Cardiovascular risk assessment: addition of CKD and race to the Framingham equation.

BACKGROUND/AIMS: The value of the Framingham equation in predicting cardiovascular risk in African Americans and patients with chronic kidney disease (CKD) is unclear. The purpose of the study was to evaluate whether the addition of CKD and race to the Framingham equation improves risk stratification in hypertensive patients. METHODS: Participants in the ALLHAT were studied. Those randomized to doxazosin, older than 74 years, and those with a history of coronary heart disease were excluded. Two risk stratification models were developed using Cox proportional hazards models in a two-thirds developmental sample. The first model included the traditional Framingham risk factors. The second model included the traditional risk factors plus CKD, defined by estimated glomerular filtration rate categories, and stratification by race (black vs non-black). The primary outcome was a composite of fatal coronary heart disease, nonfatal myocardial infarction, coronary revascularization, and hospitalized angina. RESULTS: There were a total of 19,811 eligible subjects. In the validation cohort, there was no difference in C-statistics between the Framingham equation and the ALLHAT model including CKD and race. This was consistent across subgroups by race and sex and among those with CKD. One exception was among Non-Black women where the C-statistic was higher for the Framingham equation (0.68 vs 0.65, P = .02). In addition, net reclassification improvement was not significant for any subgroup based on race and sex, ranging from -5.5% to 4.4%. CONCLUSION: The addition of CKD status and stratification by race does not improve risk prediction in high-risk hypertensive patients.

Sleep duration and the risk of diabetes mellitus: epidemiologic evidence and pathophysiologic insights.

Evidence from well-defined cohort studies has shown that short sleep, through sleep fragmentation caused by obstructive sleep apnea (OSA) or behavioral sleep curtailment because of lifestyle choices, is associated with increased incidence of diabetes. In this report, we review epidemiologic and clinical data suggesting that OSA is involved in the pathogenesis of altered glucose metabolism. Evidence suggesting increased risk of developing diabetes resulting from curtailed sleep duration is also considered. Proposed mechanisms explaining associations between short sleep and diabetes are examined and clinical management of OSA among patients with diabetes is discussed.

Depression is an important contributor to low medication adherence in hemodialyzed patients and transplant recipients.

End-stage renal disease (ESRD) is a growing public health concern and non-adherence to treatment has been associated with poorer health outcomes in this population. Depression, likely to be the most common psychopathology in such patients, is associated with increased morbidity and mortality. We compared psychological measures and self-reported medication adherence of 94 kidney transplant recipients to those of 65 patients receiving hemodialysis in a major medical center in Brooklyn, New York. Compared to the transplant group, the hemodialysis cohort was significantly more depressed as determined by the Beck Depression Inventory score. They also had a significantly lower adherence to medication as reported on the Medication Therapy Adherence Scale. Using hierarchical multiple regression analysis, the variance in depression was the only statistically significant predictor of medication adherence beyond gender and mode of treatment, accounting for an additional 12% of the variance. Our study strongly suggests that a depressive affect is an important contributor to low medication adherence in patients with ESRD on hemodialysis or kidney transplant recipients.

Cancer worry and insomnia complaints among American women.

One-third of women worrying about breast cancer report impaired ability to function daily. It is unclear whether women who worry about breast cancer would experience more sleep problems than those who do not. Data were obtained from a cross-sectional study of black and white women to investigate the association between breast cancer worry and insomnia complaints. Several questionnaires were administered during face-to-face interviews to elicit health and sociodemographic data. The present analyses focused on black and white women (n = 1,038; age range = 50-70 years) with no cancer antecedents or history. Overall, 62% of the women worried about breast cancer, and 49% reported insomnia complaints. Logistic regression analyses, adjusting for effects of age, ethnicity, family history, and perceived risk of developing breast cancer, yielded an odds ratio for insomnia complaints of 1.52 (95% CI: 1.15-2.02, p < .001) among women reporting breast cancer worry. More than one half of the women worrying about breast cancer were likely to report insomnia complaints, notwithstanding the fact that those women did not have a history of cancer. Although fewer black women reported breast cancer worry and insomnia complaints, they were as affected as white women by the impact of worry on mood and daily activities.

Sleep duration among black and white Americans: results of the National Health Interview Survey.

INTRODUCTION: Epidemiologic studies have shown the importance of habitual sleep duration as an index of health and mortality risks. However, little has been done to ascertain ethnic differences in sleep duration in a national sample. This study compares sleep duration in a sample of black and white participants in the National Health Interview Survey (NHIS). METHOD: Data were collected from 29,818 Americans (age range 18-85 years) who participated in the 2005 NHIS. The NHIS is a cross-sectional household interview survey that uses a multistage area probability design, thus permitting representative sampling of U.S. households. During face-to-face interviews conducted by trained interviewers from the U.S. Census Bureau, respondents provided demographic data and information about physician-diagnosed chronic conditions, estimated habitual sleep duration and functional capacity, and rated their mood. RESULTS: Fisher's exact test results indicated that blacks were less likely than whites to report sleeping 7 hours (23% vs. 30%; chi2 = 94, p < 0.0001). Blacks were more likely to experience both short sleep (< or = 5 hours) (12% vs. 8%, chi2 = 44, p < 0.0001) and long sleep (> or = 9 hours) (11% vs. 9%, chi2 = 23, p < 0.0001). Logistic regression analysis, adjusting for differences in sociodemographic factors, depression, functional capacity and medical illnesses, demonstrated that black ethnicity was a significant predictor of extreme sleep duration (Wald = 46, p < 0.0001; OR = 1.35, 95% CI: 1.24-1.47). DISCUSSION: Independent of several sociodemographic and medical factors, blacks had more prevalent short and long sleep durations, suggesting greater variation in habitual sleep time. Therefore, blacks might be at increased risks of developing medical conditions associated with short and long sleep.

Asymmetric breast enlargement minus central venous thrombosis in a hemodialysis patient.

A 76-year-old woman hemodialysis patient was hospitalized for community-acquired pneumonia complicating chronic obstructive pulmonary disease. End-stage renal disease secondary to hypertension had been diagnosed at the age of 64 for which the patient was initiated on maintenance hemodialysis. Then, she received a deceased donor kidney transplant at the age of 68 that succumbed to chronic rejection 4 years later when she was restarted on hemodialysis. Hemodialysis was performed via a right subclavian vein double lumen catheter for 2 months when a right brachio-axillary graft was inserted. Severe venous congestion, swelling, and nipple tenderness of her right breast noted on admission had been increasing for 6 weeks before hospital admission. No arm swelling was evident. Initial management of the patient's pneumonia and chronic obstructive pulmonary disease consisted of intravenous ceftriaxone and albuterol inhaler to which intravenous oxacillin (1 g q 6 hr) was added for presumed right mastitis. Radiological work-up for masses and malignancies was negative. An angiogram of the right upper extremity detected stenosis of the dialysis access graft at its anastomosis with the axillary vein. Angioplasty of the stenosis was performed without incident or evidence of central vein stenosis. Rapid resolution over 10 days of the unilateral breast congestion followed without complication.

Comparison of efficacy and safety of rosuvastatin versus atorvastatin in African-American patients in a six-week trial.

The lipid-modifying effects of statin therapy in hypercholesterolemic African-Americans have not been well characterized. This study compared the efficacy and safety of rosuvastatin and atorvastatin treatment for 6 weeks in hypercholesterolemic African-American adults. In the African American Rosuvastatin Investigation of Efficacy and Safety (ARIES) trial (4522US/0002), 774 adult African-Americans with low-density lipoprotein cholesterol > or = 160 and < or = 300 mg/dl and triglycerides < 400 mg/dl were randomized to receive open-label rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg for 6 weeks. At week 6, significantly greater reductions in low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B concentrations, as well as lipoprotein and apolipoprotein ratios, were seen with rosuvastatin versus milligram-equivalent atorvastatin doses (analysis of variance with Bonferroni-adjusted critical p < 0.017 for all comparisons). Rosuvastatin 10 mg also increased high-density lipoprotein cholesterol significantly more than atorvastatin 20 mg (p < 0.017). Although statistical comparisons were not performed, larger proportions of rosuvastatin-treated patients than atorvastatin-treated patients achieved National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. The median high-sensitivity C-reactive protein levels were significantly reduced statistically from baseline with rosuvastatin 20 mg and atorvastatin 20 mg among all patients and with rosuvastatin 10 and 20 mg and atorvastatin 20 mg in those patients with a baseline C-reactive protein level > 2.0 mg/L. The 2 study medications were well tolerated during the 6-week study period. In conclusion, rosuvastatin 10 and 20 mg improved the overall lipid profile of hypercholesterolemic African-Americans better than did milligram-equivalent doses of atorvastatin.

The prevalence of reduced glomerular filtration rate in older hypertensive patients and its association with cardiovascular disease: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

BACKGROUND: The prevalence of reduced glomerular filtration rate (GFR) in older hypertensive patients and the relationship between level of GFR and cardiovascular disease (CVD) and its risk factors are not well known. METHODS: We evaluated baseline renal function in 40 514 hypertensive patients 55 years or older who were enrolled in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). We used the simplified Modification of Diet in Renal Disease study equation to estimate GFR and examined the prevalence of CVD in patients with different levels of GFR. RESULTS: Fifty-seven percent of patients had mild (60-89 mL/min per 1.73 m(2)), 17.2% had moderate (30-59 mL/min per 1.73 m(2)), and 0.6% had severe (

Treating azotemia-induced anemia with erythropoietin improves diabetic eye disease.

BACKGROUND: Coincidental with the pandemic growth of diabetes as the prime cause of end-stage renal disease (ESRD), blindness attributable to diabetic retinopathy has become a major concern for all those involved in the care of diabetic ESRD patients. Vision loss is linked to progression of proliferative retinopathy and macular edema. METHODS: Extracted from a study of azotemic anemic pre-ESRD patients treated with erythropoietin, a cohort of five diabetic subjects was reassessed in terms of stability of renal function, changes in blood rheology, and course of diabetic eye disease. RESULTS: All subjects reported subjective improvement in well-being, including enhanced effort tolerance following an increase in hematocrit from a baseline level of to 29.6 +/- 2.0% to a level of 39.5 +/- 2.4% after one year of treatment with erythropoietin (P = <0.0005). Neither hypertension nor deterioration of renal function was noted in any subject. Three patients with macular edema evinced substantive improvement-based stable vision and documented resolution noted in flourescein angiography. CONCLUSION: Erythropoietin treatment of anemic azotemic diabetic patients is well tolerated. In a small observational retrospective study of three patients with macular edema, retention of vision and resolution of exudates was noted.

Telephone-delivered behavioral intervention among blacks with sleep apnea and metabolic syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Lack of adherence to recommended treatment for obstructive sleep apnea remains an ongoing public health challenge. Despite evidence that continuous positive airway pressure (CPAP) is effective and improves overall quality of life, adherence with the use of CPAP in certain racial/ethnic groups, especially blacks, is suboptimal. Evidence indicates that the incidence and prevalence of obstructive sleep apnea are higher among blacks, relative to whites, and blacks are less likely to adhere to recommended treatment compared with other racial/ethnic groups. METHODS: Using a two-arm randomized controlled design, this study will evaluate the effectiveness of a culturally and linguistically tailored telephone-delivered intervention to promote adherence to physician-recommended sleep apnea assessment and treatment among blacks with metabolic syndrome, versus an attention-control arm. The intervention is designed to foster adherence to recommended sleep apnea care using the stages-of-change model. The intervention will be delivered entirely over the telephone. Participants in the intervention arm will receive 10 phone calls to address challenges and barriers to recommended care. Outcomes will be assessed at baseline, and at 6- and 12-months post-randomization. DISCUSSION: This tailored behavioral intervention will improve adherence to sleep apnea assessment and treatment among blacks with metabolic syndrome. We expect to demonstrate that this intervention modality is feasible in terms of time and cost and can be replicated in populations with similar racial/ethnic backgrounds. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov NCT01946659 (February 2013).

Long-term renal and cardiovascular outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants by baseline estimated GFR.

BACKGROUND AND OBJECTIVES: CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged ≥55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4-8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m(2)) as follows: normal/increased (≥90; n=8027), mild reduction (60-89; n=17,778), and moderate/severe reduction (<60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD. RESULTS: After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P<0.001). In participants with an eGFR <60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD. CONCLUSIONS: CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.

Cardiovascular disease risk reduction with sleep apnea treatment.

Cardiovascular diseases are the leading cause of death among adults in developed countries. An increase in prevalent cardiovascular risk factors (e.g., obesity, hypertension and diabetes) has led to a concerted effort to raise awareness of the need to use evidence-based strategies to help patients at risk of developing cardiovascular disease and to reduce their likelihood of suffering a stroke. Sleep apnea has emerged as an important risk factor for the development of cardiovascular disease. Epidemiologic and clinical evidence has prompted the American Heart Association to issue a scientific statement describing the need to recognize sleep apnea as an important target for therapy in reducing cardiovascular disease risks. This article examines evidence supporting associations of sleep apnea with cardiovascular disease and considers evidence suggesting cardiovascular risk reductions through sleep apnea treatment. Perspectives on emerging therapeutic approaches and promising areas of clinical and experimental research are also discussed.

Symptoms of obstructive sleep apnea in a Caribbean sample.

Obstructive sleep apnea (OSA) is a prevalent sleep disorder that disproportionately affects blacks. While clinical and epidemiologic data indicate intraethnic differences in several medical diseases, little is known about whether OSA symptoms differ within the black ethnic group. We estimated the rate of OSA symptoms in a community-based sample of Caribbean-born black men and women. We also ascertained which sociodemographic and/or medical factors were associated with OSA risk. A total of 554 patients (mean age = 48.17 +/- 16.75 years) participated in the study; 55% were women. Data were collected in four primary-care clinics in Brooklyn, NY. A health educator explained the purpose of the study to interested patients and assisted consenting participants in completing questionnaires, which required 15 min to complete. Participants reporting habitual snoring, excessive daytime sleepiness, and sleep fragmentation were considered at high OSA risk. The rate of OSA symptoms was: snoring (45%), excessive daytime sleepiness (33%), and difficulty maintaining sleep (34%). Many reported falling asleep while watching television (47%) or while driving (14%). Based on logistic regression analysis, a history of heart disease was the most important predictor of the likelihood of expressing OSA symptoms, with a corresponding multivariate-adjusted odds ratio of 11 (95% confidence interval = 3.03-40.63). Findings suggest the need to investigate whether Caribbean-born blacks are at greater risk for developing OSA than African Americans and whites. Caribbean-born blacks with a history of heart disease should be a prime target for interventions that promote adequate screening and timely OSA diagnosis.

Obstructive sleep apnea and cardiovascular disease: role of the metabolic syndrome and its components.

Although obstructive sleep apnea and cardiovascular disease have common risk factors, epidemiologic studies show that sleep apnea increases risks for cardiovascular disease independently of individuals' demographic characteristics (i.e., age, sex, and race) or risk markers (i.e., smoking, alcohol, obesity, diabetes, dyslipidemia, atrial fibrillation, and hypertension). Individuals with severe sleep apnea are at increased risk for coronary artery disease, congestive heart failure, and stroke. The underlying mechanisms explaining associations between obstructive sleep apnea and cardiovascular disease are not entirely delineated. Several intermediary mechanisms might be involved including sustained sympathetic activation, intrathoracic pressure changes, and oxidative stress. Other abnormalities such as disorders in coagulation factors, endothelial damage, platelet activation, and increased inflammatory mediators might also play a role in the pathogenesis of cardiovascular disease. Linkage between obstructive sleep apnea and cardiovascular disease is corroborated by evidence that treatment of sleep apnea with continuous positive airway pressure reduces systolic blood pressure, improves left ventricular systolic function, and diminishes platelet activation. Several systematic studies are necessary to explicate complex associations between sleep apnea and cardiovascular disease, which may be compounded by the involvement of diseases comprising the metabolic syndrome (i.e., central obesity, hypertension, diabetes, and dyslipidemia). Large-scale, population-based studies testing causal models linking among sleep apnea, cardiovascular morbidity, and metabolic syndrome are needed.

Evaluation of sleep apnea in a sample of black patients.

OBJECTIVES: Few minority patients with sleep apnea have been evaluated or treated. This study ascertained adherence rate to referrals for sleep apnea evaluation by primary care physicians in a community-based sample of black patients; it also examined baseline characteristics likely to influence adherence rates. METHODS: A retrospective chart audit was conducted at a hospital-based sleep clinic. Scrutiny was limited to male and female patients between the ages of 20 and 80 years. Data obtained for this analysis included baseline characteristics from a detailed sleep history and/or screening questionnaires and polysomnographic parameters. RESULTS: Of the 421 patients referred by their private care physicians, 38% (n=160) adhered to the recommendation for a sleep consultation, but all who showed up for their appointment underwent polysomnographic studies. Logistic regression analyses showed that obesity and daytime sleepiness were the most important factors predicting adherence, with multivariate-adjusted odds ratios of 2.69 [95% CI: 1.54-4.71, p < 0.001] and 6.98 [95% CI: 3.86-12.64, p < 0.001], respectively. Of the patients who underwent a polysomnographic sleep evaluation, 91% received a sleep apnea diagnosis and were treated. CONCLUSIONS: Black patients may be underutilizing available sleep services, but direct comparisons with other ethnic groups could not be made because of insufficient archival data. While the present study does not identify specific barriers to accessing services for sleep problems, it indicates that blacks who are obese and/or are experiencing daytime sleepiness are likely to adhere to recommendations of their physician. Targeted culturally congruent educational interventions to increase awareness of sleep apnea in black communities might help to increase adherence rate.

Cardiovascular risk factors in minorities.

Recent clinical trials have confirmed the value of intervention on major risk factors, particularly hypertension and hyperlipidemia, in preventing the progression and clinical sequelae of atherosclerosis. Less is known about the prevalence and impact of atherosclerosis risk factors in minorities. A review of recent literature reporting the prevalence of established and new predictors of atherosclerotic events in minority populations and the inclusion of minorities in clinical trials is presented. The prevalence of risk factors differs considerably in minority populations. The role of "premature" coronary death and the level of some risk factors, particularly obesity and blood pressure in African descendants and high triglycerides, low high-density lipoproteins, and diabetes in some Hispanics, is higher than in whites. With few exceptions, however, minorities have not been included in clinical trials in sufficient numbers to determine whether significant differences in the benefit of risk factor intervention exists. Prevalence of key risk factors differs among minority groups. Risk factor intervention should be pursued in minority groups but with the understanding that clinical trials have not ruled out the possibility of qualitative or quantitative differences in response rates among different groups.

Association of reduced red blood cell deformability and diabetic nephropathy.

BACKGROUND: Impaired red blood cell deformability may play a key role in the pathogenesis of chronic vascular complications of diabetes mellitus and progression of renal failure. The present study was conducted to test whether impaired red blood cell deformability is indeed associated with development of diabetic nephropathy. METHODS: We studied 57 adult type 2 diabetic patients divided into three groups according to serum creatinine concentration. Group I comprised 28 diabetic patients with normal renal function (serum creatinine concentration <1.5 mg/dL, mean 1.0 +/- 0.3 mg/dL). Group II comprised 10 diabetic patients with renal insufficiency (serum creatinine concentration ranging from 2 to 6 mg/dL, mean 3.9 +/- 1.54 mg/dL). Group III consisted of 19 diabetic subjects with end-stage renal disease (ESRD) on hemodialysis (serum creatinine concentration ranging from 7.7 to 14.6 mg/dL, mean 10.1 +/- 2.4 mg/dL). In addition, 11 (mean serum creatinine concentration 4.2 +/- 1.5 mg/dL) and 10 (mean serum creatinine concentration 11.5 +/- 3.6 mg/dL) nondiabetic individuals, matched renal function for the diabetic groups (group II and III, respectively) served as control. Red blood cell deformability, measured by filtration technique, is defined as the filtration rate of erythrocyte suspension through a micropore filter divided by the filtration rate of a physiologic buffer solution. RESULTS: In the diabetic cohort, we found substantially impaired red blood cell deformability in those with normal renal function (group I). With further renal function loss, an increased impairment in red blood cell deformability was observed. Diabetic patients with renal insufficiency (group II) when compared to non-diabetic controls (renal insufficiency) had a significantly greater impairment in red blood cell deformability (P= 0.01). The nondiabetic cohort (renal insufficiency), on the other hand, manifested significant impairment in red blood cell deformability. Their degree of impairment was statistically higher than that in diabetic patients with normal renal function (P= 0.0005). Interestingly, there was a progressive increase in red blood cell deformability impairment, along with progression of renal insufficiency, and thus no significant difference in the degree of red blood cell deformability impairment was observed between diabetic and nondiabetic patients with ESRD (P= 0.52). There is significant correlation between serum creatinine and impairment in red blood cell deformability in both diabetic (group II plus III) (r= 0.43, P= 0.02) and nondiabetic (r= 0.62, P= 0.003) cohorts. CONCLUSION: In diabetic patients, early impairment in red blood cell deformability appears in patients with normal renal function, and progressive impairment in red blood cell deformability is associated with renal function loss in all patients regardless of the presence or absence of diabetes.

Angiotensinogen gene polymorphism at -217 affects basal promoter activity and is associated with hypertension in African-Americans.

Hypertension is a serious health problem in Western society, in particular for the African-American population. Although previous studies have suggested that the angiotensinogen (AGT) gene locus is involved in human essential hypertension, the molecular mechanisms involved in hypertension in African-Americans remain unknown. We show that an A/G polymorphism at -217 in the promoter of the AGT gene plays a significant role in hypertension in African-Americans. The frequency of the -217A allele was increased significantly in African-American hypertensive subjects compared with normotensive controls. We also show that the nucleotide sequence of this region of the AGT gene promoter bound strongly to CAAT/enhancer-binding protein (C/EBP) family transcription factors when nucleoside A was present at -217. In addition, we show that reporter constructs containing the human AGT gene promoter with nucleoside A at -217 had increased basal transcriptional activity upon transient transfection in HepG2 cells compared with reporter constructs with nucleoside G at -217. Finally, we show that interleukin-6 treatment in the presence or absence of overexpressed C/EBPbeta increased the promoter activities of reporter constructs containing nucleoside A at -217 compared with reporter constructs containing nucleoside G at -217. Because the AGT gene is expressed primarily in liver and adipose tissue, and C/EBP family transcription factors play an important role in gene expression in these tissues, we propose that increased transcriptional activity of the -217A allele of the human AGT gene is associated with hypertension in African-Americans.