Robert C. Kaplan

T Cell Activation and Senescence Predict Subclinical Carotid Artery Disease in HIV-Infected Women

Background. Individuals infected with human immunodeficiency virus (HIV) have increased risk of cardiovascular events. It is unknown whether T cell activation and senescence, 2 immunologic sequelae of HIV infection, are associated with vascular disease among HIV-infected adults. Methods. T cell phenotyping and carotid ultrasound were assessed among 115 HIV-infected women and 43 age- and race/ethnicity-matched HIV-uninfected controls participating in the Womens Interagency HIV Study. Multivariate analyses were used to assess the association of T cell activation (CD38+HLA-DR+) and senescence (CD28−CD57+) with subclinical carotid artery disease. Results. Compared with HIV-uninfected women, frequencies of CD4+CD38+HLA-DR+, CD8+CD38+HLA-DR+, and CD8+CD28−CD57+ T cells were higher among HIV-infected women, including those who achieved viral suppression while receiving antiretroviral treatment. Among HIV-infected women, adjusted for age, antiretroviral medications, and viral load, higher frequencies of activated CD4+ and CD8+ T cells and immunosenescent CD8+ T cells were associated with increased prevalence of carotid artery lesions (prevalence ratiolesions associated with activated CD4+ T cells, 1.6 per SD [95% confidence interval {CI}, 1.1–2.2]; P = .02; prevalence ratiolesions associated with activated CD8+ T cells, 2.0 per SD [95% CI, 1.2–3.3]; P < .01; prevalence ratiolesions associated with senescent CD8+ T cells, 1.9 per SD [95% CI, 1.1–3.1]; P = .01). Conclusions. HIV-associated T cell changes are associated with subclinical carotid artery abnormalities, which may be observed even among those patients achieving viral suppression with effective antiretroviral therapy.

Ten-Year Predicted Coronary Heart Disease Risk in HIV-Infected Men and Women

BACKGROUND Highly active antiretroviral therapy (HAART), in addition to traditional vascular risk factors, may affect coronary heart disease (CHD) risk in individuals with human immunodeficiency virus (HIV) infection. METHODS Among HIV-infected (931 men and 1455 women) and HIV-uninfected (1099 men and 576 women) adults, the predicted risk of CHD was estimated on the basis of age, sex, lipid and blood pressure levels, the presence of diabetes, and smoking status. RESULTS Among HIV-infected men, 2% had moderate predicted risk of CHD (10-year CHD risk, 15%-25%), and 17% had high predicted risk (10-year CHD risk of > or = 25% or diabetes). Among HIV-infected women, 2% had moderate predicted CHD risk, and 12% had high predicted CHD risk. Compared with users of protease inhibitor-based HAART, the adjusted odds ratio (OR) for moderate-to-high risk of CHD was significantly lower among HAART-naive individuals (OR, 0.57; 95% confidence interval [CI], 0.36-0.89). Users of HAART that was not protease inhibitor based (OR, 0.74; 95% CI, 0.53-1.01) and former HAART users (OR, 0.68; 95% CI, 0.46-1.03) were also less likely than users of protease inhibitor-based HAART to have moderate-to-high CHD risk, although 95% CIs overlapped the null. Low income was associated with increased likelihood of moderate-to-high CHD risk (for annual income <

The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes.

10,000 vs. >

Exercise, body mass index, caloric intake, and cardiovascular mortality

40,000: OR, 2.32; 95% CI, 1.51-3.56 ). Elevated body mass index (calculated as weight in kilograms divided by the square of height in meters) predicted increased likelihood of moderate-to-high CHD risk (for BMI of 18.5-24.9 vs. BMI of 25-30: OR, 1.41 [95% CI, 1.03-1.93]; for BMI of 18.5-24.9 vs. BMI > or = 30: OR, 1.79 [95% CI, 1.25-2.56]). CONCLUSIONS Among HIV-infected adults, in addition to antiretroviral drug exposures, being overweight and having a low income level were associated with increased predicted CHD risk. This suggests a need to target HIV-infected men and women with these characteristics for vascular risk factor screening.

Predictors of subsequent coronary events, stroke, and death among survivors of first hospitalized myocardial infarction

This review addresses the possible role of the insulin‐like growth factor (IGF)‐axis in normal glucose homoeostasis and in the etiopathogenesis of type 2 diabetes. IGF‐I, a peptide hormone, shares amino acid sequence homology with insulin and has insulin‐like activity; most notably, the promotion of glucose uptake by peripheral tissues. Type 2 diabetes as well as pre‐diabetic states, including impaired fasting glucose and impaired glucose tolerance, are associated cross‐sectionally with altered circulating levels of IGF‐I and its binding proteins (IGFBPs). Administration of recombinant human IGF‐I has been reported to improve insulin sensitivity in healthy individuals as well as in patients with insulin resistance and type 2 diabetes. Further, IGF‐I may have beneficial effects on systemic inflammation, a risk factor for type 2 diabetes, and on pancreatic β‐cell mass and function. There is considerable inter‐individual heterogeneity in endogenous levels of IGF‐I and its binding proteins; however, the relationship between these variations and the risk of developing type 2 diabetes has not been extensively investigated. Large prospective studies are required to evaluate this association. Copyright

Blood pressure control and risk of incident atrial fibrillation

BACKGROUND The association of physical inactivity and elevated body mass index (BMI) with cardiovascular disease (CVD) risk is well established. The relationship of dietary caloric intake and CVD risk is less certain. METHODS The epidemiologic follow-up of the First National Health and Nutrition Examination Survey (1971-1992) was examined to determine the relationship of caloric intake, BMI, and physical activity to CVD mortality. Of 14,407 participants, 9790 subjects aged 25 to 74 years met inclusion criteria. The CVD mortality rate was the outcome. RESULTS During the 17 years of follow-up, there were 3183 deaths, 1531 of which were due to CVD (9.11/1000 person-years). People with relatively less physical activity, lower caloric intake, and who were overweight (BMI 25 to 29.9 kg/m(2)) and obese (BMI > or =30 kg/m(2)) had a less favorable baseline CVD risk profile than did those who were more active and of normal weight and had greater caloric intake. Age- and race/ethnicity-adjusted CVD mortality rates were highest among those with the least physical activity and lowest caloric intake, and who were overweight or obese. Moreover, subjects of normal weight who exercised most were more likely to have high caloric intake and lower CVD mortality (5.9 vs 14.7 per 1000 person-years, p =0.01) than subjects who were obese and exercised least. In Cox regression analysis, controlling for relevant CVD risk factors, least physical activity was independently associated with increased CVD mortality (hazard ratio=1.32, 95% confidence interval [CI]=1.13-1.53); and obesity was associated with increased CVD mortality (hazard ratio=1.24, 95% CI=1.06-1.44). Although highest dietary caloric intake was associated with reduced CVD mortality (hazard ratio=0.83, 95% CI=0.74-0.93), after adjusting for physical activity and BMI, there was no significant association of highest caloric intake with CVD mortality (hazard ratio=0.91, 95% CI=0.81-1.01). CONCLUSIONS In this large general population sample, lower levels of physical activity and obesity were independently associated with decreased CVD survival. Moreover, when BMI, physical activity, and other relevant characteristics were taken into account, caloric intake was not related to CVD mortality.

T cell activation predicts carotid artery stiffness among HIV-infected women

We identified predictors of prognosis among n = 2,677 health maintenance organization enrollees 30 to 79 years old who survived a first hospitalized myocardial infarction (MI) during 1986-1996 (mean follow-up 3.4 years). Independent risk factors for reinfarction/fatal coronary heart disease (CHD) (incidence = 49.0/1,000 person-years, 445 events) were age, diabetes, chronic congestive heart failure (CHF), angina, high body mass index (BMI), low diastolic blood pressure (DBP), high serum creatinine, and low/high-density lipoprotein (HDL) cholesterol. Independent risk factors for stroke (incidence = 13.0/1,000 person-years, 124 events) were age, diabetes, CHF, high DBP, and high creatinine. Independent predictors of death (incidence = 44.2/1,000 person-years, 431 events) were age, diabetes, CHF, continued smoking after MI, low DBP, high pulse rate, high creatinine, and low HDL cholesterol, while BMI had a significant U-shaped association with death (elevated risk at low and high BMI). The occurrence of study end points did not differ significantly between men and women after adjustment for other risk factors and use of preventive medical therapies, although men tended to have higher rates of reinfarction/CHD than women among older subjects. In summary, we demonstrated that the major cardiovascular risk factors age, diabetes, CHF, smoking, and dyslipidemia are important prognostic factors in the years after nonfatal MI. Elevated BMI was associated with increased risk of reinfarction/CHD and death and elevated DBP with increased risk of stroke, but we also observed high mortality among those with low BMI and high risk of recurrent coronary disease and death among those with low DBP. Finally, high creatinine was a strong, independent predictor of a variety of adverse outcomes after first MI.

Body mass index and the risk of recurrent coronary events following acute myocardial infarction.

BACKGROUND Atrial fibrillation (AF) is a common arrhythmia that affects more than 2 million people in the United States. We sought to determine whether the risk of incident AF among patients treated for hypertension differs by the degree of blood pressure control. METHODS A population-based, case-control study of 433 patients with verified incident AF and 899 controls was conducted to investigate the relationship between average achieved systolic (SBP) and diastolic (DBP) blood pressure and risk of AF. All patients were members of an integrated health-care delivery system and were pharmacologically treated for hypertension. Medical records were reviewed to confirm the diagnosis of new onset AF and to collect information on medical conditions, health behaviors, and measured blood pressures. Average achieved SBP and DBP were calculated from the three most recent outpatient blood pressure measurements. RESULTS Compared with the reference level of 120-129 mm Hg, for categories of average achieved SBP of <120, 130-139, 140-149, 150-159, 160-169, and > or =170 mm Hg, the odds ratios (ORs; 95% confidence interval (CI)) for incident AF were 1.99 (1.10, 3.62), 1.19 (0.78, 1.81), 1.40 (0.93, 2.09), 2.02 (1.30, 3.15), 2.27 (1.31, 3.93), and 1.84 (0.89, 3.80), respectively. Based on the population attributable fraction, we estimated that, among patients with treated hypertension, 17.2% (95% CI 4.3%, 28.3%) of incident AF was attributable to an average achieved SBP > or =140 mm Hg. CONCLUSION Among patients treated for hypertension, uncontrolled elevated SBP and SBP <120 mm Hg were associated with an increased risk of incident AF.

Cytomegalovirus Immunoglobulin G Antibody Is Associated With Subclinical Carotid Artery Disease Among HIV-Infected Women

OBJECTIVES HIV disease is associated with increased arterial stiffness, which may be related to inflammation provoked by HIV-related immune perturbation. We assessed the association of T cell markers of immune activation and immunosenescence with carotid artery stiffness among HIV-infected women. METHODS Among 114 HIV-infected and 43 HIV-uninfected women, we measured CD4+ and CD8+ T cell populations expressing activation (CD38+HLA-DR+) and senescence (CD28-CD57+) markers. We then related these measures of immune status with parameters of carotid artery stiffness, including decreased distensibility, and increased Youngs elastic modulus, as assessed by B-mode ultrasound. RESULTS HIV infection was associated with increased CD4+ T cell activation, CD8+ T cell activation and CD8+ T cell senescence. Among HIV-infected women, adjusted for age, HIV medications, and vascular risk factors, higher CD4+CD38+HLA-DR+ T cell frequency was associated with decreased carotid artery distensibility (β=-2.00, 95% confidence interval [CI]=-3.86, -0.14, P=0.04) and increased Youngs modulus (β=1.00, 95% CI=0.03, 1.97, P=0.04). These associations were affected little by further adjustment for CD4+ T cell count and viral load. Among HIV-infected women, higher frequencies of immunosenescent T cells, including CD4+CD28-CD57+ and CD8+CD28-CD57+ T cells, were also associated with decreased arterial distensibility. Among HIV-uninfected women, frequencies of activated or senescent T cells were not significantly associated with measures of carotid stiffness. DISCUSSION T cell activation and senescence are associated with arterial stiffness, suggesting that pro-inflammatory populations of T cells may produce functional or structural vascular changes in HIV-infected women.

Risk Factors for Hospitalized Gastrointestinal Bleeding Among Older Persons

Although excess adiposity appears to increase the risk of coronary heart disease in the general population, its importance in patients with established coronary disease is less defined. We evaluated a population-based inception cohort of survivors to hospital discharge following first acute myocardial infarction (AMI) (n = 2,541) to assess the association between body mass index (BMI) and the risk of recurrent coronary events and to explore the mechanisms for this relation. Using Cox proportional-hazards regression, we assessed the risk of recurrent coronary events associated with levels of adiposity as defined by BMI and then investigated potential mechanisms through which adiposity conferred risk by examining how adjustment for diabetes mellitus, systemic hypertension, and dyslipidemia affected the association. Forty-one percent of the cohort were overweight (BMI 25 to 29.9), and 27.8% were obese (BMI > or =30). After adjustment for other risk factors, the risk of recurrent coronary events (n = 418) increased as BMI increased, especially among those who were obese. Using a BMI of 16 to 24.9 as the reference group, for mildly overweight patients (BMI 25 to 27.4), the relative risk (RR) was 0.93 (95% confidence interval [CI] 0.70 to 1.24); it was 1.16 for more severe overweight patients (BMI 27.5 to 29.9; 95% CI 0.87 to 1.55). For patients with class I obesity (BMI 30 to 34.9), the RR was 1.49 (95% CI 1.12 to 1.98), and for class II to III obesity (BMI > or =35), the RR was 1.80 (95% CI 1.30 to 2.48). We estimated that clinical measurements of diabetes, hypertension, and dyslipidemia explained approximately 43% of this risk. Thus, excess adiposity as measured by BMI was associated with an increased risk of recurrent coronary events following AMI, particularly among those who were obese.