A population-based study of hemoglobin, race, and mortality in elderly persons

Background. Anemia is associated with increased mortality risk. The impact of mildly low hemoglobin concentration (Hb) on risk for mortality remains unclear, especially among blacks. We examined the racial differences between Hb and mortality. Methods. This was a population-based study conducted from 1993 through 2006, in a geographically defined community of Chicago, Illinois. A stratified, random sample of 1806 participants 65 years old or older and 50% black, who were participating in the Chicago Health Aging Project and underwent clinical evaluation. Mortality was ascertained using the National Death Index. Cox proportional hazard models were used to assess the independent relation of Hb to mortality risk. Results. The proportion of participants with anemia by World Health Organization (WHO) criteria (Hb < 13.0 g/dL for men and < 12.0 g/dL for women) was 39% among blacks, and 17% among whites. Blacks had lower mean Hb (12.6 +/- 1.5 g/dL) than did whites (13.5 +/- 1.5 g/dL). In multivariable analysis, anemia was associated with increased mortality risk in blacks (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.43-2.53) and in whites (HR, 1.85; 95% CI, 1.32-2.59). Among blacks, Hb 0-0.9 g/dL below the anemia threshold is associated with increased mortality risk compared to Hb 0-0.9 g/dL above the anemia cutoff (HR, 1.84; 95% CI, 1.21-2.79), Hb 1.1-2.0 g/dL above the anemia cutoff (HR, 1.35; 95% CI, 0.88-2.05) and Hb 2.1-3.0 g/dL above the anemia cutoff (HR, 2.24; 95% CI, 1.12-4.47). The terms for interaction between black ethnicity/race and anemia suggested that blacks did not have a statistically significant difference in mortality risk compared to whites. Subgroup analyses of interaction terms suggested that Hb 0.1-1.0 g/dL above anemia cutoff group, blacks may have lower mortality risk compared to whites in the mildly low normal ranges of Hb (p =.02). Conclusion. Both anemia by WHO criteria and mild reductions in Hb were related to increased risk of mortality in older blacks and whites.     

Renal function and heart failure risk in older black and white individuals: the Health, Aging, and Body Composition Study

BACKGROUND: Chronic kidney disease is a risk factor for heart failure, an association that may be particularly important in blacks who are disproportionately affected by both processes. Our objective was to determine whether the association of chronic kidney disease with incident heart failure differs between blacks and whites. METHODS: The study population comprised participants in the Health, Aging, and Body Composition Study without a diagnosis of heart failure (1124 black and 1676 white community-dwelling older persons). The main predictors were quintiles of cystatin C and creatinine concentrations and estimated glomerular filtration rate. The main outcome measure was incident heart failure. RESULTS: Over a mean 5.7 years, 200 participants developed heart failure. High concentrations of cystatin C and low estimated glomerular filtration rate were each associated with heart failure, but the magnitude was greater for blacks than for whites (cystatin C concentration: adjusted hazard ratio for quintile 5 [> or =1.18 mg/dL] vs quintile 1 [<0.84 mg/dL] was 3.0 [95% confidence interval 1.4-6.5] in blacks and 1.4 [95% confidence interval, 0.8-2.5] in whites; estimated glomerular filtration rate: adjusted hazard ratio for quintile 5 (<59.2 mL/min) vs quintile 1 (>86.7 mL/min) was 2.7 [95% confidence interval, 1.4-4.9] in blacks and 1.8 [95% confidence interval, 0.9-3.6] in whites). For cystatin C, this association was observed at more modest decrements in kidney function among blacks as well. The population attributable risk of heart failure was 47% for blacks with moderate or high concentrations of cystatin C (> or =0.94 mg/dL) (56% prevalence) but only 5% among whites (64% prevalence). CONCLUSION: The association of kidney dysfunction with heart failure appears stronger in blacks than for whites, particularly when cystatin C is used to measure kidney function.     

Serum uric acid and long-term mortality from stroke, coronary heart disease and all causes.

BACKGROUND: Increased serum uric acid (SUA) levels are linked to obesity, dyslipidemia, diabetes and hypertension. Whether SUA carries a risk for coronary heart disease (CHD) and stroke remains uncertain. DESIGN: A prospective cohort study. METHODS: Of an original cohort of middle-aged workers who were examined in 1963 and followed-up for 23 years, 9125 men, free of CHD at entry, are included in this study. Subjects were divided into quintiles according to baseline SUA levels. Hazard ratios (HR) for all-cause, CHD, and stroke mortality were estimated in SUA quintiles, with the third serving as a referent. RESULTS: During follow-up, 2893 deaths were recorded, including 830 ascribed to CHD and 292 to stroke. The HR for all death [1.22, 95% confidence interval (CI) 1.09-1.37] and CHD (1.29, 95% CI 1.05-1.58) were increased in the upper SUA quintile. Fatal stroke showed a U-shaped relationship as both the upper (HR 1.48, 95% CI 1.02-2.17) and bottom (HR 1.43, 95% CI 0.99-2.08) quintiles were associated with a higher risk. Adjustment for confounders reduced the HR of the upper quintile for all outcomes, but did not attenuate the association of the bottom quintile with stroke (HR 1.52, 95% CI 1.04-2.23). When analysed separately by stroke type, the latter association seemed to be stronger for hemorrhagic (HR 3.27, 95% CI 1.14-9.33) than for ischemic stroke (HR 1.34, 95% CI 0.87-2.05). CONCLUSION: In addition to findings supporting increased mortality among hyperuricemic subjects, we identified an association between low SUA levels and fatal stroke, which deserves further investigation.     

Racial differences in the significance of coronary calcium in asymptomatic black and white subjects with coronary risk factors.

OBJECTIVES: To compare the significance of a specific feature of coronary atherosclerosis--coronary calcium--in asymptomatic black and white subjects with coronary risk factors. BACKGROUND: The natural history and clinical evolution of coronary atherosclerosis differs between blacks and whites. Differences in the underlying pathobiology of atherosclerosis may be one determinant of the ethnic variability in the clinical manifestation of coronary atherosclerosis. METHODS: In 1,375 high-risk but asymptomatic subjects (93 blacks [6.8%] and 1,282 whites [93.2%]) with at least one risk factor but no prior evidence of coronary disease, we assessed coronary risk factors, calculated Framingham risk of a coronary event and evaluated coronary calcium with digital subtraction fluoroscopy. We then followed these subjects clinically for 70 +/- 13 months, noting the occurrence of the following coronary events: death due to coronary heart disease (CHD); myocardial infarction (MI); angina pectoris; and performance of coronary bypass or angioplasty. RESULTS: Risk factor profiles were similar in black and white subjects (6-year Framingham risk 15 +/- 7% in blacks, 14 +/- 8% in whites [NS]). Coronary calcium was present in 59.9% of white subjects but only 35.5% of black subjects (p = 0.0001). Nevertheless, after 70 months of follow-up, more blacks than whites (22 blacks [23.7%] vs. 190 whites [14.8%]; p = 0.04) suffered one of the following end points: CHD death, MI, angina or revascularization. The age, gender and coronary risk-adjusted odds ratio of black race for at least one event was 2.16 (95% CI 1.34 to 3.48). CONCLUSIONS: Despite having a lowered prevalence of coronary calcium than high risk whites, high risk blacks suffer more CHD events. Coronary calcium therefore does not carry the same pathobiologic significance in blacks that it does in whites, consistent with the concept that there are specific racial differences in the natural history of CHD and its evolution into clinically manifest events.     

Racial variation in the relationship of anemia with mortality and mobility disability among older adults

Anemia is more common among older blacks than older whites. However, it is unclear whether anemia predicts adverse events similarly in both races. Data on 1018 black and 1583 white adults aged 71 to 82 years were analyzed. Anemia, as defined by World Health Organization (WHO) criteria, was used to predict mortality over 6 years and incidence of mobility disability over 4 years. In proportional hazards models of mortality in whites, the age-adjusted hazard ratio (HR) for anemia in men was 1.96 (95% confidence interval [CI]: 1.35, 2.83) and in women was 2.86 (95% CI: 1.69, 4.82). In contrast, anemia was not associated with mortality in black men (HR = 1.15 [95% CI: 0.77, 1.72]) or women (HR = 1.39 [95% CI: 0.91, 2.14]). Higher mortality rate was observed only in black men with hemoglobin values more than 20 g/L (2.0 g/dL) below the WHO cutoff, whereas mortality rates were elevated in white men with hemoglobin values 1 to 10, 11 to 20, and more than 20 g/L below the WHO cutoff. In conclusion, anemia was significantly associated with increased risk of death and mobility disability in community-dwelling older whites. Conversely, older blacks classified as anemic by WHO criteria were not at risk for adverse events, indicating that alternative criteria are warranted.     

Triglycerides + high-density-lipoprotein-cholesterol dyslipidaemia, a coronary risk factor in elderly women: the CArdiovascular STudy in the ELderly

BACKGROUND: The relationship between serum triglycerides (TG) level and the risk of coronary heart disease (CHD) mortality remains controversial. AIMS: To evaluate whether TG level is a risk factor for CHD in elderly people from general population, and to look for interactions between TG and other risk factors. METHODS: 3257 subjects aged >or= 65 years followed up for 12 years from the CArdiovascular STudy in the ELderly. Blood tests and anthropometric measurements were performed. Continuous items were divided into quintiles and, for each quintile, adjusted hazard ratio (HR) with 95% confidence interval (CI) for CHD mortality was derived by genders from Cox analysis. RESULTS: In women, the HR of being in the fifth rather than in the first quintile of TG was 2.45 (CI 1.48-3.51). In turn, high-density-lipoprotein cholesterol (HDL-C) inversely predicted CHD mortality; the HR of being in the first rather than in the fifth quintiles of HDL-C was 1.52 (CI 1.24-2.36). The risk of CHD mortality further increased up to 3.81 (CI 1.62-5.43) when high TG and low HDL-C were combined. No predictive role for either TG or HDL-C was detected in men. CONCLUSIONS: TG and HDL-C were independent predictors of CHD mortality in elderly women. The combination high TG + low HDL-C quadrupled the risk of CHD mortality in this gender only.     

Heart rate-corrected QT interval prolongation predicts risk of coronary heart disease in black and white middle-aged men and women: the ARIC study

OBJECTIVES: We aimed to study the predictive value of heart rate-corrected QT interval (QTc) for incident coronary heart disease (CHD) and cardiovascular disease (CVD) mortality in the black and white general population, and to validate various QT measurements. BACKGROUND: QTc prolongation is associated with higher risk of mortality in cardiac patients and in the general population. Little is known about the association with incident CHD. No previous studies included black populations. METHODS: We studied the predictive value of QTc prolongation in a prospective population study of 14,548 black and white men and women, age 45 to 64 year. QT was determined by the NOVACODE program in the digital electrocardiogram recorded at baseline. RESULTS: In quintiles of QTc, cardiovascular risk profile deteriorated with longer QTc, and risk of CHD and CVD mortality increased. The high risk in the upper quintile was mostly explained by the 10% with the longest QTc. The age-, gender-, and race-adjusted hazard ratios for CVD mortality and CHD in subjects with the longest 10% relative to the other 90% of the gender-specific QTc distribution were 5.13 (95% confidence interval 3.80 to 6.94) and 2.14 (95% confidence interval 1.71 to 2.69), respectively. The increased risk was partly, but not completely, attributable to other risk factors or the presence of chronic disease. The association was stronger in black than in white subjects. Manual- and machine-coded QT intervals were highly correlated, and the method of rate correction did not affect the observed associations. CONCLUSIONS: Long QTc is associated with increased risk of CHD and CVD mortality in black and white healthy men and women.     

Glycemic index, glycemic load, and cereal fiber intake and risk of type 2 diabetes in US black women

BACKGROUND: Previous studies of carbohydrate quality and risk of type 2 diabetes mellitus have yielded inconsistent findings. Because diet is in part culturally determined, a study of dietary factors in US black women is of interest. METHODS: We used data from the Black Women's Health Study, a prospective cohort study of 59,000 US black women, to examine the association of glycemic load, glycemic index, and cereal fiber with risk of type 2 diabetes. Diet was assessed at baseline in 1995 with a modified version of the National Cancer Institute-Block food frequency questionnaire. RESULTS: During 8 years of follow-up, there were 1,938 incident cases of diabetes. Cox proportional hazards models were used to estimate incidence rate ratios (IRRs) for quintiles of dietary factors, while controlling for lifestyle and dietary factors. Glycemic index was positively associated with the risk of diabetes: the IRR for the highest quintile relative to the lowest was 1.23 (95% confidence interval [CI], 1.05-1.44). Cereal fiber intake was inversely associated with risk of diabetes, with an IRR of 0.82 (95% CI, 0.70-0.96) for the highest vs lowest quintiles of intake. Stronger associations were seen among women with a body mass index (calculated as weight in kilograms divided by height in meters squared) lower than 25: IRRs for the highest vs lowest quintile were 1.91 (95% CI, 1.16-3.16) for glycemic index (P value for interaction, .12) and 0.41 (95% CI, 0.24-0.72) for cereal fiber intake (P value for interaction, .05). CONCLUSION: Increasing cereal fiber in the diet may be an effective means of reducing the risk of type 2 diabetes, a disease that has reached epidemic proportions in black women.     

The influence of sex on cardiovascular outcomes associated with diabetes among older black and white adults

AimsIt is unknown whether sex differences in the association of diabetes with cardiovascular outcomes vary by race. We examined sex differences in the associations of diabetes with incident congestive heart failure (CHF) and coronary heart disease (CHD) between older black and white adults.MethodsWe analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort study of community-dwelling individuals aged ≥ 65 from four US counties. We included 4817 participants (476 black women, 279 black men, 2447 white women and 1625 white men). We estimated event rates and multivariate-adjusted hazard ratios for incident CHF, CHD, and all-cause mortality by Cox regression and competing risk analyses.ResultsOver a median follow-up of 12.5 years, diabetes was more strongly associated with CHF among black women (HR, 2.42 [95% CI, 1.70–3.40]) than black men (1.39 [0.83–2.34]); this finding did not reach statistical significance (P for interaction = 0.08). Female sex conferred a higher risk for a composite outcome of CHF and CHD among black participants (2.44 [1.82–3.26]) vs. (1.44 [0.97–2.12]), P for interaction = 0.03). There were no significant sex differences in the HRs associated with diabetes for CHF among whites, or for CHD or all-cause mortality among blacks or whites. The three-way interaction between sex, race, and diabetes on risk of cardiovascular outcomes was not significant (P = 0.07).ConclusionsOverall, sex did not modify the cardiovascular risk associated with diabetes among older black or white adults. However, our results suggest that a possible sex interaction among older blacks merits further study.     

Racial differences in survival of hepatocellular carcinoma in the United States: a population-based study.

BACKGROUND & AIMS: Survival after hepatocellular carcinoma (HCC) diagnosis is generally dismal, but there are patients with more favorable outcomes. Racial variation in survival of patients with HCC could be associated with observed differences in survival; however this has not been previously examined. METHODS: During 1987-2001, HCC patients were identified from 9 Surveillance, Epidemiology, and End-Results registries. One- and 3-year survival rates were calculated and compared by race. Models were constructed to examine the effects of race on the mortality risk. RESULTS: Asians had the highest 1- and 3-year observed and relative survival, followed by whites, Hispanics, and blacks. Compared with whites, Asians (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.11-1.69) were more likely to receive local or surgical therapy, whereas blacks (OR, 0.62; 95% CI, 0.49-0.78) and Hispanics (OR, 0.81; 95% CI, 0.60-1.09) were less likely to receive therapy. Adjusting for differences in receipt of therapy, stage of HCC, year of diagnosis, and other demographics, Asians (hazard rate [HR], 0.84; 95% CI, 0.78-0.91) maintained a lower mortality risk compared with whites. In adjusted models, Hispanics (HR, 1.13; 95% CI, 1.03-1.24) maintained a higher mortality risk, whereas the mortality risk for blacks became nonsignificant different from whites (HR, 1.06; 95% CI, 0.99-1.14). Last, a 22% improvement in survival was observed between 1987-1991 and 1997-2001, which was mostly explained by increased receipt of local or surgical therapy. CONCLUSIONS: We observed significant racial variation in survival. These variations in survival are partly explained by a lower likelihood of receipt of therapy and more advanced HCC at diagnosis among blacks and Hispanics.     

Prospective study of circulating factor XI and incident venous thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE)

Elevated plasma concentrations of coagulation factor XI may increase risk of venous thromboembolism (VTE), but prospective data are limited. We studied prospectively the associations of plasma factor XI and a key F11 genetic variant with incident VTE in whites and African‐Americans. We measured factor XI in 16,299 participants, initially free of VTE, in two prospective population cohorts. We also measured the F11 single nucleotide polymorphism rs4241824, which a genome‐wide association study had linked to factor XI concentration. During follow‐up, we identified 606 VTEs. The age, race, sex, and study‐adjusted hazard ratio of VTE increased across factor XI quintiles (P < 0.001 for trend), and the hazard ratio was 1.51 (95% CI 1.16, 1.97) for the highest versus lowest quintile overall, and was 1.42 (95% CI 1.03, 1.95) in whites and 1.72 (95% CI 1.08, 2.73) in African‐Americans. In whites, the F11 variant was associated with both factor XI concentration and VTE incidence (1.15‐fold greater incidence of VTE per risk allele). In African‐Americans, these associations were absent. In conclusion, this cohort study documented that an elevated plasma factor XI concentration is a risk factor for VTE over extended follow‐up, not only in whites but also in African‐Americans. In whites, the association of the F11 genetic variant with VTE suggests a causal relation, but we did not observe this genetic relation in African‐Americans. Am. J. Hematol. 90:1047–1051, 2015. © 2015 Wiley Periodicals, Inc.     

Incidence of and Risk Factors for Sick Sinus Syndrome in the General Population

Background

Little is known about the incidence of and risk factors for sick sinus syndrome (SSS), a common indication for pacemaker implantation.

Objectives

This study sought to describe the epidemiology of SSS.

Methods

This analysis included 20,572 participants (mean baseline age 59 years, 43% male) in the ARIC (Atherosclerosis Risk In Communities) study and the CHS (Cardiovascular Health Study), who at baseline were free of prevalent atrial fibrillation and pacemaker therapy, had a heart rate of ≥50 beats/min unless using beta blockers, and were identified as of white or black race. Incident SSS cases were identified by hospital discharge International Classification of Disease-revision 9-Clinical Modification code 427.81 and validated by medical record review.

Results

During an average 17 years of follow-up, 291 incident SSS cases were identified (unadjusted rate 0.8 per 1,000 person-years). Incidence increased with age (hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.47 to 2.05 per 5-year increment), and blacks had a 41% lower risk of SSS than whites (HR: 0.59; 95% CI: 0.37 to 0.98). Incident SSS was associated with greater baseline body mass index, height, N-terminal pro–B-type natriuretic peptide, and cystatin C, with longer QRS interval, with lower heart rate, and with prevalent hypertension, right bundle branch block, and cardiovascular disease. We project that the annual number of new SSS cases in the United States will increase from 78,000 in 2012 to 172,000 in 2060.

Conclusions

Blacks have a lower risk of SSS than whites, and several cardiovascular risk factors were associated with incident SSS. With the aging of the population, the number of Americans with SSS will increase dramatically over the next 50 years.     

Relation of age and race with hospital death after acute myocardial infarction

Background

Prior studies have suggested that young blacks with acute myocardial infarction (AMI) may have higher hospital mortality rates than whites of similar age. However, the influence of age and race on short-term death has not been explored in detail. We examined the relation of age and race on short-term death in a large AMI population and ascertained the factors that may have contributed to differences in mortality rates.

Methods

We compared the crude and adjusted hospital mortality rates stratified by age among 40,903 blacks and 501,995 whites with AMI enrolled in the National Registry of Myocardial Infarction-2 in 1482 participating US hospitals from June 1994 through March 1998.

Results

Overall crude mortality was lower among blacks compared with whites (10.9% vs 12.0%, P < .0001). However, blacks had a significantly higher crude mortality rate compared with the whites in the age groups <65 years (<45 years, and 5-year age groups between 45 and 64 years). There was a statistically significant interaction between age and black race on hospital death (P value for interaction <.001). Each 5-year decrement in age from 85 years was associated with 7.2% higher odds of death in blacks compared with whites (95% CI, 5.7% to 7.6%). After adjusting for differences in the baseline, clinical presentation, early treatment, and hospital characteristics, 5-year decrements in age was still associated with increases in the odds for death in blacks compared with whites (5.4%; 95% CI, 3.6% to 7.2%). This interaction between age and black race was present in both sexes but was stronger among men.

Conclusions

Blacks younger than 65 years had higher hospital mortality rates compared with whites hospitalized for AMI, and decreasing age was associated with progressively higher risk of hospital death for blacks. Differences in the clinical presentation, early treatment, and hospital characteristics could only partly explain this age-race interaction.     

Constipation,laxative use,and colon cancer in a North Carolina population

OBJECTIVE: The aim of this study was to determine whether bowel movement frequency and laxative use and type were associated with risk of colon cancer in white and black men and women. METHODS: We conducted a population-based, case-control study with equal representation by blacks. Eligible subjects between ages 40 and 80 yr residing in urban and rural communities in North Carolina were asked about bowel habits and laxatives during face-to-face interviews. There were 643 cases (349 white, 294 black) and 1048 controls (611 white, 437 black). RESULTS: Constipation, defined as fewer than three reported bowel movements per wk, was associated with a greater than two-fold risk of colon cancer (OR 2.36; 95% CI = 1.41-3.93) adjusted for age, race, sex, and relevant confounders. The association was greater for women (OR 2.69; 95% CI = 1.46-4.94) than for men (OR 1.73; 95% CI = 0.61-4.88) and stronger in blacks than whites. Black women had the highest risk (OR 3.42; 95% CI = 1.60-7.34), which remained significant (OR 3.21; 95% CI = 1.46-7.04) even after excluding subjects with late stage (distant) disease. The OR for constipation was slightly higher for distal than for proximal colon cancers. There was no association with laxative use (OR 0.88; 95% CI = 0.69-1.11). Fiber commercial laxatives appeared to exert a protective effect in a small subgroup. CONCLUSIONS: This study provides support for a positive association between constipation and increased risk for colon cancer. Women, especially black women with constipation, seem to be at the highest risk.     

Reasons for Differences in the Incidence of Venous Thromboembolism in Black Versus White Americans

IntroductionVenous thromboembolism incidence rates are 30%-100% higher in US blacks than whites. We examined the degree to which differences in the frequencies of socioeconomic, lifestyle, medical risk factors, and genetic variants explain the excess venous thromboembolism risk in blacks and whether some risk factors are more strongly associated with venous thromboembolism in blacks compared with whites.MethodsWe measured venous thromboembolism risk factors in black and white participants of the Atherosclerosis Risk in Communities study in 1987-1989 and followed them prospectively through 2015 for venous thromboembolism incidence.ResultsOver a mean of 22 years, we identified 332 venous thromboembolisms in blacks and 578 in whites, yielding 65% higher crude incidence rates per 1000 person-years in blacks. The age and sex-adjusted hazard ratio (95% confidence interval) of venous thromboembolism for blacks compared with whites was 2.04 (1.76, 2.37) for follow-up > 10 years and was attenuated to 1.14 (0.89, 1.46) when adjusted for baseline confounders or mediators of the race association, which tended to be more common in blacks. For example, adjustment for just baseline weight, family income, and concentration of plasma factor VIII reduced the regression coefficient for race by 75%. There were no significant (P < 0.05) 2-way multiplicative interactions of race with any risk factor, except with a 5-single nucleotide polymorphism (5-SNP) genetic risk score (a weaker venous thromboembolism risk factor in blacks) and with hospitalization for heart failure (a stronger venous thromboembolism risk factor in blacks).ConclusionThe higher incidence rate of venous thromboembolism in blacks than whites was mostly explained by blacks having higher frequencies of venous thromboembolism risk factors.     

HbA<Subscript>1c</Subscript> 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.     

Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (The Framingham Heart Study)

A delayed heart rate (HR) recovery after graded exercise testing has been associated with increased all-cause mortality in clinic-based samples. No prior study has examined the association of HR recovery after exercise with the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) events. We evaluated 2,967 Framingham study subjects (1,400 men, mean age 43 years) who were free of CVD and underwent a treadmill exercise test (Bruce protocol) at a routine examination. We examined the relations of HR recovery indexes (decrease in HR from peak exercise) to the incidence of a first CHD or CVD event and all-cause mortality, adjusting for established CVD risk factors. During follow-up (mean 15 years), 214 subjects experienced a CHD event (156 men), 312 developed a CVD event (207 men), and 167 died (105 men). In multivariable models, continuous HR recovery indexes were not associated with the incidence of CHD or CVD events, or with all-cause mortality. However, in models evaluating quintile-based cut points, the top quintile of HR recovery (greatest decline in HR) at 1-minute after exercise was associated with a lower risk of CHD (hazards ratio vs bottom 4 quintiles 0.54, 95% confidence interval [CI], 0.32 to 0.93) and CVD (hazards ratio 0.61, 95% CI 0.41 to 0.93), but not all-cause mortality (hazards ratio 0.99, 95% CI 0.60 to 1.62). In our community-based sample, HR recovery indexes were not associated with all-cause mortality. A very rapid HR recovery immediately after exercise was associated with lower risk of CHD and CVD events. These findings should be confirmed in other settings.     

Risk factors for primary prevention of cardiovascular disease and risk reduction by lipid control: the OMEGA study risk factor sub-analysis

To identify risk factors for cardiovascular disease (CVD) in hypertensive patients with no history of CVD being treated with antihypertensive drugs, we examined subgroup data (n?=?13?052) from the prospective, observational Olmesartan Mega Study to Determine the Relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement (OMEGA) study. Risk factors for CVD, stroke and coronary heart disease (CHD) were examined using a Cox proportional hazards model. In addition, the effect of statin therapy at baseline on CHD prevention was analyzed in dyslipidemic patients. The factors significantly related to CVD were female (hazard ratio [HR]?=?0.637, 95% confidence interval [CI] 0.428–0.948), older age (65–69 years: HR?=?2.165, 95% CI 1.214–3.861; 70–74 years: HR?=?2.324, 95% CI 1.294–4.174; ≥75 years: HR?=?2.448, 95% CI 1.309–4.578), family history of CHD (HR?=?1.993, 95% CI 1.249–3.179), diabetes (HR?=?2.287, 95% CI 1.700–3.078), current smoking (HR?=?2.289, 95% CI 1.512–3.466) and alcohol drinking socially (HR?=?0.589, 95% CI 0.379–0.913). Diabetes was a risk factor for both stroke and CHD, while age, family history of CHD, and sodium intake score were risk factors for stroke alone. Sex, dyslipidemia, smoking and exercise habits were risk factors for CHD alone. The risk of CHD in dyslipidemic patients on statin treatment was comparable to the risk in patients without dyslipidemia (HR?=?1.134, 95% CI 0.604–2.126). However, in dyslipidemic patients not on statin treatment, the HR increased to 1.807 (95% CI 1.156–2.825). In conclusion, some risk factors for CVD in hypertensive patients being treated with antihypertensive drugs with no history of CVD differed between CHD and stroke. These results suggest the importance of managing dyslipidemia with a statin for primary prevention of CHD, as well as the importance of hypertension therapy.     

Electrocardiographic findings and incident coronary heart disease among participants in the Atherosclerosis Risk in Communities (ARIC) study

The associations of many electrocardiographic (ECG) abnormalities at rest with incident coronary heart disease (CHD) are not completely established, and whether individual ECG abnormalities convey similar risk across gender and race is uncertain. We studied the independent association of several ECG findings with incident CHD, testing for effect modification by gender and race, in a large, population-based, prospective cohort study. Findings from the baseline 12-lead electrocardiograms in 1987 to 1989 were classified according to the Minnesota Code in 12,987 black and white men and women, aged 45 to 64 years, who were initially free of CHD and the use of specific cardiac medications. The incidence of CHD was ascertained through 2000. After adjustment for multiple cardiovascular risk factors, the ECG findings that had the highest hazard rate ratios (HRRs) for incident CHD, when considered singly, were left ventricular hypertrophy with ST-T strain pattern in white men (HRR 6.50) and in black women (HRR 2.31) and, in the whole cohort, major (HRR 2.27) and minor (HRR 2.47) ST depression and major T-wave abnormalities (HRR 2.12). Statistically significant associations were also found in the whole cohort for minor Q waves and left ventricular hypertrophy by the Cornell definition, but not for a prolonged QTc interval, major ventricular conduction defects, or ST elevation. In conclusion, several 12-lead ECG findings were independently associated with incident CHD in middle-aged adults. With only a few exceptions, the associations were similar for blacks and whites.     

Orthostatic hypotension and incident chronic kidney disease: the atherosclerosis risk in communities study

Orthostatic hypotension is associated with cardiovascular disease and mortality, but little is known of its association with incident chronic kidney disease. We evaluated this association in the Atherosclerosis Risk in Communities study. Orthostatic hypotension was defined as a decrease in systolic blood pressure ≥ 20 mm Hg or a decrease in diastolic blood pressure ≥ 10 mm Hg within 2 minutes of standing. Incident chronic kidney disease was defined using an estimated glomerular filtration rate < 60 mL/min/1.73 m2, or a coded hospitalization (discharge) or death for chronic kidney disease through 2005, after exclusion of chronic kidney disease at baseline. The associations between orthostatic hypotension and chronic kidney disease were modeled using Cox proportional hazard while adjusting for confounders including resting blood pressure and medications. Among 12 593 participants, 1326 developed chronic kidney disease (6.3 cases per 1000 person-years; median follow-up of 16 years), with higher rates in blacks than whites. An increased risk of chronic kidney disease was observed among persons with orthostatic hypotension compared with those without it (blacks hazard ratio 2.0, 95% CI, 1.5 to 2.8; whites hazard ratio 1.2, 95% CI, 1.0 to 1.6; P for race interaction = 0.02). An alternative chronic kidney disease classification, based on an increase in serum creatinine at the 3- or 9-year follow-up visits, showed significant associations with orthostatic hypotension in both whites and blacks. These findings suggest that orthostatic hypotension increases the risk of chronic kidney disease in middle-aged persons, but race effects vary by choice of chronic kidney disease definition.