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Biomedical subjects

George Bakris

Publications and source records attributed to George Bakris.

At least 19 recordsLinked to original sources
PubMed2023

Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria.

BACKGROUND: Sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone all individually reduce cardiovascular, kidney, and mortality outcomes in patients with type 2 diabetes and albuminuria. However, the lifetime benefits of combination therapy with these medicines are not known. METHODS: We used data from 2 SGLT2i trials (CANVAS [Canagliflozin Cardiovascular Assessment] and CREDENCE [Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation]), 2 ns-MRA trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease]), and 8 GLP-1 RA trials to estimate the relative effects of combination therapy versus conventional care (renin-angiotensin system blockade and traditional risk factor control) on cardiovascular, kidney, and mortality outcomes. Using actuarial methods, we then estimated absolute risk reductions with combination SGLT2i, GLP-1 RA, and ns-MRA in patients with type 2 diabetes and at least moderately increased albuminuria (urinary albumin:creatinine ratio ≥30 mg/g) by applying estimated combination treatment effects to participants receiving conventional care in CANVAS and CREDENCE. RESULTS: Compared with conventional care, the combination of SGLT2i, GLP-1 RA, and ns-MRA was associated with a hazard ratio of 0.65 (95% CI, 0.55-0.76) for major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). The corresponding estimated absolute risk reduction over 3 years was 4.4% (95% CI, 3.0-5.7), with a number needed to treat of 23 (95% CI, 18-33). For a 50-year-old patient commencing combination therapy, estimated major adverse cardiovascular event-free survival was 21.1 years compared with 17.9 years for conventional care (3.2 years gained [95% CI, 2.1-4.3]). There were also projected gains in survival free from hospitalized heart failure (3.2 years [95% CI, 2.4-4.0]), chronic kidney disease progression (5.5 years [95% CI, 4.0-6.7]), cardiovascular death (2.2 years [95% CI, 1.2-3.0]), and all-cause death (2.4 years [95% CI, 1.4-3.4]). Attenuated but clinically relevant gains in event-free survival were observed in analyses assuming 50% additive effects of combination therapy, including for major adverse cardiovascular events (2.4 years [95% CI, 1.1-3.5]), chronic kidney disease progression (4.5 years [95% CI, 2.8-5.9]), and all-cause death (1.8 years [95% CI, 0.7-2.8]). CONCLUSIONS: In patients with type 2 diabetes and at least moderately increased albuminuria, combination treatment of SGLT2i, GLP-1 RA, and ns-MRA has the potential to afford relevant gains in cardiovascular and kidney event-free and overall survival.

Humans↗
PubMed2006

Is it time for a cardiovascular primary prevention trial in the elderly?

BACKGROUND AND PURPOSE: Statins have been shown conclusively to reduce the risk of cardiovascular events in subjects with clinical cardiovascular disease or diabetes aged 65 to 80 years of age. However, few data are available for primary prevention of cardiovascular disease in those aged > or =70 years. SUMMARY OF REVIEW: A moderate-dose statin was of little benefit in a population aged 70 to 82 years when given for 3 years in the setting of suboptimally treated blood pressure. More evidence supports the use of blood pressure-lowering medications, but few data are available regarding the appropriate blood pressure target and most effective agents in the elderly. Some evidence also suggests that the elderly could experience higher mortality with antihypertensive treatment. These findings, along with greater safety concerns and an increasing number of competing risks and medical conditions with advancing age, make it imperative to carefully evaluate the risk/benefit balance from treating hypercholesterolemia and hypertension in persons aged > or =70 years. CONCLUSIONS: We propose a 5-year 2x2 factorial trial of primary prevention in the elderly that will (1) evaluate whether statin therapy will reduce the risk of cardiovascular events when added to the treatment of hypertension to achieve a blood pressure <140/90 mm Hg in most patients and (2) determine the most appropriate blood pressure regimen for the prevention of cardiovascular and renal events.

Aged↗
PubMed2006

The role of hyperglycaemia and the hypercoagulable state in the pathogenesis of cardiovascular events in diabetes mellitus: implications for hypertension management.

Population studies have identified diabetes mellitus as a risk factor for cardiac and vascular events, with a common association with hypertension. Observational studies have consistently demonstrated blood glucose as a continuous cardiovascular risk factor. Experimental studies suggest that elevated blood glucose, through a range of biochemical pathways can promote atherogenesis and increase the tendency for thrombosis. The resultant state promotes occlusion of arterial flow and increase cardiovascular event rates. However, an unconvincing temporal relationship (raised blood glucose preceding cardiovascular events) and the limited impact of glucose reduction in patients with diabetes on cardiovascular events do not support blood glucose as a major cause of cardiovascular disease. In this review, we discuss the relationship between hyperglycaemia and a hypercoagulable state in diabetes and the implications of this relationship for the treatment of patients with diabetes, who also commonly have hypertension.

Blood Coagulation↗
PubMed2006

Differences in glucose tolerance between fixed-dose antihypertensive drug combinations in people with metabolic syndrome.

OBJECTIVE: We sought to test the hypothesis that a fixed-dose combination of trandolapril/verapamil-SR (T/V) is superior to a fixed-dose combination of losartan/hydrochlorothiazide (L/H) on glucose tolerance in hypertensive patients with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A prospective, randomized, open-label, blinded-end points design was used to assess the effects of a T/V versus L/H combination in patients with IGT and hypertension (n = 240) followed for up to 1 year. Doses were titrated to a systolic blood pressure <130 mmHg. Primary outcome was change from baseline in a 2-h glucose on oral glucose tolerance test (OGTT) at study end (mean [+/-SD] at follow-up, 46.9 +/- 13.5 weeks). Secondary outcomes included changes in insulin sensitivity, office and 24-h ambulatory blood pressure, incidence of new-onset diabetes, lipids, and inflammatory markers. Data are expressed as means +/- SE unless otherwise noted. RESULTS: Changes at study end were noted in 2-h OGTT glucose (T/V -0.21 +/- 0.36 vs. L/H +1.44 +/- 0.36 mmol/l; P < 0.001) and insulin level (-30.13 +/- 38.38 vs. +84.86 +/- 38.33 pmol/l, respectively; P = 0.025). Worsening of insulin resistance occurred by week 12 (T/V 0.000 +/- 0.001 vs. L/H -0.005 +/- 0.001; P = 0.016). A higher incidence of new-onset diabetes (T/V 11.0 vs. L/H 26.6%; P = 0.002) and HbA1c >7% (2.6 vs. 9.6%, respectively; P = 0.05) occurred at study end. CONCLUSIONS: In patients with IGT, normal kidney function, and hypertension, the fixed-dose combination of T/V reduces the risk of new-onset diabetes compared with an L/H-based therapy.

Adult↗
PubMed2005

Effects of drospirenone/17-beta estradiol on blood pressure and potassium balance in hypertensive postmenopausal women.

BACKGROUND: Drospirenone (DRSP) is a novel progestin with aldosterone receptor antagonist activity developed for hormone therapy as DRSP /17-beta estradiol (DRSP/E2). Because of a significant aldosterone antagonist activity, we studied the effects of DRSP/E2 on serum potassium (K) and blood pressure (BP) in hypertensive postmenopausal women with and without diabetes mellitus. METHODS: This was a multicenter trial in postmenopausal women 44 to 70 years of age, either with type 2 diabetes mellitus (n = 82) or without type 2 diabetes mellitus (n = 148) and using an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor antagonist. Patients were randomized to 28 days of DRSP/E2 or placebo. Study endpoints were the number and percentage subjects who developed hyperkalemia (K >or= 5.5 mEq/L) and changes from baseline in clinic systolic and diastolic BP. To increase the likelihood of unmasking hyperkalemia, the nondiabetic group was also administered ibuprofen for 5 days. RESULTS: There were no statistical differences in the overall number and percentage of subjects with hyperkalemia for DRSP/E2 versus placebo. No subject had symptoms or electrocardiographic changes related to hyperkalemia. Blood pressure was reduced by -8.6/-5.8 mm Hg in patients receiving DRSP/E2 versus -3.7/-2.9 mm Hg in those receiving placebo (P < .01 for both SBP and DBP). CONCLUSIONS: In hypertensive postmenopausal women, treatment with DRSP/E2 was not associated with a greater incidence of hyperkalemia than with placebo in patients with and without type 2 diabetes mellitus and concomitant use of ACE inhibitors, angiotensin receptor antagonists, or ibuprofen. Furthermore, DRSP/E2 was found to have a significant antihypertensive effect in this high-risk population.

Administration, Oral↗
PubMed2005

Control of blood pressure and other cardiovascular risk factors at different practice settings: outcomes of care provided to diabetic women compared to men.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes. To determine the proportion of patients who met the American Diabetes Association guidelines for control of CVD risk factors and to assess the achievement of these guidelines in women compared with men, we conducted a cross-sectional study of 3678 diabetic cohorts followed at seven medical centers, two Veteran Administration hospitals, three urban clinics, and two suburban clinics. Overall, 28% met the target blood pressure of <130/80 mm Hg, 48.8% achieved a goal low-density lipoprotein cholesterol of <100 mg/dL, and 35.8% had hemoglobin A1c of <7%. Gender comparisons of 2788 diabetic patients at urban and suburban centers showed that women had a lower percentage of low-density lipoprotein cholesterol <100 mg/dL (45.8 vs. 51.3, p<0.01) and a lower percentage of screening for retinopathy (54 vs. 60, p<0.01) and nephropathy (37 vs. 49, p<0.01). However, overall there were no gender differences in the percentage of patients who achieved a goal blood pressure <130/80 mm Hg or hemoglobin A1c <7%. Control of blood pressure and other CVD risk factors in diabetic patients was largely suboptimal, especially for diabetic women. These observations underscore the need for better strategies for control of CVD risk in the diabetic population in general, and women in particular.

Aged↗
PubMed2004

ImmunoDip: an improved screening method for microalbuminuria.

BACKGROUND: It is important to test for microalbuminuria in patients with diabetes, hypertension and possible insulin resistance syndrome. Current screening methods are suboptimal. This study evaluates a new office screening test for microalbuminuria that utilizes a monoclonal antibody against human serum albumin (ImmunoDip). METHODS: 182 urine samples were collected from patients attending diabetes, nephrology or hypertension clinics. The ImmunoDip screening test was carried out in the 182 samples after which albumin and creatinine concentrations were measured quantitatively in a reference laboratory. RESULTS: Screening the 182 patient samples with ImmunoDip and designating an albumin:creatinine ratio of > or =30 microg/mg as positive yielded a sensitivity of 96%, a specificity of 80%, a positive predictive value (PPV) of 66% and a negative predictive value (NPV) of 98%. The reduced specificity and PPV were not due to an intrinsic inaccuracy with ImmunoDip screening of these samples, but rather was shown to be due to the discordance between the accepted upper limits of normal for the albumin:creatinine ratio (30 microg/mg) and the albumin concentration (20 mg/l), the latter corresponding to a ratio of 20 microg/mg. In 35 samples with albumin concentrations of 20-50 mg/l, ImmunoDip screening yielded only one false negative (FN) result. CONCLUSIONS: ImmunoDip is an excellent screening tool for microalbuminuria.

Albuminuria↗
PubMed2004

Inclusion of albuminuria in hypertension and heart guidelines.

The current recommendations by all United States guideline committees, including the American Diabetes Association and the JNC 7, include screening for microalbuminuria in those with diabetes or evidence of kidney disease, but not the general population. Internationally, both the Canadian and European Guidelines have concurred with this approach. This recommendation is due in part to the findings from long-term outcome studies that measurement of microalbuminuria, while a strong predictor of cardiovascular risk, fails to shows change in CV events if reduced. Unfortunately, this conclusion may be wrong because no randomized trial has examined the question of whether a reduction in microalbuminuria does correlate with a reduction in CV events. Thus, we don't know the answer to this question. Additionally, a recent cost-effective analysis was just published, suggesting it is not worth measuring urinary albumin because it is too expensive for the information obtained. Unfortunately, these conclusions were based on the same faulty logic that relates changes in microalbuminuria to cardiovascular events. It is clear that microalbuminuria is a cardiovascular risk factor, acknowledged by both the JNC 7 and the European Guidelines. Moreover, presence of microalbuminuria correlates strongly with elevated levels of C-reactive protein and abnormal vascular responsiveness to vasodilating stimuli. Thus, its presence indicates abnormal responses by vascular tissue, perhaps due to underlying inflammatory responses. Every clinical trial that has assessed changes in albuminuria as a secondary end point with clinical outcomes has shown a strongly positive correlation between reduction in albuminuria and greater protection of a given end organ; this effect is, in part, independent of blood pressure reduction. Thus, what is needed is a clinical trial in people at high cardiovascular risk, such as those in the INVEST or ALLHAT trials where the primary end point is change in albuminuria and its relationship to cardiovascular outcomes. Likewise, a cardiovascular primary end point could relate to the secondary end point of changes in microalbuminuria, and the latter powered appropriately to make stronger statements about albuminuria and cardiovascular outcomes. With this data, guidelines can then make much strong statements about intervention on this marker of risk.

Albuminuria↗
PubMed2003

Blood pressure, antihypertensive therapy and risk for renal injury in African-Americans.

PURPOSE OF REVIEW: African-Americans are more likely than Caucasians to develop hypertension-related end-stage renal disease. Elevations in blood pressure levels clearly potentiate pre-existing renal disease and also contribute to kidney injury independently of other primary renal diseases in this cohort. Until recently, data relevant to a full examination of the issue of blood pressure levels and end-stage renal disease in African-Americans have largely been from post-hoc analyses of clinical trials or from small, prospective, short-term studies. RECENT FINDINGS: The most recent United States Renal Data Systems data show hypertension as the primary cause of end-stage renal disease in African-Americans until 1997, diabetes now being the most prevalent etiology. Data from post-hoc analyses of the Modification of Diet in Renal Disease study demonstrated that African-Americans with a mean arterial pressure above 98 mmHg had a higher risk of end-stage renal disease than Caucasians. The African-American Study of Kidney Disease tested the hypothesis that a blood pressure well below the usual recommended level will further reduce renal disease progression in African-Americans. The study concluded that a blood pressure lower than that needed to reduce cardiovascular events, as defined by the Sixth Joint National Committee Report on the Detection, Evaluation and Treatment of High Blood Pressure, i.e. 135-140/80-85 mmHg, will not further slow renal disease progression in African-Americans with hypertensive nephrosclerosis. Moreover, a regimen of blood pressure lowering anchored on angiotensin-converting enzyme inhibitors, antihypertensive agents that are touted as ineffective in African-Americans, was more effective than one based on either beta-blockers or dihydropyridine calcium-channel blockers in slowing the progression of renal injury. SUMMARY: Systolic blood pressure reduction in the range 130-139 mmHg is appropriate to reduce risk of nephropathy progression and cardiovascular risk in African-Americans with hypertensive nephrosclerosis. Moreover, a regimen that is initiated with an angiotensin-converting enzyme inhibitor should be the antihypertensive treatment of choice in African-Americans with kidney disease.

Antihypertensive Agents↗
PubMed2003

Design and statistical aspects of the African American Study of Kidney Disease and Hypertension (AASK).

The African American Study of Kidney Disease and Hypertension (AASK) is a multicenter randomized clinical trial designed to test the effectiveness of three anti-hypertensive drug regimens and two levels of BP control on the progression of hypertensive kidney disease. Participants include African-American men and women aged 18 to 70 yr who have hypertensive kidney disease and GFR between 20 and 65 ml/min per 1.73 m(2). The three anti-hypertensive drug regimens include an angiotensin converting enzyme inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine) or a beta-blocker (metoprolol) as initial therapy. The BP control levels are a lower goal (mean arterial pressure, </=92 mmHg) and a usual goal (mean arterial pressure, 102 to 107 mmHg inclusive). The primary outcome is rate of change in renal function as measured by GFR, assessed by (125) I-iothalamate clearance. The main secondary patient outcome is a composite including the following events: (1) reduction in GFR by 50%, (2) end-stage renal disease, or (3) death.

Adolescent↗
PubMed2003

The rationale and design of the AASK cohort study.

Hypertensive kidney disease commonly progresses. The primary objective of the AASK (African American Study of Kidney Disease and Hypertension) Cohort Study is to determine prospectively the course of kidney function and risk factors for kidney disease progression in African Americans with hypertensive kidney disease who receive recommended anti-hypertensive therapy. The AASK Cohort Study is a prospective, observational study that is an extension of the AASK trial. The AASK trial tested the effects of three medications used as initial anti-hypertensive therapy (ramipril, metoprolol, and amlodipine) and two levels of BP control. Of the 1094 trial participants, approximately 650 to 700 individuals who have not reached ESRD will likely enroll in the Cohort Study. Risk factors to be studied include environmental, genetic, physiologic, and socioeconomic variables. The primary renal outcome is a composite clinical outcome defined by doubling of serum creatinine, ESRD, or death. Medication treatment for hypertension, beginning with the angiotensin converting enzyme inhibitor ramipril, is offered to all participants. In this fashion, the study directly controls two of the major determinants of kidney disease progression: treatment of hypertension and use of renoprotective, anti-hypertensive medication. The minimum duration of follow-up in the Cohort Study is 5 yr (total of 9 to 12 yr, including the period of the AASK trial). Ultimately, data from the AASK Cohort Study should enhance our understanding of the risk factors and processes that determine the progression of kidney disease. Such results might eventually lead to new strategies that delay or prevent ESRD.

Adolescent↗