Chronic kidney disease (CKD) affects 15–20% of adults globally and causes various complications, one of the most important being cardiovascular disease (CVD). CKD has been associated with many CVD ...subtypes, especially severe ones like heart failure, independent of potential confounders such as diabetes and hypertension. There is no consensus in major clinical guidelines as to how to incorporate the two key measures of CKD (glomerular filtration rate and albuminuria) for CVD risk prediction. This is a critical missed opportunity to appropriately refine predicted risk and personalize prevention therapies according to CKD status, particularly since these measures are often already evaluated in clinical care. In this review, we provide an overview of CKD definition and staging, the subtypes of CVD most associated with CKD, major pathophysiological mechanisms, and the current state of CKD as a predictor of CVD in major clinical guidelines. We will introduce the novel concept of a “CKD Add-on”, which allows the incorporation of CKD measures in existing risk prediction models, and the implications of taking into account CKD in the management of CVD risk.
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•Chronic kidney disease (CKD) increases the risk of various cardiovascular disease (CVD) subtypes.•The incorporation of key CKD measures into CVD risk prediction models is not yet established in major clinical guidelines.•A new “CKD Add-on” method can incorporate these CKD measures into existing CVD risk prediction models.
Background Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice ...and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Study Design Observational study. Setting & Participants 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013). Predictors Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr ) and serum cystatin C level (eGFRcys ) and urine albumin-creatinine ratio. Outcome Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). Results 341 (7%) participants were classified as frail, 1,475 (30%) had eGFRcr < 60 mL/min/1.73 m2 , 2,480 (50%) had eGFRcys < 60 mL/min/1.73 m2 , and 1,006 (20%) had albuminuria with albumin excretion ≥ 30 mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys < 60 mL/min/1.73 m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and albumin-creatinine ratio. Frail individuals with eGFRcr of 60 to <75 mL/min/1.73 m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45-<60, 32% to 30-<45, and 3% to <30 mL/min/1.73 m2 ). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants). Limitations Cross-sectional study design. Conclusions Frail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr . Given the substantial medication burden and uncertainty in chronic kidney disease classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population.
OBJECTIVE: To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with standard diabetes management would reduce glycated hemoglobin ...levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A cluster-randomized clinical trial, the Mobile Diabetes Intervention Study, randomly assigned 26 primary care practices to one of three stepped treatment groups or a control group (usual care). A total of 163 patients were enrolled and included in analysis. The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period. Secondary outcomes were changes in patient-reported diabetes symptoms, diabetes distress, depression, and other clinical (blood pressure) and laboratory (lipid) values. Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support. Patients received automated, real-time educational and behavioral messaging in response to individually analyzed blood glucose values, diabetes medications, and lifestyle behaviors communicated by mobile phone. Providers received quarterly reports summarizing patient’s glycemic control, diabetes medication management, lifestyle behaviors, and evidence-based treatment options. RESULTS: The mean declines in glycated hemoglobin were 1.9% in the maximal treatment group and 0.7% in the usual care group, a difference of 1.2% (P < 0.001) over 12 months. Appreciable differences were not observed between groups for patient-reported diabetes distress, depression, diabetes symptoms, or blood pressure and lipid levels (all P > 0.05). CONCLUSIONS: The combination of behavioral mobile coaching with blood glucose data, lifestyle behaviors, and patient self-management data individually analyzed and presented with evidence-based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year.
Chronic kidney disease (CKD) afflicts many older adults and increases the risk for medication-related adverse events.
The aim of this study was to assess the prevalence and associated morbidity and ...mortality of polypharmacy (use of several medications concurrently), and potentially inappropriate medication (PIM) use in older adults, looking for differences by CKD status.
We quantified medication and PIM use (from Beers criteria, the Screening Tool of Older People's Prescriptions, and Micromedex
) by level of estimated glomerular filtration rate (eGFR) for participants aged 65 years or older attending a baseline study visit in the Atherosclerosis Risk in Communities study (n =6392). We used zero-inflated negative binomial and Cox proportional hazards regressions to assess the relationship between baseline polypharmacy, PIM use, and subsequent hospitalization and death.
Mean age at baseline was 76 (± 5) years, 59% were female, and 29% had CKD (eGFR < 60 ml/min/1.73 m
). Overall, participants reported 6.1 (± 3.5) medications and 2.3 (± 2.2) vitamins/supplements; 16% reported ≥ 10 medications; 31% reported a PIM based on their age. On average, participants with CKD reported more medications. A PIM based on kidney function was used by 36% of those with eGFR < 30 ml/min/1.73 m
. Over a median of 2.6 years, more concurrent medications were associated with higher risk of hospitalization and death, but PIM use was not. While those with CKD had higher absolute risks, there was no difference in the relative risks associated with greater numbers of medications by CKD status.
Polypharmacy and PIM use were common, with greater numbers of medications associated with higher risk of hospitalization and death; relative risks were similar for those with and without CKD.
IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in ...estimated glomerular filtration rate GFR of −57% or greater) is a late event. OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12 344 ESRD events and 223 944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% 95% CI, 6.4%-7.4% of the entire consortium) were more common than changes of −57% (0.79% 95% CI, 0.52%-1.06%). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
Equations for estimating GFR with serum creatinine overestimate measured GFR in Blacks. The authors report new equations, without race as an inflation factor, using cystatin C and creatinine that ...reduced errors in estimation between Black participants and non-Black participants.
Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in ...diverse populations, including patients with higher eGFR.
To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m
and 122,664 participants with eGFR<60 ml/min per 1.73 m
from 14 cohorts followed for an average of 4.2 years.
Slower eGFR decline by 0.75 ml/min per 1.73 m
per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m
(adjusted hazard ratio, 0.70; 95% CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m
(0.71; 95% CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3%, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m
per year over 2 years would reduce the ESKD risk by 1.6%. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58%, the same intervention would reduce the risk by only 0.13%.
Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m
, but those with the highest risk would be expected to benefit the most.
Public statements about the effect of smoking on cardiovascular disease are predominantly based on investigations of coronary heart disease (CHD) and stroke, although smoking is recognized as a ...strong risk factor for peripheral artery disease (PAD). No study has comprehensively compared the long-term association of cigarette smoking and its cessation with the incidence of 3 major atherosclerotic diseases (PAD, CHD, and stroke).
The aim of this study was to quantify the long-term association of cigarette smoking and its cessation with the incidence of the 3 outcomes.
A total of 13,355 participants aged 45 to 64 years in the ARIC (Atherosclerosis Risk In Communities) study without PAD, CHD, or stroke at baseline (1987 to 1989) were included. The associations of smoking parameters (pack-years, duration, intensity, and cessation) with incident PAD were quantified and contrasted with CHD and stroke using Cox models.
Over a median follow-up of 26 years, there were 492 PAD cases, 1,798 CHD cases, and 1,106 stroke cases. A dose-response relationship was identified between pack-years of smoking and 3 outcomes, with the strongest results for PAD. The pattern was consistent when investigating duration and intensity separately. A longer period of smoking cessation was consistently related to lower risk of PAD, CHD, and stroke, but a significantly elevated risk persisted up to 30 years following smoking cessation for PAD and up to 20 years for CHD.
All smoking measures showed significant associations with 3 major atherosclerotic diseases, with the strongest effect size for incident PAD. The risk due to smoking lasted up to 30 years for PAD and 20 years for CHD. Our results further highlight the importance of smoking prevention and early smoking cessation, and indicate the need for public statements to take PAD into account when acknowledging the impact of smoking on overall cardiovascular health.
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Arterial stiffness is suggested as a mediator of cardiorenal interaction. However, previous studies reported inconsistent associations between chronic kidney disease (CKD) and arterial stiffness and ...were limited by using either estimated glomerular filtration rate (eGFR) or albumin-creatinine ratio (ACR) and examining arterial stiffness at limited segments.
Cross-sectional.
3,424 Atherosclerosis in Communities (ARIC) Study participants aged 66 to 90 years during 2011 to 2013.
eGFR and ACR.
Pulse wave velocity (PWV) at 6 segments: carotid-femoral (cfPWV), heart-carotid (hcPWV), and heart-femoral (hfPWV), reflecting central stiffness; heart-ankle (haPWV) and brachial-ankle (baPWV), representing both central and peripheral stiffness; and femoral-ankle (faPWV), indicating peripheral stiffness.
Multiple linear and logistic regression models to quantify the associations of eGFR and ACR with continuous PWV and elevated PWV (in the highest quartile), respectively.
After adjusting for age, sex, and race, higher cfPWV and hfPWV were consistently associated with lower eGFR and higher ACR. Higher haPWV and baPWV were also observed with higher ACR. The independent association of both CKD measures with elevated cfPWV remained consistent after adjusting for additional confounders (ORs of elevated cfPWV were 1.09 95% CI, 1.01-1.18 per 15-mL/min/1.73m2 lower eGFR and 1.20 95% CI, 1.07-1.33 per 4-fold higher ACR). Higher ACR was also associated with elevated hfPWV and haPWV (ORs per 4-fold higher ACR were 1.25 95% CI, 1.12-1.39 for elevated hfPWV and 1.19 95% CI, 1.06-1.33 for elevated haPWV). Lower eGFR was associated with lower odds of elevated baPWV and faPWV (ORs per 15–mL/min/1.73m2 lower eGFR were 0.92 95% CI, 0.84-0.99 and 0.91 95% CI, 0.85-0.99, respectively).
Unable to address temporality between CKD measures and arterial stiffness.
Both lower eGFR and higher ACR are independently associated with measures of central arterial stiffness, with stronger associations for ACR over eGFR. Our findings suggest that central arterial stiffness may be an important pathophysiologic phenotype of vascular disease in CKD.
Arterial stiffness, represented as carotid-femoral pulse wave velocity (cfPWV), predicts cardiovascular disease (CVD). In older populations, however, this association seems attenuated. Moreover, the ...prognostic values of pulse wave velocity at different arterial segments and newer parameters like cardio-ankle vascular index (CAVI) remain unclear, especially in US older adults.In 3034 Atherosclerosis Risk in Communities (ARIC) study participants (66–90 years) without CVD, we examined the associations of 4 pulse wave velocity measures (cfPWV, heart-femoral, brachial-ankle, heart-ankle) and 2 new measures of arterial stiffness (CAVI and cardio-femoral vascular index derived from heart-ankle and heart-femoral, respectively) with incident CVD (coronary disease, stroke, and heart failure) and all-cause mortality.Over a median follow-up of 4.4 years, there were 168 incident CVD events and 244 deaths. Overall, stiffness measures did not show strong associations with CVD, except cfPWV, which demonstrated a J-shaped association even after adjusting for potential confounders (hazard ratio, 1.83 95% CI, 1.08–3.09 in top quartile and 1.97 1.14–3.39 in bottom quartile versus second bottom quartile). When each CVD was examined separately, heart failure was most robustly associated with higher cfPWV, and stroke was strongly associated with lower cfPWV. There were no significant associations with all-cause mortality.Among different measures of pulse wave velocity, cfPWV showed the strongest associations with CVD, especially heart failure, in older adults without CVD. Other pulse wave velocity measures had no strong associations. Our findings further support cfPWV as the index measure of arterial stiffness and the link of arterial stiffness to heart failure development but also suggest somewhat limited prognostic value of arterial stiffness in older adults overall.
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