Vascular Disease Morbidity Research Articles

Health Promotion in Older Chinese

Aging, in conjunction with decreasing physical activity, is associated with a range of health problems. Simple, low-maintenance, population-based means of promoting activity to counteract the age-associated decline are required. We therefore assessed the effect of pedometry and buddy support to increase physical activity. We undertook a clustered randomized trial (HKCTR-346) of 24 community centers involving 399 older Chinese participants (≥ 60 yr). Centers were randomly allocated to 1) pedometry and buddy, 2) pedometry and no buddy, 3) no pedometry and buddy, and 4) no pedometry and no buddy with a 2 × 2 factorial design. The trial simultaneously tested the individual and combined effects of the interventions. The intervention groups also received monthly organized group activities to provide encouragement and support. Outcome measures were assessed at 6 and 12 months, including physical fitness and activity and cardiovascular disease risk factors (anthropometry and blood pressure). From the 24 centers, 356 volunteers (89.2%) completed the study. Those receiving the interventions had higher mean physical activity levels at 12 months of 1820 (95% confidence interval (CI) = 1360-2290) and 1260 (95% CI = 780-1740) MET·min·wk(-1), respectively relative to the decrease in the control groups. The buddy peer support intervention significantly improved mean aerobic fitness (12% [95% CI = 4%-21%]) and reduced both body fat (-0.6% [95% CI = -1.1% to 0.0%]) and time to complete the 2.5-m get-up-and-go test (-0.27 [95% CI = -0.53 to -0.01] s). No other improvements in the cardiovascular disease risk factors were observed. The combination of motivational tools was no better than the individual interventions. Both motivational interventions increased physical activity levels, and the buddy style improved fitness. These tools could be useful adjuncts in the prevention of obesity and age-related complications.

Higher incidence of C677T polymorphism of the MTHFR gene in North Indian patients with vascular disease

Homocysteine is a sulfur-containing amino acid, which is derived from dietary methionine. Hyperhomocysteinemia has been implicated in vascular disease for over a decade now, and can be treated with B vitamins. Among its causes is polymorphism of the MTHFR gene, the most common being the cytidine to thymidine at position 677 (MTHFR C677T), which gives rise to three genotypes - normal homozygous CC, heterozygous CT and homozygous variant TT. An attempt was made to ascertain the prevalence of this MTHFR C677T in our population so that preventive measures may accordingly be instituted. Blood samples from 70 patients with vascular disease and 70 healthy controls were analyzed for plasma homocysteine levels (chemiluminescent immunoassay) and for the presence of MTHFR C677T (polymerase chain reaction analysis). Homocysteine was higher in the homozygous subjects (TT genotype) than in the heterozygous (CT genotype). In patients, the frequency of the C allele was significantly lower, and that of the T allele was significantly higher than the corresponding frequencies in controls. In conclusion, the North Indian urban population has higher homocysteine levels associated with the TT genotype. Hence, instituting measures towards reduction of homocysteine levels in the population would probably reduce the incidence and morbidity of vascular disease in our population.

Lowering homocysteine and modifying nutritional status with folic acid and vitamin B12 in Indian patients of vascular disease

Hyperhomocysteinemia is more commonly associated with vascular disease in Indians than in the western populations. It is caused by genetic polymorphisms or dietary deficiencies of the B vitamins. We attempted to identify the association of hyperhomocysteinemia with vitamin B12 and folate in Indian patients of vascular disease. Homocysteine, vitamin B12 and folate levels were estimated in 100 controls and 100 patients of vascular disease. Homocysteine estimation was repeated in 73 patients on different vitamin supplements for 6 months. Homocysteine exhibited a significant negative correlation with B12 only in cerebrovascular disease and peripheral vascular diseasepatients, and with folate in coronary artery disease and cerebrovascular disease patients as well as controls. Single daily dose of folate was as effective as a combination of folate and cobalamin in reducing plasma homocysteine concentrations. Low levels of B12 contribute to the higher incidence of cerebrovascular disease and peripheral vascular disease, and low folate levels account for higher prevalence of hyperhomocysteinemia in coronary artery disease and cerebrovascular disease. Moreover, irrespective of the cause of hyperhomocysteinemia, folate is known to ameliorate it. Hence, large-scale corrective measures like food fortification or dietary supplementation with folate might benefit the Indian population and reduce the incidence and morbidity of vascular disease.

Clinical factors in patients with ischemic versus hemorrhagic stroke in East China.

Stroke is one of the leading causes of mortality and morbidity of vascular diseases, and its incidence maintains at a high level around the world. In China, stroke has been a major public health problem. Because the pathogenesis of ischemic stroke is different from that of hemorrhagic stroke, their clinical factors would not be the same. Therefore to investigate the different effects of various effect factors on ischemic versus hemorrhagic stroke and then to enhance the prevention are crucial to decrease the incidence. A total of 692 patients, consisting of 540 ischemic stroke patients and 152 hemorrhagic stroke patients from East China, were included in this study. The related factors of stroke subtypes were collected and analyzed. The factors significantly associated with ischemic stroke as opposed to hemorrhagic stroke were family history of stroke, obesity, atherosclerotic plaque of the common carotid artery, atrial fibrillation, hyperfibrinogenemia, transient ischemic attack (TIA), atherosclerotic plaque of the internal carotid artery, coronary heart, lower high-density lipoproteins (lower HDL), increasing age, diabetes mellitus, and gender (male) (P<0.05). Leukocytosis, hypertension and family history of hypertension were the significant factors associated with hemorrhagic stroke versus ischemic stroke. Smoking, drinking, kidney diseases and lower HDL-C were the significant factors contributing to ischemic stroke in man. Obesity, family history of hypertension, family history of stroke, hypercholesteremia and myocardial ischemia were the significant factors for females with ischemic stroke. The most prominent factors for overall stroke in East China were hypertension, followed by higher pulse pressure and hypercholesteremia. The factors for ischemic and hemorrhagic stroke are not the same. Different effects of risk factors on stroke are found in male and female patients.

Thrombus resolution and vein wall injury: dependence on chemokines and leukocytes

Chronic venous insufficiency resulting in post-thrombotic syndrome occurs commonly after acute deep vein thrombosis, and is a prevalent cause of vascular disease morbidity in the community. Therefore, a better understanding of the pathophysiologic mechanisms that promote the development of chronic venous insufficiency could lead to novel approaches to interrupt the natural history and prevent post-thrombotic syndrome. In this paper, we will review the evidence that venous thrombus resolution is an inflammatory process that is dependent on chemokines and leukocytes.

Primary Intracerebral Hemorrhage Mortality Reduction After Installation of a Tap-Water Supply System in an Arseniasis-Endemic Area in Southwestern Taiwan

Mortality and morbidity of vascular diseases, including stroke, are known to be associated with chronic exposure to inorganic arsenic through drinking water. A tap-water supply system was implemented in the early 1960s in the blackfoot disease (BFD) endemic areas of Taiwan. The objective of this study was to examine whether mortality attributed to stroke decreased among residents living in the BFD-endemic areas after the curtailment of arsenic exposure. Further it was of interest to determine whether arsenic exposure was related to a specific type of stroke. Standardized mortality ratios (SMRs) for stroke were calculated for the BFD endemic area for the years 1971–2000. The study results show that mortality due to primary intracerebral hemorrhage (PIH) declined gradually after the improvement of drinking-water supply system by elimination of arsenic exposure through removal of artesian well water. Based on the reversibility and specificity criteria, the association between arsenic exposure and mortality due to PIH is likely to be causal.

Differential association of C-reactive protein with adiposity in men and women in an Aboriginal community in northeast Arnhem Land of Australia

To examine the relationship between C-reactive protein (CRP), adiposity and other metabolic abnormalities in an Aboriginal community in Northern Australia. Cross-sectional analysis of data obtained between 2001 and 2003 from 379 Aboriginal people residing in a geographically isolated community. Mean (95% CI) CRP in women and men was 4.06 cholesterol (3.53, 4.66) mg/l and 3.42 (2.94, 3.97) mg/l, respectively (P=NS). The prevalence of the metabolic syndrome (US National Cholesterol Education [corrected] Program (NCEP) definition) was significantly higher for women than men (41 vs 18%, chi (2)=20.94, P<0.001). C-reactive protein correlated strongly with adiposity in women (waist circumference, waist to hip ratio and body mass index; r>/=0.514, P<0.01) but much less strongly in men (r</=0.221, P<0.05). In a multivariate stepwise linear regression model, waist circumference was the strongest independent predictor explaining 35% of CRP concentration variance in women, but only 5.4% in men (WHR). Incremental increases in CRP concentration across four BMI categories were significant in women (P (linear trend)<0.001) but not in men. High CRP levels in the surveyed population are consistent with the high prevalence of vascular disease morbidity and mortality in Aboriginal Australians. The relationship of CRP with increasing body fat was strong and consistent in women but not in men. Prospective studies are needed to elucidate the role of CRP (if any) as a predictive marker for cardiovascular events in this high-risk population.

Leukocytosis, Vascular Disease, and Adenine Nucleotide Metabolism

To the Editor: We read with interest the paper by Barry S. Coller on leukocytosis and its relationship with vascular disease morbidity and mortality1 and the subsequent correspondence.2,3 We are intrigued to learn that relative leukocytopenia may be associated with increased morbidity and mortality in patients with acute myocardial infarction1,4 and in those undergoing percutaneous coronary intervention.5 We note the discussion on whether leukocyte count is merely a marker of general disturbances in inflammation and general poor health, or whether leukocytes might contribute directly to thrombosis and atherosclerosis. Although several mechanisms through which leukocytes may contribute to thrombosis and atherosclerosis were discussed,1–3 nothing has been said about the role of leukocytes in adenine nucleotide metabolism. Adenosine diphosphate (ADP) is, of course, a major contributor to the thrombotic mechanism as evidenced by the successful use of ADP antagonists which reduce ADP-induced platelet activation and aggregation and thereby act as anti-thrombotic agents.6 It was recognized that leukocytes are active in the metabolism of adenine nucleotides many years …

Neutrophil Count and Complex Lesions in Patients With Coronary Artery Disease

To the Editor: In a recent article, Coller1 reviews the role of leukocytosis in vascular disease morbidity and mortality. Despite the exhaustive nature of the review, we were concerned that the author failed to address an issue of major importance, namely the relationship between neutrophil count and the presence of vulnerable atheromatous plaques in patients with coronary artery disease. Acute coronary syndromes result mainly from occlusive coronary artery thrombosis at sites of plaque fissure, rupture, or superficial erosion. At angiography, disrupted or ulcerated plaques often appear as “complex” stenoses with rough …

Leukocytosis and Ischemic Vascular Disease Morbidity and Mortality

The association between leukocytosis and increased morbidity and mortality of ischemic vascular disease has been observed for more than half a century, and recent studies in >350,000 patients confirm the robustness of the association and the dramatically higher relative and absolute acute and chronic mortality rates in patients with high versus low leukocyte counts. Although there is reason to believe that the association is not causal (that is, that leukocytosis is simply a marker of inflammation), there is also reason to believe that the leukocytosis directly enhances acute thrombosis and chronic atherosclerosis. Leukocytosis also is associated with poor prognosis and vaso-occlusive events in patients with sickle cell disease, and experimental data suggest a direct role for leukocytes in microvascular obstruction. The only way to test whether leukocytes contribute directly to poor outcome in ischemic cardiovascular disease is to assess the effect of modifying leukocyte function or number. Because selective blockade of leukocyte integrin alphaMbeta2 and P-selectin have thus far been disappointing as therapeutic strategies in human cardiovascular and cerebrovascular disease, I discuss the potential risks and benefits of short-term treatment with hydroxyurea to decrease the leukocyte count in select populations of patients at the highest risk of short-term death.

Protein S declines during winter respiratory infections

There is an increase in cardiovascular and cerebrovascular morbidity and mortality in the older adult population during the winter that could be related to prothrombotic changes caused by seasonal effects or acute respiratory tract infections. Therefore, a prospective cohort study was conducted to assess the effect of acute winter respiratory infection on hemostatic parameters including complement 4b-binding protein (C4-BP), functional protein S, total protein S, free protein S, and the inflammatory marker, interleukin-6 (IL-6), in younger and older adults. The changes in the levels of hemostatic and inflammatory markers during winter respiratory infections in the younger and older adults were compared with matched, non-infected controls. In younger and older adults (combined), total protein S increased from 83% [95% confidence interval (CI); 77-88] to 98% (95% CI; 91-106, P < 0.001) while free protein S decreased from 100% (95% CI; 95-105) to 70% (95% CI; 66-75, P < 0.001). There were no significant changes in C4-BP (P = 0.622), functional protein S (P = 0.061) or IL-6 (P = 0.651) from baseline. In a multivariate analysis, only total protein S and free protein S showed significant association with seasonal change after adjusting for the effect of infection. The estimated effect of season on total protein S was 15 +/- 4%, P < 0.001 and on free protein S was -27 +/- 3%, P < 0.001. After adjusting for seasonal effect, only functional protein S showed a significant association with infection, with the estimated effect of -17 +/- 5%, P < 0.001. The results in the younger and older adults were similar to those in the combined groups. Seasonal and infection-related changes in hemostatic parameters including an increase in fibrinogen and a decrease in free protein S, observed in this study, may contribute to thrombotic risk and excess vascular disease morbidity and mortality in older populations in the winter season.

Effect of MTHFR 677C>T on plasma total homocysteine levels in renal graft recipients

Hyperhomocysteinemia is an established, independent risk factor for vascular disease morbidity and mortality. The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T has been shown to result in increased total homocysteine concentrations on the basis of low folate levels caused by a decreased enzyme activity. The effect of this polymorphism on total homocysteine and folate plasma levels in renal transplant patients is unknown. We screened 636 kidney graft recipients for the presence of the MTHFR C677T gene polymorphism. The major determinants of total homocysteine and folate plasma concentrations of 63 patients, who were identified to be homozygous for this gene polymorphism compared with heterozygotes (N = 63), and patients with wild-type alleles (N = 63), who were matched for sex, age, glomerular filtration rate (GFR), and body mass index, were identified by analysis of covariance. The variables included sex, age, GFR, body mass index, time since transplantation, folate and vitamin B12 levels, the use of azathioprine, and the MTHFR genotype. To investigate the impact of the kidney donor MTHFR genotype on total homocysteine and folate plasma concentrations, a similar model was applied in 111 kidney graft recipients with stable graft function, in whom the kidney donor C677T MTHFR gene polymorphism was determined. The allele frequency of the C677T polymorphism in the MTHFR gene was 0.313 in the whole study population [wild-type (CC), 301; heterozygous (CT), 272; and homozygous mutant (TT), 63 patients, respectively] and showed no difference in the patient subgroups with various renal diseases. The MTHFR C677T gene polymorphism significantly influenced total homocysteine and folate plasma concentrations in renal transplant recipients (P = 0.0009 and P = 0.0002, respectively). Furthermore, a significant influence of the GFR (P = 0.0001), folate levels (P = 0.0001), age (P = 0.0001), body mass index (P = 0.0001), gender (P = 0.0005), and vitamin B12 levels (P = 0.004) on total homocysteine concentrations was observed. The donor MTHFR gene polymorphism had no influence on total homocysteine and folate levels. Geometric mean total homocysteine levels in patients homozygous for the mutant MTHFR allele were 18.6 micromol/liter compared with 14.6 micromol/liter and 14.9 micromol/liter in patients heterozygous for the MTHFR gene polymorphism and those with wild-type alleles (P < 0.05 for TT vs. CT and CC). Geometric mean folate levels were lower in CT and TT patients (11.2 and 10.2 nmol/liter) compared with CC patients (13.6 nmol/liter, P < 0.05 vs. CT and TT). This study demonstrates that homozygosity for the C677T polymorphism in the MTHFR gene significantly increases total homocysteine concentrations and lowers folate levels in kidney graft recipients, even in patients with excellent renal function (GFR more than median). These findings have important implications for risk evaluation and vitamin intervention therapy in these patients who carry an increased risk for the development of cardiovascular disease.