Ambulatory blood pressure monitoring phenotypes among individuals with and without diabetes taking antihypertensive medication: the Jackson Heart Study.

Ambulatory blood pressure monitoring (ABPM) can detect phenotypes associated with increased cardiovascular disease (CVD) risk. Diabetes is associated with increased CVD risk but few data are available documenting whether blood pressure (BP) phenotypes, detected by ABPM, differ between individuals with versus without diabetes. We conducted a cross-sectional analysis of 567 participants in the Jackson Heart Study, a population-based study of African Americans, taking antihypertensive medication to evaluate the association between diabetes and ABPM phenotypes. Two clinic BP measurements were taken at baseline following a standardized protocol. ABPM was performed for 24 h following the clinic visit. ABPM phenotypes included daytime, sustained, nocturnal and isolated nocturnal hypertension, a non-dipping BP pattern, and white coat, masked and masked isolated nocturnal hypertension. Diabetes was defined as fasting glucose ⩾126 mg dl-1, haemoglobin A1c ⩾6.5% (48 mmol mol-1) or use of insulin or oral hypoglycaemic medications. Of the included participants (mean age 62.3 years, 71.8% female), 196 (34.6%) had diabetes. After multivariable adjustment, participants with diabetes were more likely to have daytime hypertension (prevalence ratio (PR): 1.32; 95% confidence interval (CI): 1.09-1.60), masked hypertension (PR: 1.46; 95% CI: 1.11-1.93) and masked isolated nocturnal hypertension (PR: 1.39; 95% CI: 1.02-1.89). Although nocturnal hypertension was more common among participants with versus without diabetes, this association was not present after adjustment for daytime systolic BP. Diabetes was not associated with the other ABPM phenotypes investigated. This study highlights the high prevalence of ABPM phenotypes among individuals with diabetes taking antihypertensive medication.

Physical activity and physiological cardiac remodelling in a community setting: the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVE: To evaluate the association of physical activity with left ventricular structure and function in the general population in a community setting. DESIGN: Cross-sectional study. SETTING: The Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of subclinical atherosclerosis. PARTICIPANTS: A multiethnic sample of 4992 participants (aged 45-84 years; 52% female) free of clinically apparent cardiovascular disease. INTERVENTIONS: Physical activity induces beneficial physiological cardiac remodelling in a cross-sectional study of non-athlete individuals. MAIN OUTCOME MEASURES: Left ventricular mass, volumes and function were assessed by cardiac magnetic resonance imaging. Physical activity, defined as intentional exercise and total moderate and vigorous physical activity, was assessed by a standard semiquantitative questionnaire. RESULTS: Left ventricular mass and end-diastolic volume were positively associated with physical activity (eg, 1.4 g/m(2) (women) and 3.1 g/m(2) (men) greater left ventricular mass in the highest category of intentional exercise compared with individuals reporting no intentional exercise; p = 0.05 and p<0.001, respectively). Relationships were non-linear, with stronger positive associations at lower levels of physical activity (test for non-linearity; p = 0.02 and p = 0.03, respectively). Cardiac output and ejection fraction were unchanged with increased physical activity levels. Resting heart rate was lower in women and men with higher physical activity levels (eg, -2.6 beats/minute lower resting heart rate in the highest category of intentional exercise compared with individuals reporting no intentional exercise; p<0.001). CONCLUSIONS: In a community-based population free of clinically apparent cardiovascular disease, higher physical activity levels were associated with proportionally greater left ventricular mass and end-diastolic volume and lower resting heart rate.

Serological evidence of infections and Type 2 diabetes: the MultiEthnic Study of Atherosclerosis.

AIMS: Prospective studies have identified chronic inflammation as a risk factor for Type 2 diabetes. However, it is not known whether infection by specific pathogens or having a greater 'pathogen burden' is associated with diabetes. The aim of this study was to examine the cross-sectional relation of seropositivity to five pathogens (Chlamydia pneumoniae, cytomegalovirus, Helicobacter pylori, hepatitis A virus, herpes simplex virus) and prevalent diabetes. METHODS: Baseline data from a random sample of MultiEthnic Study of Atherosclerosis (MESA) participants (n = 1000; age 45-84 years) were used. Diabetes was defined by American Diabetes Association 2003 criteria, and 'pathogen burden' by the number of pathogens (0-5) for which an individual was seropositive. Logistic regression was used to test differences in diabetes prevalence by seropositivity. Linear regression was used to explore associations between pathogen seropositivity and the inflammation markers C-reactive protein, interleukin-6 and fibrinogen. RESULTS: Diabetes prevalence was 12.7%, whereas seropositivity for C. pnuemoniae was 76%, cytomegalovirus 77%, H. pylori 45%, hepatitis A 58% and herpes simplex virus 85%. Seventy-two percent were seropositive for three or more pathogens. In crude analyses, the prevalence of diabetes was higher among those with a pathogen burden of three or more, and with seropositivity to cytomegalovirus, H. pylori, hepatitis A and herpes simplex virus. After adjustment for demographic covariates (particularly race), all associations became non-significant. Pathogen seropositivity was also not related to inflammation marker levels. CONCLUSIONS: Following demographic adjustments, no associations were observed between infection by several pathogens and diabetes status, suggesting no aetiological role for them in the occurrence of diabetes.

HbA 1c as a risk factor for heart failure in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: Heart failure (HF) incidence in diabetes in both the presence and absence of CHD is rising. Prospective population-based studies can help describe the relationship between HbA(1c), a measure of glycaemia control, and HF risk. METHODS: We studied the incidence of HF hospitalisation or death among 1,827 participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes and no evidence of HF at baseline. Cox proportional hazard models included age, sex, race, education, health insurance status, alcohol consumption, BMI and WHR, and major CHD risk factors (BP level and medications, LDL- and HDL-cholesterol levels, and smoking). RESULTS: In this population of persons with diabetes, crude HF incidence rates per 1,000 person-years were lower in the absence of CHD (incidence rate 15.5 for CHD-negative vs 56.4 for CHD-positive, p<0.001). The adjusted HR of HF for each 1% higher HbA(1c) was 1.17 (95% CI 1.11-1.25) for the non-CHD group and 1.20 (95% CI 1.04-1.40) for the CHD group. When the analysis was limited to HF cases which occurred in the absence of prevalent or incident CHD (during follow-up) the adjusted HR remained 1.20 (95% CI 1.11-1.29). CONCLUSIONS/INTERPRETATIONS: These data suggest HbA(1c) is an independent risk factor for incident HF in persons with diabetes with and without CHD. Long-term clinical trials of tight glycaemic control should quantify the impact of different treatment regimens on HF risk reduction.

Diabetes and the risk of infection-related mortality in the U.S.

OBJECTIVE: To determine whether diabetes predicts infection-related mortality and to clarify the extent to which this relationship is mediated by comorbid conditions that may themselves increase risk of infection. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study using the Second National Health and Nutrition Examination Survey Mortality Study of 9,208 adults aged 30-74 years in 1976-1980. We defined demographic variables, diabetes, cardiovascular disease (CVD), and smoking by self-report; BMI, blood pressure, and serum cholesterol from baseline examination; and cause-specific mortality from death certificates. RESULTS: Over 12-16 years of follow-up, 36 infection-related deaths occurred among 533 adults with diabetes vs. 265 deaths in 8,675 adults without diabetes (4.7 vs. 1.5 per 1,000 person-years, P < 0.001). Diabetes (RR 2.0, 95% CI 1.2-3.2) and congestive heart failure (2.8, 1.6-5.1) were independent predictors of infection-related mortality after simultaneous adjustment for age, sex, race, poverty status, smoking, BMI, and hypertension. After subdividing infection-related deaths into those with (n = 145) and without (n = 156) concurrent cardiovascular diagnoses at the time of death, diabetic adults were at risk for infection-related death with CVD (3.0, 1.8-5.0) but not without CVD (1.0, 0.5-2.2). CONCLUSIONS: These nationally representative data suggest that diabetic adults are at greater risk for infection-related mortality, and the excess risk may be mediated by CVD.

Impaired posthypoxic relaxation in single cardiac myocytes: role of intracellular pH and inorganic phosphate.

OBJECTIVE: The aim was to examine the effects of alterations in intracellular pH and inorganic phosphate concentration (known to influence myofilament kinetics and to change rapidly during hypoxia) on cell contraction, relaxation, and the Ca2+ transient in normoxic and hypoxic myocytes. METHODS: Single adult rat ventricular myocytes were electrically stimulated (0.2 Hz) and cell length (photodiode array), intracellular Ca2+ (indo-1 fluorescence), or intracellular pH (SNARF-1 fluorescence) measured. Hypoxia was induced in a special open chamber in which a laminar layer of argon prevented the back diffusion of atmospheric oxygen. RESULTS: Electrically stimulated contraction was preserved during exposure to hypoxia. At reoxygenation 10 minutes later the time from the stimulus to the peak of contraction (TPK) increased by 30(SEM 9)% and the time from the peak of contraction to 50% recovery of cell length (RT50) increased by 59(13)% relative to prehypoxic values (n = 8). These changes were not accompanied by a change in the kinetics of the Ca2+ transient. pHi fell from a baseline of 7.33(0.04) to 7.25(0.03) during hypoxia and then overshot to 7.44(0.03) at reoxygenation (n = 5). Since an intracellular alkalosis can slow myofilament relaxation, proton extrusion routes were blocked to examine posthypoxic relaxation in the absence of an alkalosis. Despite inhibition of the pHi overshoot, posthypoxic relaxation remained impaired. Intracellular inorganic phosphate levels were manipulated in two protocols (2-deoxyglucose to "trap" phosphate and Tris(hydroxymethyl)-aminomethane to buffer phosphate) and both TPK and RT50 increased in normoxic cells. Having established that these two interventions, which would be expected to decrease intracellular inorganic phosphate, result in a slowing of relaxation, myocytes were first phosphate loaded (exposed to 5.0 mM phosphate) and then made hypoxic and reoxygenated after 10 min to blunt the expected fall in phosphate accompanying reoxygenation. This led to a reduction in the slowing of contraction and relaxation following reoxygenation [TPK increased by 7(5)% and RT50 by 17(9)%, n = 8; p < 0.05 v cells studied in control buffer]. CONCLUSIONS: Impaired posthypoxic relaxation is not the result of changes in pHi but is attenuated by phosphate loading of cells and may be due to a rapid decrease in intracellular phosphate accompanying the resynthesis of high energy phosphates at reoxygenation.