Biomedical subjects
Publications and source records attributed to John M Flack.
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BACKGROUND: Early identification of persons at risk for kidney disease provides an opportunity to prevent or delay its progression and decrease morbidity and mortality. Our hypothesis was that implementation of a targeted screening program in communities with high-risk populations would detect previously unidentified persons with or at high risk for chronic kidney disease (CKD) with a prevalence that exceeds that predicted for CKD in the general population. METHODS: Persons with hypertension or diabetes or a first-order relative with hypertension, diabetes, or kidney disease were screened for kidney disease risk factors. Blood pressure, blood glucose level, serum creatinine level, hemoglobin level, microalbuminuria, hematuria, pyuria, body mass index, and estimated glomerular filtration rate (EGFR) were evaluated. RESULTS: Six thousand seventy-one eligible persons were screened from August 2000 through December 2001: of these persons, 68% were women, 43% were African American, 36% were white, 10% were Hispanic, and 5% were Native American. Most reported high-school education or more (84%) and health insurance coverage (86%). Twenty-seven percent met the screening definitions for diabetes; 64%, for hypertension; 29%, for microalbuminuria; 8%, for anemia; 18%, for hematuria; 13%, for pyuria; 5%, for elevated serum creatinine level; 16%, for reduced EGFR; and 44%, for obesity. Among participants without a reported history of specified conditions, screening identified 82 participants (2%) with diabetes, 1,014 participants (35%) with hypertension, 277 participants (5%) with elevated serum creatinine levels, 839 participants (14%) with reduced EGFRs, and 1,712 participants (29%) with microalbuminuria. Thirty-five percent of participants with a history of diabetes had elevated serum glucose levels at screening (> or =180 mg/dL [10 mmol/L]), and 64% with a history of hypertension did not have blood pressure controlled to less than 140/90 mm Hg. Only 18% of participants with a history of diabetes and 31% with a reduced EGFR had blood pressure controlled to less than 130/80 mm Hg and less than 135/85 mm Hg, respectively. CONCLUSION: Targeted screening is effective in identifying persons with previously unidentified or poorly controlled kidney disease risk factors, as well as persons with a moderately decreased EGFR.
Cardiovascular disease (CVD) is the No. 1 cause of mortality in the United States and it disproportionately affects African Americans. However, there are earlier reports that African Americans had significantly less CVD than whites. This racial discrepancy in CVD rates was noticed primarily for coronary heart disease (CHD). This issue was examined in the Evans County (Georgia) Cardiovascular Disease Study conducted in the 1960s. It showed that African American men had significantly lower rates of CHD than white men. Over the last couple of decades, the rates of CVD have been declining. However, the rate of decline of CVD in African Americans has not been equal to that seen in whites, such that African Americans now have a disproportionate share of CVD in the United States. In the 1990s, the Jackson Heart Study was designed to explore the reasons for the current racial discrepancy. This articles reviews the findings of the Evans County Study and explores various hypotheses for why CVD in African Americans has evolved from a disease from which African Americans may have been "protected" to one in which they shoulder a disproportionate burden.
Dyslipidemia is a cardiovascular disease (CVD) risk factor that is associated with enhanced atherosclerosis and plaque instability. Renal insufficiency is associated with abnormalities in lipoprotein metabolism in both the early and the advanced stages of chronic renal failure. These include alterations in apolipoprotein A (apo A)- and B- containing lipoproteins, high-density lipoproteins, and triglycerides. In animal models, these alterations in lipid metabolism and action lead to macrophage activation and infiltration in the kidney with resultant tubulointerstitial and endothelial cell injury. Limited data in humans suggest that, in addition to contributing to CVD, dyslipidemia may be a risk factor for the progression of renal disease. The effects of dyslipidemia on the kidney are mainly observed in those with other risk factors for renal disease progression such as hypertension, diabetes, and proteinuria. Renal disease is a strong risk factor for CVD and African Americans have high rates of renal disease. Therefore, examining the effects of dyslipidemia on the development or progression or renal disease will be an important question for the Jackson Heart Study and is the topic of this review.
Hypertension is a nutritional-hygienic disease. Long-term caloric intake in excess of energy expenditures, chronic supraphysiological intake of dietary sodium, excessive alcohol consumption, and psychosocial stressors all contribute to the development of hypertension throughout the world. Elevated BP, particularly systolic BP, has been linked to multiple adverse clinical outcomes including stroke, heart failure, myocardial infarction, renal insufficiency/failure, peripheral vascular disease, retinopathy, dementia, and premature mortality. These undesirable clinical outcomes are typically, although not invariably, preceded by pressure-related target-organ injury such as left ventricular hypertrophy, renal insufficiency and proteinuria. The relation of BP and CKD and, in turn, the prevention of CKD or forestalling its progression by hypertension treatment, will be the focus of this manuscript. In hypertensive persons with reduced kidney function and/or proteinuria, lowering BP with multidrug therapy that is inclusive of pharmacologic modulators of the renin-angiotensin-aldosterone-kinin system is an effective strategy to forestall the progressive loss of kidney function. The totality of data support low therapeutic BP targets for persons with proteinuria >1 g/d. Nevertheless, in persons with CKD, even those with proteinuria below the dipstick positive level (approximately 300 mg/d or urine protein to creatinine ratio of 0.22), aggressive BP control also may be warranted because of the high risk of nonrenal cardiovascular disease. Multiple antihypertensive drugs will be required in the vast majority of patients with diabetes and/or reduced kidney function to attain BP goal. Renin-angiotensin system (RAS) modulator therapy is indicated among persons with diabetes mellitus and CKD. Available data support the use of angiotensin receptor blockers in persons with type 2 diabetes and overt nephropathy for preservation of kidney function. Among persons with type I diabetes with or without overt nephropathy, type 2 diabetes without overt nephropathy and in nondiabetic CKD, the available clinical data support the use of angiotensin-converting enzyme inhibitors as the RAS modulator of choice. Low therapeutic target BP levels <130/80 mmHg in persons with type 2 diabetes mellitus also appear warranted based on available data mostly for reducing the risk of nonrenal cardiovascular disease and overall mortality.
In 2000, the National Kidney Foundation implemented the Kidney Early Evaluation Program (KEEP 2.0) to increase awareness of kidney disease among those at highest risk, and improve outcomes through early detection and referral for care. The KEEP 2.0 screening program identified significant numbers of persons with reduced kidney function, with previously undetected kidney disease risk factors, and with inadequate risk factor control. These data support the evolution to KEEP 3.0, which will continue to identify individuals at high risk for kidney disease, and will address the educational needs of health care providers and consumers, given that preventing and managing kidney disease requires their joint effort. Consumers need to embrace lifestyle behaviors that reduce risk, and adhere to medical recommendations in managing their existing conditions. At the same time, providers need to ensure that the latest evidence-based guidelines in diagnosis and treatment are being implemented in their clinical practice. KEEP 3.0 participants will be randomly assigned to one of several educational programs that vary on whether they provide individually tailored or nontailored information, with long-term follow-up for evaluation of clinical outcomes. Tailored programs may be more successful in supporting behavioral change as these consider the individuals' "readiness to change." In addition, participant-identified providers will be randomly assigned to one of several educational protocols designed to provide evidence-based recommendations for clinical and pharmaceutical management of kidney disease and risk factors; these programs vary on whether they require active or passive participation of providers. Analytic evaluations will examine changes from baseline in participant kidney disease and risk factor status during follow-up, and estimate the influence of the various educational protocols on both process of care measures and clinical outcomes.
PURPOSE: To provide nurse practitioners (NPs) with updated information regarding the etiology, diagnosis, and treatment of childhood hypertension. DATA SOURCES: Extensive review of the scientific literature regarding hypertension, including the latest NIH recommendations. CONCLUSIONS: Hypertension affects more than 350,000 American children. While the majority of hypertension in early childhood occurs from secondary causes, the incidence of essential hypertension in later childhood and adolescence is rising, raising concerns as elevated pressures in childhood "track" into adulthood. Early detection and treatment of elevated childhood pressures represent important steps in reducing long-term cardiovascular risk. IMPLICATIONS FOR PRACTICE: NPs must be able to accurately differentiate between primary and secondary hypertension in childhood. Secondary hypertension requires prompt diagnosis and treatment, and controlling primary childhood hypertension has lifelong implications. Given the familial predisposition to hypertension, it is important for adult NPs to be aware of the risks faced by children of hypertensive patients.
The Metabolic Syndrome represents a specific clustering of cardiovascular risk factors. One of several recently proposed definitions encompasses 3 or more of the following 5 abnormalities: waist circumference > 102 cm in men or > 88 cm in women, serum triglyceride level > or = 150 mg/dL, high-density lipoprotein cholesterol level < 40 mg/dL in men or < 50 mg/dL in women, blood pressure (BP) > or = 130/> or = 85 mm Hg and serum glucose > or = 110 mg/dL. The diagnosis of Metabolic Syndrome allows early recognition of an increased risk of cardiovascular disease. African Americans have the highest coronary heart disease mortality of any ethnic group in the United States. African-American women and Hispanic men and women have the highest prevalence of the Metabolic Syndrome. This phenomenon is attributable mainly to the disproportionate occurrence of elevated BP, obesity, and diabetes in African Americans, and the high prevalence of obesity and diabetes in Hispanics. Management of the Metabolic Syndrome consists primarily of modification or reversal of the root causes and direct therapy of the risk factors. The first strategy involves weight reduction and increased physical activity, both of which can improve all components of the syndrome. The second strategy often involves drug treatment of the individual risk factors to further improve BP, lipids, and glucose thereby decreasing the risk of cardiovascular disease. This comprehensive review is provided as part of the educational activities of the African-American Lipid and Cardiovascular Council (AALCC).
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This article discusses various aspects of hypertension in selected special populations. The groups discussed herein are children, pregnant women, African Americans, persons with kidney insufficiency, kidney transplant survivors, and persons with diabetes mellitus. These groups present unique epidemiological, diagnostic and therapeutic challenges for the practitioner. The detection of reduced kidney function merits special attention since it attenuates the blood pressure response to antihypertensive therapy, affects therapeutic decision-making, is both a cause and consequence of poorly controlled hypertension, often lurks undetected, and is excessively prevalent in some special populations.
The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial is a large clinical trial of omapatrilat, a vasopeptidase inhibitor, in patients with stage 1 isolated systolic hypertension (ISH). OPERA is the first study to examine whether effective antihypertensive treatment can provide survival and clinical end point benefits in older persons with this common condition. This 5-year multinational, randomized, double-blind, parallel-group, placebo-controlled, forced-titration study will be conducted in approximately 12,600 subjects randomized by approximately 1100 study centers worldwide over a recruitment period of approximately 2 years. The primary objective of OPERA is to determine whether treatment with once-daily omapatrilat (target dose 40 mg) will reduce cardiovascular (CV) morbidity and mortality in older (> or = 65 years) men and women with enhanced risk for atherosclerotic events due to stage 1 ISH plus other risk factors for which currently there is no evidence-based requirement for treatment. Blood pressure inclusion criteria are systolic blood pressure (SBP) 140 to 159 mm Hg (SBP 125 to 139 mm Hg in diabetic individuals) and diastolic blood pressure (DBP) <90 mm Hg. The primary end point is defined as the composite of fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, fatal/nonfatal heart failure, and other CV mortality. Secondary end points include the individual components of the primary end point, CV mortality, and major cardiovascular end points, as well as effects on cognitive function and initiation of treatment for diabetes. Additional analyses will be conducted in men and women, in diabetic patients, in different risk classes and according to prior evidence of vascular disease.
Cardiovascular disease (CVD) is the No. 1 cause of death in patients with end-stage renal disease (ESRD) and is approximately 3 to 5 times that of non-uremic control subjects. Moreover, higher rates of CVD are seen in patients with moderate and even mild renal dysfunction, particularly if the patient has hypertension or diabetes. Recent studies have indicated that even modest elevations in serum creatinine and urinary albumin excretion are associated with increased CVD risk, not only in persons with diabetes or hypertension but also in the general population. In addition, recent studies have suggested that targeting the kidney and/or kidney specific endpoints (via the renin-angiotensin-aldosterone-kinin system) in the treatment of hypertension, diabetes, and heart failure slows progression of renal disease and reduces the risk of extra-renal micro- and macrovascular complications. We conclude that it is important to screen for renal disease in those with hypertension, diabetes, and other CVD risk factors because it predicts those who are at high risk for major CVD events.
DESIGN: We report the results of a 24-week, placebo-controlled, two-period, crossover trial of sodium supplementation in 112 normotensive African Americans, aged 25 to 64 years, with average blood pressure (BP) of 105/70 mm Hg. Estimated 24-hour urinary sodium excretion was 133.6 mmol; the average urinary sodium-to-creatinine ratio was 0.74. METHODS: Variability-adjusted BP change was the difference in BP level after the respective treatment periods, divided by the intra-person standard deviation of the average BP obtained at 3 consecutive screening visits during a 4-week period. RESULTS: The urinary sodium-to-creatinine ratio and the total urine sodium content were 37.8% and 26.5% higher, respectively, at the end of the sodium treatment period. Twenty-four hour ambulatory BP change (mm Hg) (95% CI) was systolic 1.2 (0, 2.4), and diastolic 0.7 (-0.3, 1.8); cuff BP change was systolic 0.9 (-1, 2.9), and diastolic 1.4 (0.1, 2.7). Variability-adjusted BP change was systolic 0.2 (-0.4, 0.8) and diastolic 0.4 (-0.1, 0.9). Though variability-adjusted and unadjusted SBP change correlated highly (r = 0.941, P<.001), only the former correlated with body mass index (r = 0.224, P<.05), a known correlate of salt sensitivity. While total urinary sodium content in timed urine collections and urinary sodium-to-creatinine ratio correlated (r = 0.727, P<.001), neither correlated with cuff BP changes. Change in urinary sodium-to-creatinine ratios of 3 consecutive pooled overnight 8-hour urine collections correlated with changes in 24-hour ambulatory SBP (r = 0.294, P<.001) and DBP (r = 0.193, P<.05); however, change in total urinary sodium content was uncorrelated. Total urinary sodium content of these pooled collections (P = .001), but not the urinary sodium-to-creatinine ratio, was positively related to urinary creatinine excretion per kilogram of body weight, the latter being an indicator of urine collection duration. CONCLUSIONS: The lack of effect of the duration of urine collection on the urinary sodium-to-creatinine ratio is advantageous in individuals who may report inaccurately the duration of their urine collection. Sequential regression analyses demonstrated that the urinary sodium-to-creatinine ratio conveyed all of the changes in urinary sodium excretion information contained in aggregate urinary sodium excretion-and more. Variability-adjusted BP change was the more sensitive metric of BP response to dietary sodium manipulations, than unadjusted BP change. Thus, variability-adjusted BP change and the urinary sodium-to-creatinine ratio appear to be incrementally better metrics of salt sensitivity than those traditionally used.
The burden of kidney disease is disproportionately high in African Americans, and the condition often remains undiagnosed until late-stage disease. In order to reduce this burden, strategies must be implemented to improve the detection of kidney disease, and preventative measures must be targeted at those at greatest risk of disease. Important risk factors among African Americans in the US include hypertension, diabetes, and obesity. In this review, we discuss screening strategies that will allow earlier detection of kidney disease. The sensitivity of serum creatinine, proteinuria, and microalbuminuria as markers of disease are discussed, as is the importance of calculating glomerular filtration rates in individual patients. Implementation of community-based programs, such as the Kidney Early Evaluation Program developed by the National Kidney Foundation, can offer screening for kidney disease and its risk factors, and can educate and protect African Americans at risk of this prevalent disease.
This research evaluated the effect of inadequate blood pressure (BP) control on selected cardiovascular (CV) disease outcomes and costs for American patients with hypertension. The results of a hypertension outcomes trial, which provided incidence rates for CV disease morbidity and mortality at distinct systolic/diastolic BP ranges, were integrated with U.S. hypertension statistics from the Third National Health and Nutrition Examination Survey and cost estimates for stroke, congestive heart failure, and myocardial infarction. A model was developed to estimate the number of cases and costs of myocardial infarction, stroke, and congestive heart failure for patients achieving BP control versus those not achieving control. For the U.S. population with hypertension, inadequate BP control was estimated to result in 39,702 CV events, 8,374 CV disease deaths, and $964 million in direct medical expenditures. Within the medicated population with CV disease, the incremental costs of failure to attain BP goals reached approximately $467 million. These results reflect the importance of adequate BP control--in particular, systolic BP control--in reducing cardiovascular morbidity, mortality, and overall health care expenditures among patients with hypertension.