History Of Clinical Cardiovascular Disease Research Articles

Hearing Sensitivity in Older Adults: Associations with Cardiovascular Risk Factors in the Health, Aging and Body Composition Study

To examine the association between cardiovascular disease (CVD) and its risk factors and age-associated hearing loss in a cohort of older black and white adults. Cross-sectional cohort study. The Health, Aging, and Body Composition (Health ABC) Study, a community-based cohort study of older adults from Pittsburgh, Pennsylvania, and Memphis, Tennessee. Two thousand forty-nine well-functioning adults (mean age 77.5; 37% black). Pure-tone audiometry measurement and history of clinical CVD were obtained at the fourth annual follow-up visit. Pure-tone averages in decibels reflecting low (250, 500, and 1,000 Hz), middle (500, 1,000, and 2,000 Hz), and high (2,000, 4,000, and 8,000 Hz) frequencies were calculated for each ear. CVD risk factors, aortic pulse-wave velocity (PWV), and ankle-arm index (AAI) were obtained at study baseline. In sex-stratified models, after adjustment for age, race, study site, and occupational noise exposure, risk factors associated with poorer hearing sensitivity in men included high triglyceride levels, high resting heart rate, and history of smoking. In women, poor hearing sensitivity was associated with high body mass index, high resting heart rate, fast PWV, and low AAI. Modifiable risk factors for CVD may play a role in the development of age-related hearing loss.

Antihypertensive Treatment and Secondary Prevention of Cardiovascular Disease Events Among Persons Without Hypertension

Cardiovascular disease (CVD) risk increases beginning at systolic blood pressure levels of 115 mm Hg. Use of antihypertensive medications among patients with a history of CVD or diabetes and without hypertension has been debated. To evaluate the effect of antihypertensive treatment on secondary prevention of CVD events and all-cause mortality among persons without clinically defined hypertension. Meta-analysis with systematic search of MEDLINE (1950 to week 3 of January 2011), EMBASE, and the Cochrane Collaboration Central Register of Controlled Clinical Trials and manual examination of references in selected articles and studies. From 874 potentially relevant publications, 25 trials that fulfilled the predetermined inclusion and exclusion criteria were included in the meta-analysis. Information on participant characteristics, trial design and duration, treatment drug, dose, control, and clinical events were extracted using a standardized protocol. Outcomes included stroke, myocardial infarction (MI), congestive heart failure (CHF), composite CVD outcomes, CVD mortality, and all-cause mortality. Compared with controls, participants receiving antihypertensive medications had a pooled relative risk of 0.77 (95% confidence interval [CI], 0.61 to 0.98) for stroke, 0.80 (95% CI, 0.69 to 0.93) for MI, 0.71 (95% CI, 0.65 to 0.77) for CHF, 0.85 (95% CI, 0.80 to 0.90) for composite CVD events, 0.83 (95% CI, 0.69 to 0.99) for CVD mortality, and 0.87 (95% CI, 0.80 to 0.95) for all-cause mortality from random-effects models. The corresponding absolute risk reductions per 1000 persons were -7.7 (95% CI, -15.2 to -0.3) for stroke, -13.3 (95% CI, -28.4 to 1.7) for MI, -43.6 (95% CI, -65.2 to -22.0) for CHF events, -27.1 (95% CI, -40.3 to -13.9) for composite CVD events, -15.4 (95% CI, -32.5 to 1.7) for CVD mortality, and -13.7 (95% CI, -24.6 to -2.8) for all-cause mortality. Results did not differ according to trial characteristics or subgroups defined by clinical history. Among patients with clinical history of CVD but without hypertension, antihypertensive treatment was associated with decreased risk of stroke, CHF, composite CVD events, and all-cause mortality. Additional randomized trial data are necessary to assess these outcomes in patients without CVD clinical recommendations.

Letter: Diabetic Polyneuropathy and Cardiovascular Complications in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:390-6)

Letter: Diabetic Polyneuropathy and Cardiovascular Complications in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:390-6)

Is Diabetic Retinopathy Related to Subclinical Cardiovascular Disease?

Persons with diabetic retinopathy (DR) have an increased risk of clinical cardiovascular events. This study aimed to determine whether DR is associated with a range of measures of subclinical cardiovascular disease (CVD) in persons without clinical CVD. Population-based, cross-sectional epidemiologic study. Nine hundred twenty-seven persons with diabetes without clinical CVD in the Multi-Ethnic Study of Atherosclerosis. Diabetic retinopathy was ascertained from retinal photographs according to modification of the Airlie House Classification system. Vision-threatening DR (VTDR) was defined as severe nonproliferative DR, proliferative DR, or clinically significant macular edema. Subclinical CVD measures were assessed and defined as follows: high coronary artery calcium (CAC) score, defined as CAC score of 400 or more; low ankle-brachial index (ABI), defined as ABI of less than 0.9; high ABI, defined as ABI of 1.4 or more; high carotid intima-media thickness (IMT), defined as highest 25% of IMT; and carotid stenosis, defined as more than 25% stenosis or presence of carotid plaque. Associations between DR and subclinical CVD measures. The prevalence of DR and VTDR in this sample was 30.0% and 7.2%, respectively, and VTDR was associated with a high CAC score (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.15-4.73), low ABI (OR, 2.54; 95% CI, 1.08-5.99), and high ABI (OR, 12.6; 95% CI, 1.14-140.6) after adjusting for risk factors including hemoglobin A1c level and duration of diabetes. The association between VTDR and high CAC score remained significant after further adjustment for hypoglycemic, antihypertensive, and cholesterol-lowering medications. Diabetic retinopathy was not significantly associated with measures of carotid artery disease. In persons with diabetes without a history of clinical CVD, the presence of advanced-stage DR is associated with subclinical coronary artery disease. These findings emphasize the need to be careful about the use of anti-vascular endothelial growth factor for the treatment of DR.

Plasma osteoprotegerin, arterial stiffness, and mortality in normoalbuminemic Japanese hemodialysis patients

A high circulating osteoprotegerin (OPG) level may be a risk factor for vascular calcification and mortality in hemodialysis patients. OPG and pulse wave velocity (PWV) were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients who were prospectively followed for 6 years. In long-term normoalbuminemic Japanese hemodialysis patients, OPG levels were strongly linked with both arterial stiffness and worse outcome. A high circulating OPG level is reported to be a risk factor for vascular calcification and mortality in Western chronic kidney disease (CKD) patients but it is not known if this is true for Japanese CKD patients, where a different risk profile may operate. OPG and PWV were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients (median age 62 years) who were prospectively followed for 6 years. OPG levels were associated in multivariate analysis with age, dialysis vintage, history of cardiovascular disease (CVD) and parathyroid hormone levels. C-reactive protein levels did not correlate with OPG. Patients with clinical history of CVD had significantly higher OPG levels and OPG levels were positively correlated to PWV, an index of arterial stiffness. These associations were independent of age, sex, dialysis vintage, and diabetes. During the follow-up period, 40 deaths, including 25 cardiovascular deaths, were recorded. In crude analysis, each unit of increase in OPG was associated with increased all-cause (hazard ratios 1.14, 95% confidence interval 1.08-1.20) and CVD mortality (1.14 [1.07-1.21]), which persisted after adjustment for age, sex, dialysis vintage, diabetes, and baseline CVD (1.12 [1.05-1.19] and 1.11 [1.02-1.19], all-cause and CVD mortality, respectively). In long-term normoalbuminemic Japanese hemodialysis patients, with low prevalence of inflammation, OPG levels were strongly linked with both arterial stiffness and worse outcome.

Association of Optimism and Pessimism With Inflammation and Hemostasis in the Multi-Ethnic Study of Atherosclerosis (MESA)

To investigate the association between optimism/pessimism and concentrations of seven inflammation and hemostasis markers. Optimism and pessimism are associated with cardiovascular disease mortality and progression; however, the biological mechanism remains unclear. This cross-sectional study used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a study of 6814 persons aged 45 to 84 years with no history of clinical cardiovascular disease. The Life-Orientation Test-Revised (LOT-R) was used to measure dispositional optimism and pessimism. Regression analyses were used to estimate associations of optimism and pessimism with interleukin (IL)-6, C-reactive protein (CRP), fibrinogen, homocysteine, Factor VIII, D-dimer, and plasmin-antiplasmin, before and after adjustment for sociodemographics, depression, cynicism, health behaviors, body mass index (BMI), hypertension, and diabetes. Higher scores on the LOT-R (positive disposition) were related to lower concentrations of IL-6 (p = .001), fibrinogen (p < .001), and homocysteine (p = .031). Associations were stronger for the pessimism subscale. After adjustment for demographics, the percentage differences in inflammatory markers corresponding to a 2-standard deviation increase in pessimism were 6.01% (p = .001) for IL-6, 10.31% (p = .001) for CRP, 2.47% (p < .0001) for fibrinogen, and 1.36% (p = .07) for homocysteine. Associations were attenuated but significant after adjustment for sociodemographics, depression, cynical distrust, and behaviors. Further adjustment for hypertension, BMI, and diabetes reduced associations for CRP and IL-6. Pessimism remained associated with a 1.36% (p = .02) increase in fibrinogen in the fully adjusted model. Factor VIII, D-dimer, and plasmin-antiplasmin were not associated with the LOT-R or subscales. Pessimism is related to higher levels of inflammation. Health behaviors, BMI, hypertension, and diabetes seem to play a mediating role.

The High Prevalence of Subclinical Atherosclerosis in Patients With Ankylosing Spondylitis Without Clinically Evident Cardiovascular Disease

We conducted the present study to determine whether subclinical macrovascular atherosclerotic disease was present in patients with ankylosing spondylitis (AS) without clinical history of cardiovascular disease. We also sought to establish whether demographic or clinical features of the disease may influence the development of subclinical atherosclerotic disease in a series of patients with AS seen at a community hospital. We recruited 64 patients who fulfilled the modified New York diagnostic criteria for AS from Hospital Xeral-Calde, Lugo, Spain. We excluded patients seen during the recruitment period who had cardiovascular disease or renal insufficiency. We also studied 64 matched controls. Carotid artery intima-media thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high-resolution B-mode ultrasound.Patients with AS exhibited greater carotid IMT than did matched controls (mean +/- SD, 0.74 +/- 0.21 mm vs. 0.67 +/- 0.14 mm; p = 0.01; differences of means, 0.077; 95% confidence interval, 0.016-0.139). Carotid plaques were more commonly observed in patients with AS than in controls (19 [29.7%] vs. 6 [9.4%], respectively; p = 0.03). The best predictors for carotid plaques in patients with AS were erythrocyte sedimentation rate (ESR) at time of disease diagnosis (odds ratio [OR], 1.18; 95% confidence intervals [CI], 1.04-1.33; p = 0.01) and duration of disease (OR, 1.39; 95% CI, 1.01-1.92; p = 0.05). In contrast, there was no significant correlation between carotid IMT and either ESR or C-reactive protein in this study. Results of the present study show that patients with AS without clinically evident cardiovascular disease have a high prevalence of subclinical macrovascular disease in the form of increased carotid IMT and carotid plaques compared to matched controls.

Grosor de la íntima-media carotídea en la hipercolesterolemia familiar heterocigótica: factores asociados y variación al año de tratamiento

Background and objective To evaluate the factors associated with intima-media thickness (IMT) and carotid plaques in patients with familial hypercholesterolemia (FH) and to assess the evolution following 1 year of treatment. Patients and method Subjects (n=201) diagnosed as having probable or definite FH according to the MED-PED criteria had a clinical history, physical examination, blood chemistry and lipid profile determined. Ultrasound was used to measure the IMT in both common carotid arteries and to assess the presence of plaques. The measurements were repeated in 123 of the patients after 1 year of treatment. Results Mean age (standard deviation) was 47.8 (13.2) years; 46.3% were males; 11.4% had a clinical history of cardiovascular disease (CVD); 15.9% were hypertensive; 26.4% were smokers; mean plasma total cholesterol concentration was 362 (49) mg/dL; 66.2% had received previous treatment with statins. In the multivariate analysis, baseline IMT was directly associated with age and history of CVD and inversely related to the years of treatment with statins. The presence of carotid plaques was associated directly with the cholesterol-years index and inversely with years of treatment with statins. The mean LDL-cholesterol reduction at 1 year of treatment was 50%. Neither the IMT nor the percentage of patients with plaques changed significantly following 1 year of treatment. Conclusions Intensive hypocholesterolemic treatment in our patients with probable or definite FH did not increase significantly either the carotid IMT or the prevalence of plaques.

Low serum testosterone increases mortality risk among male dialysis patients.

Men treated with hemodialysis (HD) have a very poor prognosis and an elevated risk of premature cardiovascular disease (CVD). In the general population, associations between low testosterone concentrations and cardiovascular risk have been suggested. We performed a prospective observational study involving a well characterized cohort of 126 men treated with HD to examine the relationship between testosterone concentration and subsequent mortality during a mean follow-up period of 41 mo. Independent of age, serum creatinine, and sexual hormone binding globulin (SHBG), testosterone levels inversely and strongly associated with the inflammatory markers IL-6 and CRP. Patients with a clinical history of CVD had significantly lower testosterone levels. During follow up, 65 deaths occurred, 58% of which were a result of CVD. Men with testosterone values in the lowest tertile had increased all-cause and CVD mortality (crude hazard ratios [HRs] 2.03 [95% CI 1.24 to 3.31] and 3.19 [1.49 to 6.83], respectively), which persisted after adjustment for age, SHBG, previous CVD, diabetes, ACEi/ARB treatment, albumin, and inflammatory markers, but was lost after adjustment for creatinine. In summary, among men treated with HD, testosterone concentrations inversely correlate with all-cause and CVD-related mortality, as well as with markers of inflammation. Hypogonadism may be an additional treatable risk factor for patients with chronic kidney disease.

Life at the Extreme Limit: Phenotypic Characteristics of Supercentenarians in Okinawa

As elite representatives of the rapidly increasing "oldest-old" population, centenarians have become an important model population for understanding human aging. However, as we are beginning to understand more about this important phenotype, another demographic group of even more elite survivors is emerging-so-called "supercentenarians" or those who survive 110-plus years. Little is known about these exceptional survivors. We assessed the Okinawa Centenarian Study (OCS) database for all information on supercentenarians. The database includes dates of birth and year of death for all residents of Okinawa 99 years old or older and a yearly geriatric assessment of all centenarians who consented, enabling prospective study of age-related traits. Of 20 potential supercentenarians identified, 15 had agreed to participate in the OCS interview, physical examination, and blood draw. Of these 15, 12 (3 men and 9 women) met our age validation criteria and were accepted as supercentenarians. Phenotypic variables studied include medical and social history, activities of daily living (ADLs), and clinical phenotypes (physiology, hematology, biochemistry, and immunology). Age at death ranged from 110 to 112 years. The majority of supercentenarians had minimal clinically apparent disease until late in life, with cataracts (42%) and fractures (33%) being common and coronary heart disease (8%), stroke (8%), cancer (0%), and diabetes (0%) rare or not evident on clinical examination. Functionally, most supercentenarians were independent in ADLs at age 100 years, and few were institutionalized before the age of 105 years. Most had normal clinical parameters at age 100 years, but by age 105 exhibited multiple clinical markers of frailty coincident with a rapid ADL decline. Supercentenarians displayed an exceptionally healthy aging phenotype where clinically apparent major chronic diseases and disabilities were markedly delayed, often beyond age 100. They had little clinical history of cardiovascular disease and reported no history of cancer or diabetes. This phenotype is consistent with a more elite phenotype than has been observed in prior studies of centenarians. The genetic and environmental antecedents of this exceptionally healthy aging phenotype deserve further study.

Abstract 3648: Clinical Cardiovascular Disease in Women is Associated With Increased Epicardial, but Not Subcutaneous Fat Thickness

INTRODUCTION: Visceral adipose tissue, such as epicardial fat, is metabolically active, and may portend increased risk for cardiovascular disease (CVD) compared to subcutaneous fat. Cardiovascular magnetic resonance (CMR) can accurately delineate fat, but data are sparse regarding the relationship of epicardial and subcutaneous fat burden to CVD in community-living adult women. METHODS: 957 women (aged 64± 8 years) in the Framingham Heart Study Offspring cohort, followed by serial examinations since 1974, underwent CMR on a 1.5-T Philips system using an ECG-gated cine SSFP sequence. Epicardial fat thickness (EFT) over the midlevel right ventricle was measured from a 4-chamber view. Suprasternal subcutaneous fat thickness (SFT) was measured at the main pulmonary artery level. We compared EFT and SFT between women with clinical CVD, documented by a physician endpoint committee (+CVD), vs. those without (noCVD) based on Cycle 7 (1998 –2002) clinical data. Differences were assessed by two-sample T-test; ANOVA was used to adjust for age, diabetes, hypertension and menopausal status. RESULTS: The +CVD group comprised 74 (8%) women who were older and more likely to be postmenopausal, diabetic and hypertensive than noCVD women (Table ). EFT was greater in +CVD (10.5 ± 5.1mm) vs. noCVD (8.6 ± 5.2mm) groups, p&lt;0.003. This difference remained significant after adjusting for age, diabetes, hypertension and menopausal status (Table ). No difference in SFT or body mass index was observed between groups (p=NS). CONCLUSIONS: Women with history of clinical CVD have greater EFT than women without CVD, and this difference persists after adjustment for common cardiovascular risk factors. However, subcutaneous fat, as assessed by chest wall adiposity, did not differ between groups. EFT may be a useful marker for cardiovascular risk, and prospective investigation of the relationship between EFT and future risk for CVD is warranted.

Association between serum uric acid level and peripheral arterial disease

Background Higher serum uric acid levels have been implicated in the development and progression of atherosclerotic cardiovascular disease. However, it is not clear whether serum uric acid levels are related to subclinical measures of cardiovascular disease, including peripheral arterial disease (PAD). We examined the association between increasing serum uric acid levels and PAD in the US general population. Methods A cross-sectional study was conducted among 3987 National Health and Nutrition Examination Survey 1999–2002 participants aged ≥40 years, without clinical history of cardiovascular disease. Main outcome-of-interest was PAD defined as ankle-brachial index <0.9 ( n = 229). Results Higher serum uric acid levels were positively associated with PAD, independent of smoking, body mass index (BMI), hypertension, diabetes, serum total cholesterol, serum creatinine, and other confounders. Multivariable odds ratio (OR) [95 percent confidence intervals (CI)] comparing serum uric acid levels ≥75th percentile (≥380.8 μmol/L) to uric acid levels <50th percentile (<315.6 μmol/L) was 1.62 (1.08–2.44), p-trend = 0.015. This association persisted in separate analysis among men and women. Further, the results were consistent in subgroup analyses by categories of age, current smoking, BMI, and diabetes mellitus. Conclusions Higher serum uric acid levels are associated with PAD in the US general population. These results suggest that PAD may be an important indicator of the reported association between higher serum uric acid levels and clinical cardiovascular disease. Future prospective studies are required to clarify the temporal nature of this relationship.

Coronary Artery Atherosclerosis Is Related to Reduced Regional Left Ventricular Function in Individuals Without History of Clinical Cardiovascular Disease

We investigated whether regional coronary calcium score by computed tomography is related to regional left ventricular systolic function measured by MRI tagging in participants of the Multiethnic Study of Atherosclerosis. The Multiethnic Study of Atherosclerosis is a prospective observational study of men and women without a history of previous heart disease from 4 ethnic groups. Calcium scores were measured separately for the left anterior descendent (LAD), left circumflex (LCX), and right (RCA) coronary arteries. Left ventricular strain and strain rate were determined by tagged MRI in the corresponding vascular territories of the coronary vessels in 509 participants. Greater coronary calcification in the LAD, LCX, and right RCA coronary arteries were related to worse function in their respective perfusion. Anterior wall strain rate was -1.37+/-0.41 when LAD calcium was zero versus -1.17+/-0.24 1/s in the highest quartile of calcium score (P<0.001). Similar relationships were evident in the LCX and RCA regions. Participants with 1- and 2-vessel coronary artery calcium had better myocardial function in the remote area compared with the territory supplied by the diseased artery. High-local calcium score is related to regional dysfunction in the corresponding coronary territory among individuals without a history of previous heart disease. These results indicate a link between atherosclerosis and subclinical regional left ventricular dysfunction.

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 and -2 in type 2 diabetes: effect of 1 year's cardiovascular risk reduction therapy.

Cardiovascular risk reduction therapy in diabetic patients reduces vascular events (1) by retarding atherosclerosis and improving vascular reactivity. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are integral to the vascular changes of atheroma, and MMP-9 and TIMP-1 are raised in diabetes (2). We hypothesized that global risk reduction of intensified diabetes and cardiovascular risk management in type 2 diabetes would be associated with reductions in circulating markers of extracellular matrix turnover, namely MMP-9, TIMP-1, and TIMP-2. ### Cross-sectional study Eighty-six patients with type 2 diabetes (3) and treated hypertension with serum creatinine <120 mmol/l were recruited from local clinics (Table 1). Of these, 46% ( n = 36) had a clinical history of cardiovascular disease. Data from these patients were compared with 49 healthy control subjects. Ethical approval and informed consent were obtained. ### Interventional study Sixty-five of the recruited diabetic patients (of whom 36 had cardiovascular disease) consented to intensified diabetes and cardiovascular risk management therapy. This consisted of 3 monthly consultations, lifestyle advice, and adjusting oral hypoglycemia therapy to achieve HbA 1c 25 kg/m 2 or added second-line in lean patients, who received initial treatment with gliclazide MR (30 mg o.d.) and vice versa. Insulin could be started if HbA 1c remained >7.0% despite …

Lipid profile, BMI, body fat distribution, and aerobic fitness in men with metabolic syndrome.

Obesity, impaired glucose tolerance, type 2 diabetes, hyperlipidemia, hypertension, and insulin resistance are wellknown components of metabolic syndrome and are associated to increased cardiovascular morbidity. The present study aimed to evaluate the relationships between cardiorespiratory fitness, body fat distribution, and selected coronary heart disease risk factors. A total of 22 untrained subjects affected by one or more features of metabolic syndrome and without clinical history of cardiovascular disease were studied. Nondiabetic subjects underwent an oral glucose tolerance test for glucose and insulin measurement; fasting glucose and insulin were measured in diabetic patients. Complete lipid profile, thyroid hormones, and thyroid-stimulating hormone were measured in all subjects. Basal energy expenditure and cardiorespiratory fitness were measured using a K4 analyzer. Cardiorespiratory fitness ( VO(2max)/kg) was assessed using a treadmill graded exercise test. Peak aerobic capacity ( VO(2max)/kg) was predicted by body fat distribution, insulin sensitivity index, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol ( p<0.001). A significant relationship was found between cardiorespiratory fitness ( VO(2max)/kg) and body mass index (BMI), insulin sensitivity index, and LDL cholesterol ( r=0.60, p<0.05; r=0.66, p<0.01 and r=0.54, p<0.05, respectively). Data demonstrated that aerobic fitness is related to metabolic parameters and to body fat distribution, and suggest that its modification may improve well-known predictors of coronary artery disease.

Single pill could reduce risk of cardiovascular disease by over 80%

A combination pill containing six different drugs could reduce mortality from strokes and myocardial infarctions by 88%, according to a recent study in the BMJ (2003;326:1419-22). Dubbed the “polypill,” it would be intended as a preventive measure and be taken once daily by everyone over 55 years of age and younger people with a clinical history of cardiovascular disease. The researchers, Nicholas Wald and Malcolm Law, from Queen Mary's School of Medicine and Dentistry, London, performed a series of meta-analyses of existing data on the …

Determinants of fasting plasma total homocysteine levels among chronic stable renal transplant recipients.

Although several studies have demonstrated an unadjusted association between folate status and fasting plasma total homocysteine (tHcy) levels among renal transplant recipients, no data confirming the strength or independence of this association have been reported. We determined fasting plasma folate, B12, and pyridoxal 5'-phosphate (active vitamin B6) levels, along with other potential determinants of plasma tHcy levels (i.e., age, sex, creatinine levels, and Cockcroft-Gault estimated creatinine clearance, current immunosuppressive regimen, and history of clinical cardiovascular disease), among 86 renal transplant recipients. The recipients were > or =6 months after transplantation, lived in the Providence, Rhode Island metropolitan area, and were examined between February and June 1998. Stepwise general linear modeling with analysis of covariance revealed that only creatinine level, age, and vitamin status were independent regressors (i.e., P<0.100) of tHcy levels. Moreover, creatinine level alone determined most of the variability in tHcy levels (i.e., R2) accounted for by these independent variables (R2=0.416 for creatinine level alone; total R2=0.575). In contrast, the R2 for folate alone was only 0.046, and even for all three B vitamins combined, the R2 was just 0.088. We conclude that renal function is the overriding independent determinant of fasting tHcy levels among stable renal transplant recipients. In comparison to renal function, vitamin status has a relatively marginal influence on tHcy levels and cyclosporine use has essentially none at all.

Stressful events as a trigger of sudden death: a study of 43 medico-legal autopsy cases

The reports relating emotional stress to sudden death are largely anecdotal. In addition to experimental and electrophysiological studies, an opportunity for a better understanding of possible stress-related sudden death (SSD) may be provided by medico-legal autopsies. The goal of our autopsy study was to analyze cardiovascular pathologic findings in cases of SSD and if possible identify mechanisms by which the stressful event (SE) could be the cause. Forty three cases were studied (29 males and 14 females). In all cases, the SE and the death were witnessed. The age range was 22 to 90 years in males (mean, 52) and 30 to 92 years in females (mean, 64). Death occurred in all cases without premonitory symptoms. In 20 cases, death occurred during the SE and in the other 23 cases occurred within 2 h of the event. SE included fear, 15 cases; altercation, 21 cases; sexual activity, 3 cases; police questioning or arrest, 4 cases. According to police reports, in 40 cases (90%), the victims had no previous clinical history of cardiovascular disease. At autopsy, the heart weight in males ranged from 255 to 1000 g with a mean of 517 g and in females the range was 250–700 g with a mean of 417 g. In only 3 cases, gross and microscopic examination of the heart was normal. In 2 of the remaining 40 cases the subjects died of subarachnoid hemorrhage. In 38 cases, a cardiac cause of death was found as follows: coronary heart disease, 27 cases; cardiomyopathy, 6 cases; aortic valvular stenosis, 2 cases and right ventricular dysplasia, 3 cases. A coronary artery thrombosis was found in 8 cases of sudden coronary death. Post myocardial infarction fibrosis was present in 25 cases (92%) of sudden coronary death. In conclusion, it appears from our autopsy study that SSD occurs primarily in those individuals with severe heart disease, especially coronary heart disease.

Fibrinogen and Factor VIII, but Not Factor VII, Are Associated With Measures of Subclinical Cardiovascular Disease in the Elderly

No studies have examined the associations of coagulation factor levels with measures of subclinical cardiovascular disease (CVD) in the elderly. The Cardiovascular Health Study (CHS) is a prospective, population-based cohort study of CVD in persons older than 65 years. At the baseline examination, we measured fibrinogen, factor VII, and factor VIII levels in 5024 of the 5201 participants of the CHS and examined the associations of these coagulation factors with measures of subclinical CVD in a cross-sectional analysis. Subclinical CVD measures were based on electrocardiography, carotid ultrasonography, echocardiography, and ankle-arm blood pressure measurements (AAI). For analyses, we used the full cohort as well as two mutually exclusive subgroups: those with prevalent clinical CVD at baseline and those without. Fibrinogen and to a lesser extent factor VIII showed positive associations with a variety of subclinical CVD measures. In age-adjusted analyses, fibrinogen and factor VIII were significantly associated with 8 of 10 measures. In multivariate analyses, fibrinogen was significantly associated with carotid artery stenosis, internal (but not common) carotid artery wall thickness, and AAI. Factor VIII was associated with abnormal wall motion and AAI in the full cohort only. Factor VII was not consistently associated with subclinical disease measures. In bivariate analyses that included data from all three groups, there were 5 positive subclinical disease associations and 5 negative associations for factor VII. In multivariate analyses, there were no significant associations between factor VII and subclinical CVD in the full cohort or in either subgroup. We conclude that in these cross-sectional analyses, fibrinogen and to a lesser extent factor VIII are associated with subclinical CVD in the elderly, even in those without symptoms or a history of clinical CVD. Factor VII, however, was not associated with subclinical CVD in the elderly.

The relationship between ankle brachial index, other atherosclerotic disease, diabetes, smoking and mortality in older men and women

The goal of this study is to investigate the relationship between peripheral arterial disease and mortality in a large patient population and assess the effects of other atherosclerotic diseases, diabetes and smoking on this relationship. All patients, 50 years or older and with no history of lower extremity surgery, evaluated for lower extremity arterial disease in a university hospital peripheral vascular laboratory over a 13-year period (1977–1989) were included in the study ( n = 1930). Arterial disease was assessed by measurement of the resting ankle brachial index (ABI) in these patients. The ABI was calculated by dividing the systolic pressure in the tibial arteries by the pressure in the brachial artery. Analyses of the data by use of multivariate statistical techniques and by stratification of the patient population by co-morbid condition indicate that ABI is a robust and independent predictor of all-cause mortality in both men (relative risk (RR) = 1.6,95% confidence interval (CI)1.3, 2.0) and women (RR = 1.9,95% CI 1.4, 2.4). The relative risks are essentially unchanged after exclusion of all patients with clinical history of cardiovascular disease or diabetes. Similarly, a low ABI is an important risk factor for mortality among patients with a history of stroke, angina or diabetes; men and women with a history of smoking and women who are non-smokers. Therefore, the measurement of ABI, a simple, objective, non-invasive technique which can be used in the physician's office, may be useful for early identification of patients at high risk for morbidity and mortality.