O. Dale Williams

Racial Differences in Incident Heart Failure among Young Adults

BACKGROUND The antecedents and epidemiology of heart failure in young adults are poorly understood. METHODS We prospectively assessed the incidence of heart failure over a 20-year period among 5115 blacks and whites of both sexes who were 18 to 30 years of age at baseline. Using Cox models, we examined predictors of hospitalization or death from heart failure. RESULTS Over the course of 20 years, heart failure developed in 27 participants (mean [+/-SD] age at onset, 39+/-6 years), all but 1 of whom were black. The cumulative incidence of heart failure before the age of 50 years was 1.1% (95% confidence interval [CI], 0.6 to 1.7) in black women, 0.9% (95% CI, 0.5 to 1.4) in black men, 0.08% (95% CI, 0.0 to 0.5) in white women, and 0% (95% CI, 0 to 0.4) in white men (P=0.001 for the comparison of black participants and white participants). Among blacks, independent predictors at 18 to 30 years of age of heart failure occurring 15 years, on average, later included higher diastolic blood pressure (hazard ratio per 10.0 mm Hg, 2.1; 95% CI, 1.4 to 3.1), higher body-mass index (the weight in kilograms divided by the square of the height in meters) (hazard ratio per 5.7 units, 1.4; 95% CI, 1.0 to 1.9), lower high-density lipoprotein cholesterol (hazard ratio per 13.3 mg per deciliter [0.34 mmol per liter], 0.6; 95% CI, 0.4 to 1.0), and kidney disease (hazard ratio, 19.8; 95% CI, 4.5 to 87.2). Three quarters of those in whom heart failure subsequently developed had hypertension by the time they were 40 years of age. Depressed systolic function, as assessed on a study echocardiogram when the participants were 23 to 35 years of age, was independently associated with the development of heart failure 10 years, on average, later (hazard ratio for abnormal systolic function, 36.9; 95% CI, 6.9 to 198.3; hazard ratio for borderline systolic function, 3.5; 95% CI, 1.2 to 10.2). Myocardial infarction, drug use, and alcohol use were not associated with the risk of heart failure. CONCLUSIONS Incident heart failure before 50 years of age is substantially more common among blacks than among whites. Hypertension, obesity, and systolic dysfunction that are present before a person is 35 years of age are important antecedents that may be targets for the prevention of heart failure. (ClinicalTrials.gov number, NCT00005130.)

Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels.

Elevated plasma levels of C-reactive protein (CRP), an inflammation-sensitive marker, have emerged as an important predictor of future cardiovascular disease and metabolic abnormalities in apparently healthy men and women. Here, we performed a systematic survey of common nucleotide variation across the genomic region encompassing the CRP gene locus. Of the common single-nucleotide polymorphisms (SNPs) identified, several in the CRP promoter region are strongly associated with CRP levels in a large cohort study of cardiovascular risk in European American and African American young adults. We also demonstrate the functional importance of these SNPs in vitro.

Factors Associated with Mortality in Transplant Patients with Invasive Aspergillosis

BACKGROUND Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. METHODS Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. RESULTS Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; P<.001). Independent poor prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. CONCLUSIONS There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.

Nurse staffing and mortality for Medicare patients with acute myocardial infarction

ContextRecent hospital reductions in registered nurses (RNs) for hospital care raise concerns about patient outcomes. ObjectiveAssess the association of nurse staffing with in-hospital mortality for patients with acute myocardial infarction (AMI). Design, Setting, and Patients.Medical record review data from the 1994–1995 Cooperative Cardiovascular Project were linked with American Hospital Association data for 118,940 fee-for-service Medicare patients hospitalized with AMI. Staffing levels were represented as nurse to patient ratios categorized into quartiles for RNs and for licensed practical nurses (LPNs). Main Outcome Measures.In-hospital mortality. ResultsFrom highest to lowest quartile of RN staffing, in-hospital mortality was 17.8%, 17.4%, 18.5%, and 20.1%, respectively (P < 0.001 for trend). However, from highest to lowest quartile of LPN staffing, mortality was 20.1%, 18.7%, 17.9%, and 17.2%, respectively P < 0.001). After adjustment for patient demographic and clinical characteristics, treatment, and for hospital volume, technology index, and teaching and urban status, patients treated in environments with higher RN staffing were less likely to die in-hospital; odds ratios (95% confidence intervals) of quartiles 4, 3, and 2 versus quartile 1 were 0.91 (0.86–0.97), 0.94 (0.88–1.00), and 0.96 (0.90–1.02), respectively. Conversely, after adjustment, patients treated in environments with higher LPN staffing were more likely to die in-hospital; odds ratios (95% confidence intervals) of quartiles 4, 3, and 2 versus quartile 1 were 1.07 (1.00–1.15), 1.02 (0.96–1.09), and 1.00 (0.94–1.07), respectively. ConclusionsEven after extensive adjustment, higher RN staffing levels were associated with lower mortality. Our findings suggest an important effect of nurse staffing on in-hospital mortality.

Longitudinal association of body mass index with lung function: The CARDIA Study

BackgroundLung function at the end of life depends on its peak and subsequent decline. Because obesity is epidemic in young adulthood, we quantified age-related changes in lung function relative to body mass index (BMI).MethodsThe Coronary Artery Risk Development in Young Adults (CARDIA) study in 1985–86 (year 0) recruited 5,115 black and white men and women, aged 18–30. Spirometry testing was conducted at years 0, 2, 5 and 10. We estimated 10 year change in FVC, FEV1 and FEV1/FVC according to baseline BMI and change in BMI within birth cohorts with initial average ages 20, 24, and 28 years, controlling for race, sex, smoking, asthma, physical activity, and alcohol consumption.Measurements and Main ResultsParticipants with baseline BMI < 21.3 kg/m2 experienced 10 year increases of 71 ml in FVC and 60 ml in FEV1 and neither measure declined through age 38. In contrast, participants with baseline BMI ≥ 26.4 kg/m2 experienced 10 year decreases of 185 ml in FVC and 64 ml in FEV1. FEV1/FVC increased with increasing BMI. Weight gain was also associated with lung function. Those who gained the most weight over 10 years had the largest decrease in FVC, but FVC increased with weight gain in those initially thinnest. In contrast, FEV1 decreased with increasing weight gain in all participants, with maximum decline in obese individuals who gained the most weight during the study.ConclusionAmong healthy young adults, increasing BMI in the initially thin participants was associated with increasing then stable lung function through age 38, but there were substantial lung function losses with higher and increasing fatness. These results suggest that the obesity epidemic threatens the lung health of the general population.

Polymorphisms of the IL1-Receptor Antagonist Gene (IL1RN) Are Associated With Multiple Markers of Systemic Inflammation

Background—Circulating levels of acute phase reactant proteins such as plasma C-reactive protein (CRP) are likely influenced by multiple genes regulating the innate immune response. Methods and Results—We screened a set of 16 inflammation-related genes for association with CRP in a large population-based study of healthy young adults (n=1627). Results were validated in 2 independent studies (n=1208 and n=4310), including a pooled analysis of all 3 studies. In the pooled analysis, the minor allele of IL1RN 1018 (rs4251961) within the gene encoding interleukin (IL)-1 receptor antagonist (IL-1RA) was significantly associated with higher mean plasma log(CRP) level (P<1×10−4). The same IL1RN 1018 allele was associated with higher mean plasma log(IL-6) levels (P=0.004). In the pooled analysis, the minor allele of IL1RN 13888 (rs2232354) was associated with higher fibrinogen, (P=0.001). The IL1RN 1018 and 13888 variant alleles tag a clade of IL1RN haplotypes linked to allele 1 of an 86-bp VNTR polymorphism. We confirmed that the IL1RN 1018 variant (rs4251961) was associated with decreased cellular IL-1RA production ex vivo. Conclusions—Common functional polymorphisms of the IL1RN gene are associated with several markers of systemic inflammation.

Heart Rate and Subsequent Blood Pressure in Young Adults: The CARDIA Study

The objective of the present study was to examine the hypothesis that baseline heart rate (HR) predicts subsequent blood pressure (BP) independently of baseline BP. In the multicenter longitudinal Coronary Artery Risk Development in Young Adults study of black and white men and women initially aged 18 to 30 years, we studied 4762 participants who were not current users of antihypertensive drugs and had no history of heart problems at the baseline examination (1985-1986). In each race-sex subgroup, we estimated the effect of baseline HR on BP 2, 5, 7, and 10 years later by use of repeated measures regression analysis, adjusting for baseline BP, age, education, body fatness, physical fitness, fasting insulin, parental hypertension, cigarette smoking, alcohol consumption, oral contraceptive use, and change of body mass index from baseline. The association between baseline HR and subsequent systolic BP (SBP) was explained by multivariable adjustment. However, HR was an independent predictor of subsequent diastolic BP (DBP) regardless of initial BP and other confounders in white men, white women, and black men (0.7 mm Hg increase per 10 bpm). We incorporated the part of the association that was already present at baseline by not adjusting for baseline DBP: the mean increase in subsequent DBP was 1.3 mm Hg per 10 bpm in white men, white women, and black men. A high HR may be considered a risk factor for subsequent high DBP in young persons.

Longitudinal associations between body mass index and serum carotenoids: the CARDIA study

Cross-sectional studies report an inverse association between BMI and serum carotenoid concentration. The present study examined the prospective association between BMI and the serum concentration of five carotenoids in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Serum carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, zeaxanthin/lutein, lycopene), BMI, dietary intake, physical activity and dietary supplement use were measured at years 0 and 7 in 3071 black and white male and female participants, who were either persistent smokers or non-smokers. Among non-smokers, year 0 BMI predicted year 7 serum carotenoid levels: obese subjects (BMI > or =30 kg/m2) had an average concentration of the sum of four carotenoids (alpha-carotene +beta-carotene + zeaxanthin/lutein+beta-cryptoxanthin) that was 22 % lower than the concentration among subjects with a BMI of less than 22 kg/m2. In contrast, the sum of carotenoids among smokers was only 6 % lower. Relationships between BMI and serum lycopene were weak. The change from year 0 to year 7 in serum carotenoids, except for lycopene, was inversely associated with the change in BMI among non-smokers but not among smokers. Parallel findings were observed for BMI and serum gamma-glutamyl transferase level. In summary, the observation that BMI predicted the evolution of serum carotenoids during a 7-year follow-up among young non-smoking adults is consistent with the hypothesis that carotenoids are decreased in protecting against oxidative stress generated by adipose tissue, while smokers maintain a minimal level of serum carotenoids independent of adiposity. The results for lycopene were, however, discordant from those of the other carotenoids.

Poland and U.S. collaborative study on cardiovascular epidemiology hypertension in the community: prevalence, awareness, treatment, and control of hypertension in the Pol-MONICA Project and the U.S. Atherosclerosis Risk in Communities Study.

PURPOSE The objectives of this manuscript are to assess differences in blood pressure levels and in hypertension prevalence, awareness, treatment, and control for selected rural and urban areas in the U.S. and Poland, where ischemic heart disease mortality trends are different. METHODS Included are white persons aged 45-64 selected in Minneapolis, MN suburbs [urban] and Washington County, MD [semi-rural] from the U.S. Atherosclerosis Risk in Communities Study (ARIC) surveyed in 1987-89, and in Warsaw [urban] and Tarnobrzeg Province [semi-rural] from Polands Pol-MONICA Project surveyed in 1987-88. Sample sizes were: U.S.--3,696 men, 3,801 women; Poland--875 men, 960 women. RESULTS Mean blood pressures were > 15% higher for Polish samples than for the U.S. (p < 0.01). In multivariable analysis, hypertension was significantly positively related to age and body mass index (BMI) in both U.S. and Polish samples (except age in Polish men), and to heart rate in Polish samples and U.S. rural women. Smoking was significantly negatively related to hypertension in urban Polish and rural U.S. men. Hypertension awareness, treatment, and control were better in U.S. than in Polish samples. In the U.S. > 80% of subjects with hypertension (systolic blood pressure (SBP) > or = 160 mmHg or diastolic blood pressure (DBP) > or = 95 mmHg or on treatment) were controlled whereas in Polish samples < or = 17% of hypertensive men and 16% of hypertensive women were controlled. When SBP > or = 140 mmHg or DBP > or = 90 mmHg or on treatment defined hypertension, control was about 55% in U.S. samples and about 2% in Polish samples. CONCLUSIONS Hypertension prevalence is higher and blood pressure levels are less well controlled in Polish than in U.S. samples. These striking differences can be expected to contribute to opposing trends in coronary heart disease (CHD) mortality in the two countries. Hypertension control programs in the U.S. are almost certainly responsible for much of the observed differences. There is a clear need for similar programs in Poland.

Kidney Stones and Subclinical Atherosclerosis in Young Adults: The CARDIA Study

PURPOSE Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. To our knowledge there has been no previous examination of the relationship between kidney stones and subclinical atherosclerotic disease. We studied the relationship between nephrolithiasis, and carotid wall thickness and carotid stenosis assessed by B-mode ultrasound in the general community using data from the CARDIA study. MATERIALS AND METHODS The CARDIA study is a United States, population based, observational study of 5,115 white and African-American men and women between the ages of 18 and 30 years at recruitment in 1985 to 1986. RESULTS By the year 20 examination 200 (3.9%) CARDIA participants had reported ever having kidney stones. Symptomatic kidney stones were associated with greater carotid wall thickness measured at the year 20 examination, particularly of the internal carotid/bulb region. Using a composite dichotomous end point of carotid stenosis and/or the upper quartile of internal carotid/bulb wall thickness, the association of kidney stones with carotid atherosclerosis was significant (OR 1.6, 95% CI 1.1-2.3, p=0.01), even after adjusting for major atherosclerotic risk factors. CONCLUSIONS The association between a history of kidney stones and subclinical carotid atherosclerosis in young adults adds further support to the notion that nephrolithiasis and atherosclerosis share common systemic risk factors and/or pathophysiology.