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1.
J Am Coll Cardiol ; 75(22): 2836-2850, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32498812

RESUMO

Potassium (K+) is the most abundant cation in humans and is essential for normal cellular function. Alterations in K+ regulation can lead to neuromuscular, gastrointestinal, and cardiac abnormalities. Dyskalemia (i.e., hypokalemia and hyperkalemia) in heart failure is common because of heart failure itself, related comorbidities, and medications. Dyskalemia has important prognostic implications. Hypokalemia is associated with excess morbidity and mortality in heart failure. The lower the K+ levels, the higher the risk, starting at K+ levels below approximately 4.0 mmol/l, with a steep risk increment with K+ levels <3.5 mmol/l. Hyperkalemia (>5.5 mmol/l) has also been associated with increased risk of adverse events; however, this association is prone to reverse-causation bias as stopping renin angiotensin aldosterone system inhibitor therapy in the advent of hyperkalemia likely contributes the observed risk. In this state-of-the-art review, practical and easy-to-implement strategies to deal with both hypokalemia and hyperkalemia are provided as well as guidance for the use of potassium-binders.

3.
Am J Hypertens ; 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32307510

RESUMO

Hypertension is a common condition that is often seen in patients with diabetes. Both diseases increase the risk of morbidity and mortality from CV events and kidney disease progression. Factors that influence blood pressure control in diabetes include the persons' genetic background for hypertension and kidney disease, level of obesity and insulin resistance, the magnitude of pre-existing kidney disease, and lifestyle factors such as level of sodium and potassium intake, sleep quality and exercise effort all of which can affect levels of sympathetic nerve activity and contribute to increased blood pressure variability. Lifestyle intervention is a key component to the effective management of diabetes and hypertension and can markedly reduce event rates of both heart and kidney outcomes. The approach to pharmacologic treatment of blood pressure in diabetes is crucial since certain classes of agents for both blood pressure and diabetes confer significant benefits to reduce cardiorenal outcomes.

4.
Diabetes Obes Metab ; 22 Suppl 1: 69-76, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32267074

RESUMO

Diabetic kidney disease (DKD) is the major cause of kidney failure in the world and the combination of DKD and diabetes mellitus contributes to an additive incidence of worsening cardiovascular mortality rates. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) remain the mainstay of therapy and have reduced kidney function decline in DKD from 8 to 10 to ~4 mL/min/y. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, in the presence of ACE inhibitors or ARB agents, further slowdown DKD progression by an additional 58% to 1.8 mL/min/y. Moreover, SGLT2 inhibitors reduce heart failure risk. However, the normal rate of kidney function decline in humans is between 0.7 and 0.9 mL/min/y, hence, there is still room for improvement. Mineralocorticoid receptor antagonists (MRAs) already have a track record of benefit in heart failure risk reduction, and efficacy in reducing albuminuria and treating resistant hypertension; however hyperkalaemia and other adverse effects preclude their routine use in DKD. Novel non-steroidal MRAs offer a reduced risk of hyperkalaemia, and yet have many benefits that they share with their steroidal cousins. This paper reviews the data for both steroidal and non-steroidal MRAs in DKD and presents some data from soon-to-be-completed ongoing renal and cardiovascular outcome trials in DKD.

7.
Am J Nephrol ; 51(3): 249-254, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31982868

RESUMO

BACKGROUND: Despite the abundance of data documenting the consequences of poor sleep quality on blood pressure (BP), no previous study to our knowledge has addressed the impact of sleep improvement on resistant hypertension among patients with chronic kidney disease (CKD). METHODS: The aim of this pilot study was to determine whether improved sleep quality and duration will improve BP control in patients with resistant hypertension and CKD. It was a prospective single-center cohort study that involved 30 hypertensive subjects with CKD presenting with primary resistant hypertension and poor sleep quality or duration <6 h/night. Sleep quality and duration were modified using either sleep hygiene education alone or adding sleep medication. The cohort's BP was followed every 3 months for 6-month duration. The average home and clinic BPs were collected at each follow-up visit. The primary outcome baseline change in systolic BP (SBP) and diastolic BP (DBP; home and clinic) at 3 and 6 months after documented sleep improvement. Secondary outcomes included change from baseline in mean arterial pressure, and delta SBP after sleep improvement. RESULTS: African American patients represented 50% of the cohort. All patients had evidence of CKD with GFR ≤60 mL/min and were obese with 40% having type 2 diabetes mellitus. The primary endpoint of change in clinic SBP and DBP was significantly reduced at 3 months, baseline 156 ± 15/88 ± 8 vs. 3 months 125 ± 14/73 ± 7 (p < 0.0001). This difference persisted at 6 months. However, there was no further reduction in-home or clinic BPs between the 3- and 6-month periods. Home and clinic average delta SBP change at 3 months from baseline was -34.4 ± 15 and -30.8 ± 19 mm Hg respectively. Delta SBP change was associated with sleep improvement of >6 h/night, that is, gaining an extra 3-4 h' sleep duration, home; R2 = 0.66, p < 0.0001 and clinic; R2 = 0.49, p < 0.0001. CONCLUSION: Optimizing sleep quality and duration to >6 h/night improved BP control and was associated with a significant delta change in SBP within 3 months of follow-up. Physicians should obtain a sleep history in patients with CKD who present with resistant hypertension.

8.
J Am Heart Assoc ; 9(1): e012797, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31902327

RESUMO

Background Improved heart failure (HF) risk stratification after a recent acute coronary syndrome may identify those who can benefit from therapies that reduce HF risk. We aimed to identify clinical and biomarker predictors for expanded HF outcomes in patients with type 2 diabetes mellitus after recent acute coronary syndrome. Methods and Results The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial was a multicenter, non-inferiority, double-masked, placebo-controlled study which randomized 5380 patients with type 2 diabetes mellitus after recent acute coronary syndrome to alogliptin or placebo. Baseline biomarkers were measured in 5154 patients: NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin I, adiponectin, growth-differentiation-factor-15, and galectin-3. Our primary outcome was cardiovascular) death, HF hospitalization, elevated NT-proBNP during follow-up, or loop diuretics initiation. The association between clinical variables, biomarkers, and outcomes were assessed using Cox regression models. In the study population, the median age was 61.0 years, 67.7% were men, and 28.0% had baseline HF (median follow-up was 18 months). In multivariable analyses, NT-proBNP had the strongest association with the primary outcome (per log2, hazard ratio 1.24; Wald χ2 67.4; P<0.0001) followed by a prior HF history (hazard ratio 1.42; Wald χ2 20.8; P<0.0001). A model with clinical variables and biomarkers allowed for risk prediction for expanded HF outcomes (C-statistic=0.72). Discrimination results were similar for cardiovascular death or HF hospitalization. Conclusions Among patients with type 2 diabetes mellitus after recent acute coronary syndrome, the use biomarkers such as N-terminal pro-B-type natriuretic peptide and clinical variables enables risk stratification for expanded HF outcomes. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00968708.

9.
Diabetes Care ; 43(2): 446-452, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757838

RESUMO

OBJECTIVE: To evaluate the impact of once-weekly exenatide (EQW) on microvascular and cardiovascular (CV) outcomes by baseline renal function in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). RESEARCH DESIGN AND METHODS: Least squares mean difference (LSMD) in estimated glomerular filtration rate (eGFR) from baseline between the EQW and placebo groups was calculated for 13,844 participants. Cox regression models were used to estimate effects by group on incident macroalbuminuria, retinopathy, and major adverse CV events (MACE). Interval-censored time-to-event models estimated effects on renal composite 1 (40% eGFR decline, renal replacement, or renal death) and renal composite 2 (composite 1 variables plus macroalbuminuria). RESULTS: EQW did not change eGFR significantly (LSMD 0.21 mL/min/1.73 m2 [95% CI -0.27 to 0.70]). Macroalbuminuria occurred in 2.2% of patients in the EQW group and in 2.5% of those in the placebo group (hazard ratio [HR] 0.87 [95% CI 0.70-1.07]). Neither renal composite was reduced with EQW in unadjusted analyses, but renal composite 2 was reduced after adjustment (HR 0.85 [95% CI 0.74-0.98]). Retinopathy rates did not differ by treatment group or in the HbA1c-lowering or prior retinopathy subgroups. CV outcomes in those with eGFR <60 mL/min/1.73 m2 did not differ by group. Those with eGFR ≥60 mL/min/1.73 m2 had nominal risk reductions for MACE, all-cause mortality, and CV death, but interactions by renal function group were significant for only stroke (HR 0.74 [95% CI 0.58-0.93]; P for interaction = 0.035) and CV death (HR 1.08 [95% CI 0.85-1.38]; P for interaction = 0.031). CONCLUSIONS: EQW had no impact on unadjusted retinopathy or renal outcomes. CV risk was modestly reduced only in those with eGFR ≥60 mL/min/1.73 m2 in analyses unadjusted for multiplicity.

10.
Am J Nephrol ; 50(5): 345-356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31665733

RESUMO

BACKGROUND: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. PATIENTS AND METHODS: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. CONCLUSIONS: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. TRIAL REGISTRATION: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

11.
Am J Nephrol ; 50(5): 333-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31655812

RESUMO

BACKGROUND: Among diabetics, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality, and progression of their underlying disease. Finerenone is a novel, non-steroidal, selective mineralocorticoid-receptor antagonist which has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), while revealing only a low risk of hyperkalemia. However, the effect of finerenone on renal and CV outcomes has not been investigated in long-term trials yet. METHODS: The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease -(FIDELIO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important renal and CV outcomes in T2D patients with CKD. FIDELIO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 5.5 years. FIDELIO-DKD randomized 5,734 patients with an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30-≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death. CONCLUSION: FIDELIO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of renal and CV events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.

12.
Heart Fail Clin ; 15(4): 455-461, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31472881

RESUMO

The kidney is a regulatory organ and accommodates changes in cardiac function. There is cross-talk between the kidney and the heart. In heart failure, the kidney acts as a bystander but also contributes to several maladaptive processes. The pathophysiology of worsening kidney function and its association with prognosis are discussed, as are other aspects of how worsening kidney function contributes to increased cardiovascular risk. Data suggest that morbidity and mortality reduction in people with heart failure and kidney disease requires use of a renin angiotensin system blocker, beta blocker, and mineralocorticoid receptor antagonist, as well as an SGLT 2 inhibitor.


Assuntos
Anti-Hipertensivos , Insuficiência Cardíaca , Nefropatias , Anti-Hipertensivos/classificação , Anti-Hipertensivos/farmacologia , Progressão da Doença , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Rim/efeitos dos fármacos , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Nefropatias/prevenção & controle , Testes de Função Renal
14.
Artigo em Inglês | MEDLINE | ID: mdl-31365087

RESUMO

OBJECTIVE: To develop clinical practice guidelines for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes mellitus (T2DM) in individuals at metabolic risk for developing these conditions. CONCLUSIONS: Health care providers should incorporate regular screening and identification of individuals at metabolic risk (at higher risk for ASCVD and T2DM) with measurement of blood pressure, waist circumference, fasting lipid profile, and blood glucose. Individuals identified at metabolic risk should undergo 10-year global risk assessment for ASCVD or coronary heart disease to determine targets of therapy for reduction of apolipoprotein B-containing lipoproteins. Hypertension should be treated to targets outlined in this guideline. Individuals with prediabetes should be tested at least annually for progression to diabetes and referred to intensive diet and physical activity behavioral counseling programs. For the primary prevention of ASCVD and T2DM, the Writing Committee recommends lifestyle management be the first priority. Behavioral programs should include a heart-healthy dietary pattern and sodium restriction, as well as an active lifestyle with daily walking, limited sedentary time, and a structured program of physical activity, if appropriate. Individuals with excess weight should aim for loss of ≥5% of initial body weight in the first year. Behavior changes should be supported by a comprehensive program led by trained interventionists and reinforced by primary care providers. Pharmacological and medical therapy can be used in addition to lifestyle modification when recommended goals are not achieved.

17.
Eur Heart J Suppl ; 21(Suppl A): A20-A27, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30837801

RESUMO

Hyperkalaemia in patients with chronic disease states can be caused by both abnormalities of potassium homeostasis as well as extrinsic factors such as medication use and potassium intake. In patients with heart failure (HF), chronic kidney disease (CKD), diabetes mellitus (DM), and in those who use renin-angiotensin-aldosterone system inhibitors (RAASi), there is particularly increased risk of chronic or recurrent hyperkalaemia. Hyperkalaemia is often a reason for the suboptimal dosing or complete discontinuation of RAASi. This review presents current options for the management of hyperkalaemia in patients with chronic disease states. It also explores barriers to guideline-mediated RAASi prescribing patterns in these high-risk patients and highlights the unmet need for agents that adequately manage hyperkalaemia in patients with chronic diseases on concomitant RAASi therapy.

18.
Curr Hypertens Rep ; 21(2): 12, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30747296

RESUMO

PURPOSE OF REVIEW: This is an update of data regarding changes in blood pressure using sodium-glucose co-transporter 2 inhibitors (SGLT2i) for the treatment of diabetes. The mechanism of blood pressure lowering by SGLT2i was thought to be due to their osmotic diuretic effects. New data, however, has emerged from meta-analyses and studies of people with impaired kidney function demonstrating similar or greater magnitudes of blood pressure reduction in the absence of significant glycosuria. Potential additional mechanisms are proposed and reviewed. RECENT FINDINGS: Two separate meta-analyses in over 10,000 participants combined demonstrate an average of 4/2 mmHg reduction in blood pressure by SGLT2i. This includes consistency between measurements of in-office and ambulatory blood pressure monitoring. This reduction extends to decreases in nocturnal blood pressure of 2.6 mmHg systolic pressure. These reductions in blood pressure by SGLT2i are also present when added to ongoing treatment with ACE inhibitors or ARBs. In one study, dapagliflozin, when added to a regimen of a renin-angiotensin-aldosterone system (RAAS) antagonist and a diuretic, further lowered in-office systolic pressure by 2.4 mmHg. In contrast, when prescribed to those on a RAAS antagonist plus a calcium channel blocker or RAAS antagonist plus a beta blocker, systolic pressure decreased 5.4 mmHg. Lastly, post hoc analyses of major cardiovascular outcome trials across the spectrum of estimated glomerular filtration rates from 30 to 80 ml/min/1.73 m2 demonstrated similar magnitudes of BP reduction in spite of far less reduction in glucosuria among those with advanced kidney disease. Moreover, recent data implicate the potential for increased ketones associated with SGLT2i contributing to blood pressure lowering in advanced-stage kidney disease. SGLT2i are well established to lower blood pressure. Their mechanism appears to be multifactorial and has a hemodynamic as well as metabolic component contributing to this reduction.


Assuntos
Hipertensão , Inibidores do Transportador 2 de Sódio-Glicose , Simportadores , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Diurese , Glucose , Humanos , Hipertensão/tratamento farmacológico , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
19.
Am J Cardiol ; 123(3): 382-391, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30477800

RESUMO

A deeper understanding of the interplay between the renal axis and cardiovascular (CV) disease is needed in type 2 diabetes mellitus (T2DM). We aimed to explore the prognostic value of a comprehensive panel of renal biomarkers in patients with T2DM at high CV risk. We evaluated the prognostic performance of both serum (Cystatin C) and urine renal biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 protein, and indices of urinary protein excretion) in 5,380 patients with T2DM and recent acute coronary syndromes in the EXAMINE trial. Patients requiring dialysis within 14 days were excluded. Single- and multimarker covariate-adjusted Cox proportional hazards models were developed to predict times to events. Primary endpoint was composite nonfatal myocardial infarction, nonfatal stroke, or CV death. Median age was 61 years, 68% were men, and mean baseline estimated glomerular filtration rate (eGFR) was 74 mL/min/1.73 m2. During median follow-up of 18 months, 621 (11.5%) experienced the primary endpoint and 326 (6.1%) patients had died. All renal biomarkers were robustly associated with adverse CV events in step-wise fashion, independent of baseline eGFR. However, in the multimarker prediction model, only Cystatin C (per 1 SD) was associated with the primary endpoint (hazard ratio [HR] 1.28 [1.14 to 1.45]; p ≤ 0.001), death (HR 1.51 [1.30 to 1.74]; p ≤ 0.001), and heart failure hospitalization (HR 1.20 [0.96 to 1.49]; p = 0.11). Association between Cystatin C and the primary endpoint was similar in baseline eGFR above and below 60 mL/min/1.73 m2 (Pinteraction > 0.05). In conclusion, serum and urine renal biomarkers, when tested alone, independently predict long-term adverse CV events in high-risk patients with T2DM. In an integrative panel of renal biomarkers, only serum Cystatin C remained independently associated with subsequent CV risk. Renal biomarkers informing various aspects of kidney function may further our understanding of the complex interplay between diabetic kidney disease and CV disease.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Biomarcadores/análise , Cistatina C/análise , Feminino , Taxa de Filtração Glomerular , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Lipocalina-2/análise , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco
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