Are predictors of coronary heart disease and lower-extremity arterial disease in type 1 diabetes the same? A prospective study.

In the Type 1 diabetes population, coronary heart disease (CHD) and lower-extremity arterial disease (LEAD) are the two common macrovascular complications leading to early mortality and morbidity. However, it is not clear if these two complications share the same risk factors. The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study prospectively examined and compared the risk factors for LEAD and CHD (including CHD morbidity and mortality). EDC subjects (332 men and 325 women), all diagnosed at Children's Hospital of Pittsburgh between 1950 and 1980, were first examined at baseline (1986-1988), and then biennially, for diabetes complications and their risk factors. Data used in the current analysis were from the first 6 years of follow-up, 98% provided at least some follow-up data for these analyses. CHD was defined as the presence of angina (diagnosed by the EDC examining physician) or a history of confirmed myocardial infarction or CHD death. An ankle-to-arm ratio of less than 0.9 at rest was considered to be evidence of LEAD. Among 635 subjects without CHD at baseline, 57 developed CHD (1.69/100 person-years), and among 579 without LEAD at baseline, 70 developed LEAD (2.31/100 person-years). CHD incidence rate was slightly higher in males, while LEAD incidence rate was slightly higher in females. Compared to non-incident cases, subjects who developed either complication were older, had a longer diabetes duration, higher LDL and total cholesterol, and were more likely to be hypertensive. In multivariate analyses, hypertension, low HDL cholesterol level, high white cell count, depression, and nephropathy were the independent risk factors for CHD (including morbidity and mortality). For LEAD, higher HbA1 level, higher LDL cholesterol level and smoking were the important contributing factors. In conclusion, the risk factor patterns differ between the two vascular complications. Glycemic control does not predict CHD overall but does predict LEAD, while hypertension and inflammatory markers are more closely related to CHD than to LEAD.

Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group.

BACKGROUND: The combined thickness of the intima and media of the carotid artery is associated with the prevalence of cardiovascular disease. We studied the associations between the thickness of the carotid-artery intima and media and the incidence of new myocardial infarction or stroke in persons without clinical cardiovascular disease. METHODS: Noninvasive measurements of the intima and media of the common and internal carotid artery were made with high-resolution ultrasonography in 5858 subjects 65 years of age or older. Cardiovascular events (new myocardial infarction or stroke) served as outcome variables in subjects without clinical cardiovascular disease (4476 subjects) over a median follow-up period of 6.2 years. RESULTS: The incidence of cardiovascular events correlated with measurements of carotid-artery intima-media thickness. The relative risk of myocardial infarction or stroke increased with intima-media thickness (P<0.001). The relative risk of myocardial infarction or stroke (adjusted for age and sex) for the quintile with the highest thickness as compared with the lowest quintile was 3.87 (95 percent confidence interval, 2.72 to 5.51). The association between cardiovascular events and intima-media thickness remained significant after adjustment for traditional risk factors, showing increasing risks for each quintile of combined intima-media thickness, from the second quintile (relative risk, 1.54; 95 percent confidence interval, 1.04 to 2.28), to the third (relative risk, 1.84; 95 percent confidence interval, 1.26 to 2.67), fourth (relative risk, 2.01; 95 percent confidence interval, 1.38 to 2.91), and fifth (relative risk, 3.15; 95 percent confidence interval, 2.19 to 4.52). The results of separate analyses of myocardial infarction and stroke paralleled those for the combined end point. CONCLUSIONS: Increases in the thickness of the intima and media of the carotid artery, as measured noninvasively by ultrasonography, are directly associated with an increased risk of myocardial infarction and stroke in older adults without a history of cardiovascular disease.

Asymptomatic internal carotid artery stenosis defined by ultrasound and the risk of subsequent stroke in the elderly. The Cardiovascular Health Study.

BACKGROUND AND PURPOSE: We sought in this study to relate carotid ultrasound findings in asymptomatic older adults to the 5-year risk of various cerebrovascular outcomes used in the Asymptomatic Carotid Atherosclerosis Study (ACAS). METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years and older. Analyses of internal carotid artery stenosis defined by multiple different cutoffs of peak systolic velocity, rather than one particular cutoff, were performed in the 5441 participants who underwent carotid ultrasound and lacked a history of transient ischemic attack or stroke. The 5-year risks of 7 cerebrovascular disease outcomes used in ACAS were estimated for each cutoff. RESULTS: Associations with the 5-year risk of outcomes were substantially elevated only at cutoffs with high peak systolic velocities. In this population, the number of people with such high velocities was small. For example, with a cutoff of approximately 2.5 m/s, suggesting a stenosis of >70%, the 5-year risk of an ipsilateral fatal or nonfatal stroke was 5%, and only 0.5% of the group had velocities at least this high. CONCLUSIONS: In a group of older adults likely to participate in a screening program, as evidenced by willingness to participate in CHS, high peak systolic velocities consistent with high-grade carotid stenosis were uncommon and risk of subsequent cerebrovascular disease outcomes was relatively low. These findings do not suggest that similar populations of older adults would benefit from a program using ultrasound to screen for asymptomatic carotid stenosis.

Stress-induced pulse pressure change predicts women's carotid atherosclerosis.

BACKGROUND AND PURPOSE: Individuals who exhibit large increases in blood pressure and heart rate during mental stress may be at risk for accelerated atherosclerosis. This report evaluates the association between stress-induced hemodynamic responses and carotid atherosclerosis in 254 healthy postmenopausal women. METHODS: The magnitude of change in blood pressure and heart rate from rest to public speaking and mirror image tracing, two stressful tasks, was measured. Average intima-media thickness (IMT) and focal plaque in the common carotid artery, bulb, and internal carotid artery were measured with the use of duplex ultrasonography on average 2.3 years later. RESULTS: The average IMT was 0.77 mm, with a range of 0.60 to 1.37; 52.5% had at least one plaque. Correlational analysis showed that greater IMT was associated with greater pulse pressure change during mental stress (r = 0.17, P < 0.01). Statistical adjustments for possible confounders (age, hormone replacement therapy use, resting pulse pressure, smoking status, and triglyceride levels) did not alter the results. The plaque index was associated with greater pulse pressure change during the mirror image tracing task (odds ratio = 1.47, P = 0.01) for women with a plaque score of > or = 2 versus 1 or 0, adjusted for possible confounders. CONCLUSIONS: Mental stress-induced pulse pressure changes may influence the development of early atherosclerosis in the carotid artery of women. Widening of pulse pressure during stress, as well as at rest, may be a marker of compromised compliance in the vessel wall.

Does the association of risk factors and atherosclerosis change with age? An analysis of the combined ARIC and CHS cohorts. The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) investigators.

INTRODUCTION: A decrease in the estimated relative risk of cerebrovascular and cardiovascular diseases associated with known disease risk factors has been observed among elderly cohorts, perhaps suggesting that continued risk factor management in the elderly may not be as efficacious as with younger age groups. In this paper, the differential magnitude of the association of risk factors with atherosclerosis across the age spectrum from 45 years to older than 75 years is presented. METHODS: Subclinical atherosclerosis as measured by carotid ultrasonography and risk factor prevalence were assessed using similar methods among participants aged 45 to 64 years in the Atherosclerosis Risk in Communities (ARIC) study and among participants 65 years and older in the Cardiovascular Health Study (CHS). Pooling these two cohorts provided data on the relationship of risk factors and atherosclerosis on nearly 19,000 participants over a broad age range. Regression analyses were used to assess the consistency of the magnitude of the association of risk factors with atherosclerosis across the age spectrum separately for black and white participants in cross-sectional analyses. RESULTS: As expected, each of the risk factors was globally (across all ages) associated with increased atherosclerosis. However, the magnitude of the association did not differ across the age spectrum for hypertension, low density lipoprotein cholesterol (LDL-c), fibrinogen, or body mass index (BMI). For whites, there was a significantly greater impact of smoking and HDL-C among older age strata but a smaller impact of diabetes. For black women, the impact of HDL-C decreased among the older age strata. CONCLUSIONS: These data suggest that most risk factors continue to be associated with increased atherosclerosis at older ages, possibly suggesting a continued value in investigation of strategies to reduce atherosclerosis by controlling risk factors at older ages.

Prevalence and determinants of carotid atherosclerosis in healthy postmenopausal women.

BACKGROUND AND PURPOSE: Subclinical atherosclerosis in the carotid arteries can be assessed noninvasively with B-mode ultrasound. Few studies have included enough younger postmenopausal women to examine risk factors specific to this group that were related to subclinical carotid atherosclerosis. METHODS: A subgroup of 200 participants of the Healthy Women Study underwent B-mode ultrasound of the carotid arteries. Intima-media thickness (IMT) and focal plaque were assessed in each carotid artery. Data regarding risk factors, including blood pressure parameters, lipid values, body mass index, smoking history, and hormone status, were collected at three separate time points (before menopause, 1 year after menopause, and 5 or 8 years after menopause). RESULTS: The mean IMT was 0.76+/-0.11 mm, and 50% of the population had at least one focal plaque. Smoking had the strongest association with the presence of plaque. Women who smoked at the time of the ultrasound evaluation had five times the odds of having at least one focal plaque compared with women who had never smoked (95% confidence interval, 2.0 to 13.0; P < .01). After we controlled for age and years after menopause, premenopausal values of pulse pressure (P < or = .05), LDL cholesterol (P < or = .05), and a history of smoking (P < or = .01) were independently predictive of plaque. Premenopausal values of triglycerides, pulse pressure, and ever smoking were independently related to average IMT after we controlled for age and years after menopause. CONCLUSIONS: This study has provided valuable information about the prevalence of carotid atherosclerosis and the risk factors related to carotid atherosclerosis in a group of healthy postmenopausal women.

Risk factors for abdominal aortic aneurysms in older adults enrolled in The Cardiovascular Health Study.

B-mode ultrasound examinations of the abdominal aorta were performed from 1990 to 1992 to evaluate the prevalence of abdominal aortic aneurysm (AAA) in a subgroup of the Pittsburgh cohort (656 participants, aged 65 to 90 years) of the Cardiovascular Health Study (CHS). In this pilot study, we evaluated various definitions of aneurysm and the reproducibility of the measurements. In year 5 (1992 to 1993) of the CHS, the entire cohort (4741 participants) was examined. AAA was defined as an infrarenal aortic diameter of > or= 3.0 cm, or a ratio of infrarenal to suprarenal diameter of > or= 1.2, or a history of AAA repair. For the entire CHS cohort, prevalence of aneurysms was 9.5% (451/4741) overall, with a prevalence among men of 14.2% (278/1956) and prevalence among women of 6.2% (173/2785). Variables significantly related to AAA were older age; male sex; history of angina, coronary heart disease, and myocardial infarction; lower ankle-arm blood pressure ratio; higher maximum carotid stenosis; greater intima-media thickness of the internal carotid artery; higher creatinine; lower HDL levels and higher LDL levels; and cigarette smoking. The study has documented the strong association of cardiovascular risk factors and measures of clinical and subclinical atherosclerosis and cardiovascular disease and prevalence of aneurysms. We used a definition that is more sensitive than previously reported (diameter or ratio), which allowed the detection of smaller aneurysms and possibly those at an earlier stage of development. Follow-up of this cohort may lead to new criteria for determining the risk factors for progression of aneurysms.

Carotid atherosclerosis in women with polycystic ovary syndrome: initial results from a case-control study.

OBJECTIVE: Our purpose was to determine whether women with polycystic ovary syndrome have greater subclinical atherosclerosis as measured by carotid artery ultrasonography. STUDY DESIGN: Sixteen premenopausal women > or = 40 years old with a history of clinical polycystic ovary syndrome and a current total testosterone concentration > or = 2.0 nmol/L and 16 age-matched (+/- 5 years) cycling women underwent carotid scanning. Intima-media thickness and plaque were compared between cases and controls, as were risk factors for atherosclerosis including body mass index and fasting insulin and lipid levels. Statistical analysis included t tests, Fisher's exact test, and multiple linear regression. RESULTS: Mean +/- SE intima-media thickness was found to be significantly greater for cases with polycystic ovary syndrome (0.680 +/- 0.019 mm) than for controls (0.630 +/- 0.012 mm) (t = 2.31, p = 0.035). Five cases (31.3%) and two controls (12.5%) had ultrasonographic evidence of plaque (not significant). Univariate regressions of intima-media thickness yielded significant coefficients for insulin, total cholesterol, low-density lipoprotein cholesterol and body mass index. When either total cholesterol or low-density lipoprotein were included in the model simultaneously with polycystic ovary syndrome, each retained significance. This was not true for insulin and body mass index, however, suggesting that these factors covaried with polycystic ovary syndrome in a dimension affecting intima-media thickness. CONCLUSIONS: In spite of a major limitation of small sample size, these data suggest that women with polycystic ovary syndrome have an increased risk of subclinical atherosclerosis in their 40s.

A micro carbon electrode for nitric oxide monitoring.

A nitric oxide (NO) probe, consisting of a micro carbon fiber working electrode, 10 microns diameter, a platinum counter electrode, and a silver/silver chloride (Ag/AgCl) reference electrode, has been developed. The carbon fiber working electrode is covered with a Nafion cation exchange membrane. Using differential pulse voltammetry (DPV), we found the NO to N2O reduction current peak at approximately -1.35 V versus Ag/AgCl. This has been reported by others. The DPV current outputs are linearly related to dissolved NO concentrations [NO] in the 2-10 microM range. Catecholamines were found not to interfere with the reduction signal. The Nafion membrane also prevents interference by NO2-, NO3-, and amino acids at normal physiologic pH (pH 7.4). The effects of O2 are accounted for through sampling and subtracting background currents from the peak current. To increase sensitivity and shorten response time, a method of integrated pulse amperometry (IPA) was used for the study. The IPA charge outputs (delta C) are linear to the dissolved [NO] in the 50-350 nM range. The carbon fiber electrode has the potential of being miniaturized to a smaller electrode, allowing detection of NO released from the subendothelial space.

A microchip glucose sensor.

A major problem in development of a glucose sensor for use in an implantable artificial pancreas is the lack of reproducibility in signals from sensor to sensor. Each glucose sensor fabricated with currently used methods has a unique response to varying levels of glucose concentration and thus needs to be individually calibrated before use. We have adapted microchip manufacturing techniques for the fabrication of electrochemically based glucose sensors with standardized and reproducible function. Scanning electron microscopic study of the resulting electrode surfaces shows them to be smooth and featureless at all levels of magnification. X-ray diffraction analysis of the electrodes indicates preferential exposure of the [1,1,1] crystal interface. Cyclic voltammetry evaluation of initial sensor response to varying glucose concentrations shows excellent sensor to sensor reproducibility for all sensors made with the same underlayment. Sensors made with titanium underlayment appear to be more differentiated and thus more sensitive to variations in glucose concentration than are sensors with chromium underlayment. Although the initial response of microchip glucose sensors appears to be standardized and reproducible, additional development of an appropriate electrical insulation material is required before long-term study of signal stability is feasible.

A nitric oxide sensor using reduction current.

Nitric oxide (NO) has a wide range of biologic activity. Methods commonly used for the detection of biologically derived NO are indirect and measure only the amount of NO released during an interval of time. An electrochemical method available is capable of being direct and continuous but is subject to interference. The recent explosion of scientific research into NO activity requires better methods of NO detection. This article reports a new NO electrochemical sensing method and sensor design. The tip of the sensor is covered with a hydrophobic membrane and contains an internal electrolyte. Platinum is used for the working and counter electrodes and silver/silver bromide (Ag/AgBr) for the reference electrode. The components of the internal electrolyte are potassium bromide and sulfuric acid. The NO that diffuses to the working electrode is first oxidized to NO+; the NO+ is reduced to NO; and the reduction current is determined. An integrated pulsed amperometric method is used to achieve the redox of NO and the measurement and integration of the reduction current. The results show that the NO sensor is sensitive and has a rapid response and less interference.

Zeolitic ammonium ion exchange for portable hemodialysis dialysate regeneration.

Ammonia removal from a recirculating dialysate stream is a major challenge in developing a truly portable, regenerable hemodialysis system. Three zeolites, type F, type W, and clinoptilolite, were found to have good ammonia ion exchange capacity with linear equilibrium ion exchange coefficients of 0.908, 0.488, and 0.075 L/g, respectively. The linear equilibrium ion exchange coefficient relates dialysate ammonia concentration (mumol/L) to the amount of ammonia absorbed by zeolite (mumol/g) at equilibrium. Ammonia uptake by zeolite powders was fast, with equilibrium reached within 15 sec. Zeolite ammonia ion exchange and regeneration through multiple cycles was studied using an ion exchange column containing clinoptilolite pellets. Zeolite ion exchange capability was regenerated by flushing the column with 2 mol/L sodium chloride after an ion exchange run. The column maintained ammonia ion exchange capacity through six ion exchange/regeneration cycles, demonstrating multiple dialysis use possibilities. Atomic absorption spectroscopy of the column effluent showed no detectible (< 1 part per million) Si or Al leached from the zeolite.

The association of waist/hip ratio with diabetes complications in an adult IDDM population.

Cross-sectional data from the Epidemiology of Diabetes Complications Study were used to examine the relationships between waist to hip circumference ratio (WHR) and the presence of diabetes complications in IDDM adults ages 18-45 years (N = 586). Significantly higher WHRs were observed among both genders with proliferative retinopathy or peripheral vascular disease and only among males with either neuropathy or nephropathy compared to those free of these complications. Logistic regression to determine the strength of association between WHR and each complication demonstrated that although WHR was significantly related to each complication (except nephropathy among females), WHR was only independently related to neuropathy in males and PVD in females in the final model when hypertension, LDL- and HDL-cholesterol and fibrinogen were included. These findings suggest that WHR acts as a marker of risk for diabetes complications mainly through an influence on other complication risk factors.

Causes, implications, and treatment of systolic hypertension.

Mild hypertension is currently defined as systolic blood pressure between 140 and 160 mm Hg. The prevalence of systolic hypertension (including this mild category) in individuals 65 and older is 21% for men and 23% for women. Risk factors include obesity, excessive sodium and alcohol consumption, and possibly calcium and bone metabolism. Determinants of arterial wall rigidity and subsequent increase in pulse-wave velocity are also clearly factors. Much of the associated disease occurs in individuals with systolic pressures between 140 and 159 mm Hg. A particularly high-risk group appears to be those with an elevated systolic blood pressure and a low diastolic blood pressure. Systolic hypertension has now been found to be related to the progression of peripheral atherosclerosis, with lower progression rates among treated individuals. In addition, the beneficial effects of antihypertensive therapy have been found to be strongest among individuals with evidence of subclinical peripheral atherosclerosis. The high prevalence of mild systolic hypertension and its clear association with atherosclerotic disease suggests that older individuals with early systolic hypertension should be identified and treated. Clinical trials to test the efficacy of such treatment should be a high priority, perhaps in subgroups with early subclinical disease.

Interference of glucose sensing by amino acids.

Interference by membrane permeable substances on nonspecific electrodes is a major problem in glucose sensing. Alanine, lysine, phenylalanine, and cystine were chosen for study to gain insight into this problem. These compounds represent the classes of mono-amino aliphatic, di-amino aliphatic, aromatic, and sulfur containing amino acids, respectively. Cyclic voltammetry experiments were performed using a Pt electrode (1.77 mm2). The reductive current of glucose at -0.750 V versus Ag/AgCl was measured with increasing concentrations of interfering substances in Krebs-Ringer phosphate buffer (pH 7.4) at 37 degrees C. Experimental results have shown that these amino acids have an inhibitory effect on the glucose signal. An important finding was that the interferences from phenylalanine and cystine were more pronounced than those of lysine and alanine. An initial drop in the glucose signal was seen at less than 2.0 mg/dl of alanine or lysine and at less than 0.5 mg/dl of phenylalanine or cystine. Additional increase in the concentrations of interfering substance did not cause further appreciable signal reduction. The results confirm that glucose sensing using a non-specific electrode is possible in fluids containing interfering substances such as amino acids.

Blood pressure treatment slows the progression of carotid stenosis in patients with isolated systolic hypertension.

BACKGROUND AND PURPOSE: The Systolic Hypertension in the Elderly Program (SHEP) was a randomized trial testing the efficacy of treating systolic hypertension in older adults. A significant reduction in stroke risk was observed among participants assigned to active treatment. Serial carotid duplex scans were performed on 129 participants at the University of Pittsburgh center, and rates of progression and regression of carotid stenosis were observed. METHODS: Changes in blood flow velocity ratios were used to detect progression because they can be reliably measured and their relation to degree of residual lumen is known. Progression required the development of a 40% to 50% diameter stenosis when stenosis was not initially present or, if already present, further reduction in the lumen diameter. Regression required the absence of a 40% to 50% diameter stenosis when stenosis was initially present or a stenosis significantly less severe than that initially seen. RESULTS: Progression occurred in 22% (28/129) of participants and regression in 16% (8/49). Progression of carotid stenosis occurred more often among participants randomized to placebo as compared with active treatment (31% versus 14%, P = .020). All eight patients exhibiting-regression were randomized to active treatment. In multivariate analysis, participants assigned to placebo had 4.3 times greater odds of progressing than participants assigned to active treatment. Other factors significantly related to progression were higher degree of plaque at baseline, low high-density lipoprotein-3, high lipoprotein(a), and younger age. CONCLUSIONS: Treating systolic hypertension appears to slow progression of carotid stenosis. Similar effects occurring in the intracranial vessels may be one reason for the substantial decrease in stroke among SHEP participants assigned to active treatment.

Segmental arterial disease in the lower extremities: correlates of disease and relationship to mortality.

The purpose of this study was to identify the correlates of disease and mortality risk associated with the presence of stenosis in the major arterial segments of the lower limb in men and women evaluated in a peripheral vascular laboratory. A total of 326 men and 249 women had unisegmental stenosis; 312 men and 275 women had multisegmental disease; 132 men and 111 women had no apparent disease. Multivariate analysis indicated that current smoking and elevated systolic blood pressure were the key risk factors associated with isolated aortoiliac and femoropopliteal arterial disease in both men and women. A history of diabetes was significantly associated with tibioperoneal disease in men while elevated systolic blood pressure was the major correlate of distal disease in women in this patient population. The relative risk of mortality was elevated 2- to 7-fold in men and women with multi- and unisegmental disease involving the aortoiliac and femoropopliteal segments; presence of tibioperoneal disease did not significantly increase mortality relative to those who were free of disease. These results suggest that the etiology and mortality risk associated with atherosclerosis in the lower extremity may vary with the anatomic site and/or severity of the lesion.

Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group.

BACKGROUND: Peripheral arterial disease measured noninvasively by the ankle-arm index (AAI) is common in older adults, largely asymptomatic, and associated with clinically manifest cardiovascular disease (CVD). The criteria for an abnormal AAI have varied in previous studies. To determine whether there is an inverse dose-response relation between the AAI and clinical CVD, subclinical disease, and risk factors, we examined the relation of the AAI to cardiovascular risk factors, other noninvasive measures of subclinical atherosclerosis using carotid ultrasound, echocardiography and electrocardiography, and clinical CVD. METHODS AND RESULTS: The AAI was measured in 5084 participants > or = 65 years old at the baseline examination of the Cardiovascular Health Study. All subjects had detailed assessment of prevalent CVD, measures of cardiovascular risk factors, and noninvasive measures of disease. Participants were stratified by baseline clinical CVD status and AAI (< 0.8, > or = 0.8 to < 0.9, > or = 0.9 to < 1.0, > or = 1.0 to < 1.5). Analyses tested for a dose-response relation of the AAI with clinical CVD, risk factors, and subclinical disease. The cumulative frequency of a low AAI was 7.4% of participants < 0.8, 12.4% < 0.9, and 23.6% < 1.0. participants with an AAI < 0.8 were more than twice as likely as those with an AAI of 1.0 to 1.5 to have a history of myocardial infarction, angina, congestive heart failure, stroke, or transient ischemic attack (all P < .01). In participants free of clinical CVD at baseline, the AAI was inversely related to history of hypertension, history of diabetes, and smoking, as well as systolic blood pressure, serum creatinine, fasting glucose, fasting insulin, measures of pulmonary function, and fibrinogen level (all P < .01). Risk factor associations with the AAI were similar in men and women free of CVD except for serum total and low-density lipoprotein cholesterol, which were inversely associated with AAI level only in women. Risk factors associated with an AAI of < 1.0 in multivariate analysis included smoking (odds ratio [OR], 2.55), history of diabetes (OR, 3.84), increasing age (OR, 1.54), and nonwhite race (OR, 2.36). In the 3372 participants free of clinical CVD, other noninvasive measures of subclinical CVD, including carotid stenosis by duplex scanning, segmental wall motion abnormalities by echocardiogram, and major ECG abnormalities were inversely related to the AAI (all P < .01). CONCLUSIONS: There was an inverse dose-response relation of the AAI with CVD risk factors and subclinical and clinical CVD among older adults. The lower the AAI, the greater the increase in CVD risk; however, even those with modest, asymptomatic reductions in the AAI (0.8 to 1.0) appear to be at increased risk of CVD.

Sonographic evaluation of carotid artery atherosclerosis in the elderly: relationship of disease severity to stroke and transient ischemic attack.

Doppler and real-time ultrasound (US) were performed to evaluate the extent of atherosclerotic changes in the carotid artery and to assess their relationship to prevalent cerebrovascular disease. Real-time US scans and Doppler measurements of the carotid arteries were analyzed in 5,201 subjects aged 65 years or older. Severity of atherosclerotic lesions was associated with increased frequencies of hyperechoic, irregular, and heterogeneous textured lesions (P < .0001). The severity of internal carotid artery stenosis was associated with thickening of the intima-media layer of the common carotid artery wall (r = .37, P < .0001). A history of stroke and transient ischemic attack (TIA) was more likely when hyperechoic, heterogeneous, and irregular lesions were seen in the carotid artery. Internal carotid artery stenosis correlated better with prevalent stroke and TIA than did sonographic descriptions of plaque texture. However, the prevalence of hyperechoic, heterogeneous, and irregular lesions increased as the degree of internal carotid stenosis increased. On real-time images alone, the average of the internal carotid artery maximal wall thickness is the sonographic measure of atherosclerosis that enables the best prediction of prevalent stroke and TIA.

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.