoking, and hyperlipidemia. Continuous and binary variables were analyzed using chi2 and Fisher exact tests. Third-degree AV block diagnosis was present in 3,240 of DM patients (1.1%) vs 3,367 patients (0.6%) in the control group. Using multivariate analysis, DM remained strongly associated with third-degree AV block (odds ratio, 3.1; 95% confidential interval, 3.0 to 3.3; p < 0.0001). Third-degree AV block occurs significantly more in patients with DM. This finding may, in part, explain the high cardiovascular mortality in DM patients.

Dysmetabolic syndrome in childhood and adolescence

The dysmetabolic syndrome, consisting of dyslipidaemia, hypertension, hyperinsulinaemia and central obesity, has been well recognized as a major risk for cardiovascular disease in adults. Although the clustering of cardiovascular risk factors has also been identified in childhood, the occurrence of full-blown dysmetabolic syndrome at younger ages has only recently been investigated. In this article we attempted an overview of the data for children and adolescents, focused on the mechanisms and natural history of the disease, the prevalence among paediatric populations, the assessment and the treatment approaches. There is substantial evidence that the dysmetabolic syndrome has its origins in childhood. In the face of the epidemic increase of obesity in children and adolescents, the development of effective screening and preventive strategies would be a major challenge for paediatricians.

Dysmetabolic syndrome in childhood and adolescence

The dysmetabolic syndrome, consisting of dyslipidaemia, hypertension, hyperinsulinaemia and central obesity, has been well recognized as a major risk for cardiovascular disease in adults. Although the clustering of cardiovascular risk factors has also been identified in childhood, the occurrence of full-blown dysmetabolic syndrome at younger ages has only recently been investigated. In this article we attempted an overview of the data for children and adolescents, focused on the mechanisms and natural history of the disease, the prevalence among paediatric populations, the assessment and the treatment approaches. Conclusion: There is substantial evidence that the dysmetabolic syndrome has its origins in childhood. In the face of the epidemic increase of obesity in children and adolescents, the development of effective screening and preventive strategies would be a major challenge for paediatricians.

Aging hearts and vessels: Masters of adaptation and survival

Aging has become one of the most critical issues for industrialised nations, because population average age, and thus the incidence of age-associated disease, has markedly risen to create a major burden as patients draw heavily on the need for continuing medical treatment and hospital and other community services. Despite major advances in medicine in recent years, cardiovascular disease remains the greatest cause of morbidity and mortality. Age, per se, confers the major risk for cardiovascular disease because specific pathophysiological mechanisms that underlie these diseases become superimposed on cardiac and vascular substrates that have been modified by the “aging process” [1–3]. In healthy humans rigorously screened to exclude cardiovascular disease, non-human primates, and rodents, the large elastic arteries become dilated and stiffen and the intima thickens and exhibits cellular and sub-cellular features that resemble those that occur during vascular inflammation and injury [1]. Age-associated changes in cardiac structure (increased left ventricular myocyte size, reduced myocyte number, increased extracellular matrix remodelling, fibrosis) and resting function (reduced early diastolic filling) occur, in part, in response to aging of the arterial system [2]. Cardiovascular reserve function in advanced aged without cardiovascular disease is limited by suboptimal ventricular–vascular coupling due to an age-associated augmentation of vascular afterload and reduced myocardial contractility due, in part, to a diminished effectiveness of β-adrenergic modulation [3,4]. Senescent cardiac myocytes are characterized by altered metabolic, ionic, and electrical properties due partly to increased myocyte size, altered membrane composition, reduced capacity to maintain ion homeostasis, reduced Ca2+ tolerance, increased reactive O2 species levels in response to a variety of stressors, and reduced adaptive capacity to invoke “ischemic preconditioning-like” intracellular signal transduction for post-stress survival [5–9]. Age-targeted therapies such as those involving diet, exercise habits, gene therapy, or pharmacological agents that interfere with or beneficially … *Corresponding author. Laboratory of Cardiac Surgical Research, Alfred Hospital and Baker Heart Research Institute, POB 6492 St. Kilda Rd. Central, Melbourne, VIC 8008, Australia. Tel.: +61 3 85321310; fax: +61 3 85321314. Email address: spepe{at}baker.edu.au

Direct effects of sex steroid hormones on adipose tissues and obesity.

Sex steroid hormones are involved in the metabolism, accumulation and distribution of adipose tissues. It is now known that oestrogen receptor, progesterone receptor and androgen receptor exist in adipose tissues, so their actions could be direct. Sex steroid hormones carry out their function in adipose tissues by both genomic and nongenomic mechanisms. In the genomic mechanism, the sex steroid hormone binds to its receptor and the steroid-receptor complex regulates the transcription of given genes. Leptin and lipoprotein lipase are two key proteins in adipose tissues that are regulated by transcriptional control with sex steroid hormones. In the nongenomic mechanism, the sex steroid hormone binds to its receptor in the plasma membrane, and second messengers are formed. This involves both the cAMP cascade and the phosphoinositide cascade. Activation of the cAMP cascade by sex steroid hormones would activate hormone-sensitive lipase leading to lipolysis in adipose tissues. In the phosphoinositide cascade, diacylglycerol and inositol 1,4,5-trisphosphate are formed as second messengers ultimately causing the activation of protein kinase C. Their activation appears to be involved in the control of preadipocyte proliferation and differentiation. In the presence of sex steroid hormones, a normal distribution of body fat exists, but with a decrease in sex steroid hormones, as occurs with ageing or gonadectomy, there is a tendency to increase central obesity, a major risk for cardiovascular disease, type 2 diabetes and certain cancers. Because sex steroid hormones regulate the amount and distribution of adipose tissues, they or adipose tissue-specific selective receptor modulators might be used to ameliorate obesity. In fact, hormone replacement therapy in postmenopausal women and testosterone replacement therapy in older men appear to reduce the degree of central obesity. However, these therapies have numerous side effects limiting their use, and selective receptor modulators of sex steroid hormones are needed that are more specific for adipose tissues with fewer side effects.

5,10-Methylenetetrahydrofolate reductase 677C-->T and 1298A-->C mutations are genetic determinants of elevated homocysteine.

Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of homocysteine metabolism. Elevated plasma total homocysteine (tHcy) is a major risk for cardiovascular disease. A common 677C-->T mutation in the MTHFR gene results in decreased enzymic activity, and contributes to increased plasma tHcy, in association with low plasma folate. A recently described 1298A-->C mutation in the MTHFR gene clearly reduces MTHFR activity (although to a lesser extent than the 677C-->T) but its effect on plasma tHcy levels is not yet clear. To investigate the frequency of these two MTHFR polymorphisms in a Portuguese population, and to correlate the MTHFR genotype with the biochemical phenotype at the level of homocysteine and folate concentrations. Prospective population survey. We studied 117 healthy volunteers (71 females, 46 males). The 677C-->T and 1298A-->C mutations were screened by PCR-RFLP. Levels of plasma tHcy and folate, and red blood cell folate, were determined. The allele frequencies of the 677C-->T and 1298A-->C mutations were 0.33 and 0.28, respectively. Homozygotes for the 677C-->T mutation had significantly elevated plasma tHcy and RBC folate levels and significantly lowered plasma folate concentrations than subjects without the mutation. The 1298A-->C mutation showed a significant effect on plasma tHcy, but not on plasma folate or RBC folate levels. The observed 677T allele frequency is not consistent with the idea of a north-south gradient as previously suggested. The 1298A-->C mutation is common in Portugal. Both MTHFR mutations showed effects on plasma tHcy levels.

Assessment of in vivo oxidative stress in hypertensive rats and hypertensive subjects in Tanzania, Africa.

Oxidative stress has been reported to be involved in not only cardiovascular diseases but in hypertension, which is a major risk for cardiovascular diseases. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been recognized as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. In the present study, we assessed the oxidative stress in human subjects with hypertension and in hypertensive rats. In stroke-prone spontaneously hypertensive rats at the age of 14 weeks, the excretion of urinary 8-OHdG was significantly (p < 0.05) increased compared with that in age-matched normotensive Wistar-Kyoto rats. Next, we investigated the relationship between oxidative DNA damage and cardiovascular risk factors among Tanzanians aged 46-58 years in a population study carried out in 1998 in at Dar es Salaam, Tanzania, according to the WHO-CARDIAC Study Protocol. Sixty subjects (male/female, 28/32) were selected by SPSS Base 8.0 from those who completed a 24-h urine collection. The 24-h urinary 8-OHdG of the hypertensive subjects (SBP > or =140 mmHg and/or DBP > or =90 mmHg) was significantly (p < 0.05) higher than that of the normotensive subjects (SBP <140 mmHg and DBP <90 mmHg) after adjusting for age and gender (Hypertensives: 17.31 +/- 2.0 ng/mg creatinine, n=38; Normotensives: 10.10 +/- 2.64 ng/mg creatinine, n=22). Oxidative stress was thought to be involved in hypertensive subjects and in hypertensive rats.

Impact of body weight and weight loss on cardiovascular risk factors

Overwieght and obesity are classified as a major risk for cardiovascular disease (CVD). An increase in the body mass index is associated with adverse changes in the plasma lipid and lipoprotein profile resulting in elevated total cholesterol, low-density lipoprotein-cholesterol, and triglyceride levels and a decrease in high-density lipoprotein levels. An android pattern of obesity is associated with a more deleterious plasma lipoprotein profile as well as hypertension and insulin resistance, resulting in an even greater increase in CVD risk. Weight loss through caloric restriction improves the plasma lipoprotein profile. A Step-1 diet plus exercise confer even greater benefits.