Chronic Kidney Disease as a Predictor of Cardiovascular Disease (from the Framingham Heart Study)

doi:10.1016/j.amjcard.2008.02.095

The American Journal of Cardiology

Volume 102, Issue 1, 1 July 2008, Pages 47-53

https://doi.org/10.1016/j.amjcard.2008.02.095 Get rights and content

Chronic kidney disease (CKD) is a risk factor for cardiovascular disease (CVD), although shared risk factors may mediate much of the association. CKD and CVD were related in the setting of specific CVD risk factors, and whether more advanced CKD was a CVD risk equivalent was determined. The Framingham Heart Study original cohort (n = 2,471, mean age 68 years, 58.9% women) was studied. Glomerular filtration rate was estimated (eGFR) using the simplified Modification of Diet in Renal Disease Study equation. CKD was defined as eGFR <59 (women) and <64 ml/min/1.73 m² (men), and stage 3b CKD was defined as eGFR of 30 to 44 (women) and 30 to 50 ml/min/1.73 m² (men). Cox proportional hazard models adjusting for CVD risk factors were used to relate CKD to CVD. Effect modification by CVD risk factors was tested for. Overall, 23.2% of the study sample had CKD (n = 574, mean eGFR 50 ml/min/1.73 m²) and 5.3% had stage 3b CKD (n = 131, mean eGFR 42 ml/min/1.73 m²). In multivariable models (mean follow-up 16 years), stage 3 CKD was marginally associated with CVD (hazard ratio [HR] 1.17, 95% confidence interval [CI] 0.99 to 1.38, p = 0.06), whereas stage 3b CKD was associated with CVD (HR 1.41, 95% CI 1.05 to 1.91, p = 0.02). Testing CVD risk equivalency, the risk of CVD for stage 3b CKD in subjects with previous CVD was significantly lower compared with subjects with previous CVD and no stage 3b CKD (age- and sex-adjusted HR for CVD 0.66, 95% CI 0.47 to 0.91, p = 0.01). Low high-density lipoprotein cholesterol modified the association between CKD and CVD (p = 0.004 for interaction). Stage 3b CKD was associated with CVD, but was not a CVD risk equivalent. In conclusion, CVD risk in the setting of CKD is higher in the setting of low high-density lipoprotein cholesterol.

Section snippets

Methods

The Framingham Heart Study is a community-based prospective cohort study of CVD and its risk factors that began in 1948, consisting of 5,209 men and women in the original cohort.¹ Subjects were invited to attend examinations every 2 years. The study sample for the present investigation consisted of original-cohort subjects attending examination cycle 15 (1977 to 1979). Of 2,632 participants attending the 15th examination cycle, 67 had missing covariate data and 94 had missing creatinine values,

Results

Mean age of our study sample was 68 years, and 58.9% were women. Mean overall follow-up was 16 years. In study subjects, 574 (23.2%) had CKD. Of these, 131 (22.8%) had stage 3b CKD. Those with CKD were older, tended to have lower mean HDL cholesterol, and had a higher prevalence of hypertension and diabetes (Table 1). Relative to those with stage 3a CKD, subjects with stage 3b CKD were older, more likely to be hypertensive and have diabetes, and had high rates of prevalent CVD. eGFR in those

Discussion

In a community-based cohort of men and women, stage 3 CKD was associated with a 20% increased risk of CVD and CHD after adjustment for age and sex, whereas stage 3b CKD was associated with a 50% increased risk of CVD, which remained significant in multivariable-adjusted models. CKD and stage 3b CKD were associated with all-cause mortality in age- and sex-adjusted models, but not after accounting for CVD risk factors and prevalent CVD. Stage 3b CKD did not constitute a CVD risk equivalent. The

Acknowledgments

Dr Fox had full access to all data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. The funding sources had no role in the study design, analyses, or drafting of the manuscript. The National Heart, Lung, and Blood Institute reviews all manuscripts submitted for publication, but was not involved in the decision to publish.

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Cited by (94)

Anticoagulation in Patients With Advanced Chronic Kidney Disease: Walking the Fine Line Between Benefit and Harm
2019, Canadian Journal of Cardiology
Chronic kidney disease affects more than 3 million Canadians and is highly associated with cardiovascular diseases that require anticoagulation, such as atrial fibrillation and venous thromboembolism. Patients with chronic kidney disease are at a problematic crossroads; they are at high risk of thrombotic conditions requiring anticoagulation and bleeding complications due to anticoagulation. The limited high-quality clinical evidence to guide decision-making in this area further compounds the dilemma. In this review, we discuss the physiology and epidemiology of bleeding and thrombosis in patients with kidney disease. We specifically focus on patients with advanced kidney disease (estimated glomerular filtration rate ≤ 30 mL/min) or who are receiving dialysis and focus on the nephrologist perspective regarding these issues. We summarize the existing evidence for anticoagulation use in the prevention of stroke with atrial fibrillation and provide practical clinical recommendations for considering anticoagulation use in this population. Last, we examine specific scenarios such as the use of a glomerular filtration rate estimating equation and dosing, the use of existing prediction tools for stroke and hemorrhage risk, current patterns of anticoagulation use (including during the dialysis procedure), and vascular calcification with vitamin K antagonist use in patients with chronic kidney disease.
L’insuffisance rénale chronique touche plus de trois millions de Canadiens et est fortement associée à des maladies cardiovasculaires nécessitant une anticoagulothérapie, dont la fibrillation auriculaire et la thromboembolie veineuse. Or, les patients atteints d’insuffisance rénale chronique se trouvent dans une situation doublement problématique : ils présentent à la fois un risque élevé d’affections thrombotiques nécessitant une anticoagulothérapie mais aussi de complications hémorragiques résultant de cette anticoagulothérapie. Le peu de données cliniques probantes de haute qualité susceptibles d’orienter la prise de décisions dans ce contexte complique le dilemme. Dans le présent article, nous abordons la physiologie et l’épidémiologie de l’hémorragie et de la thrombose chez les patients atteints de néphropathie. Nous mettons tout particulièrement l’accent sur le cas des patients atteints d’insuffisance rénale avancée (débit de filtration glomérulaire estimé ≤ 30 ml/min/1,73 m²) ou sous dialyse et envisageons la question du point de vue du néphrologue. Nous résumons les données probantes actuelles plaidant en faveur de l’anticoagulothérapie dans la prévention des accidents vasculaires cérébraux (AVC) en cas de fibrillation auriculaire et formulons des recommandations de pratique clinique touchant le recours aux anticoagulants au sein de cette population. Enfin, nous examinons des scénarios précis, comme l’utilisation d’une équation permettant d’estimer le débit de filtration glomérulaire et la détermination de la dose à administrer, l’utilisation des outils existants servant à prévoir le risque d’AVC et d’hémorragie, les modalités actuelles de l’anticoagulothérapie (notamment en cours de dialyse) et la calcification vasculaire associée à l’administration d’antivitamine K chez les patients atteints d’insuffisance rénale chronique.
A novel quantitative approach to the measurement of abdominal aortic calcification as applied to the Canadian Multicenter Osteoporosis Study (CaMOS)
2017, Bone
Lateral spine radiographs provide an inexpensive resource for characterizing abdominal aortic calcification (AAC). A widely accepted measurement of AAC is the semi-quantitative technique generated by the Framingham Heart Study (F-AAC-24). We sought to develop an analytical method to quantify ACC (Q_AAC) on lateral spine radiographs and compare the finding to conventional subjective measurements.
Severity of AAC was quantified by measuring pixel intensities in the user-defined region of the aorta with internal standardization to the vertebral endplates and background calibration to the density of the vertebral body. The association between bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) and AAC measured by Q_AAC, F-AAC-24 and a modified Framingham score (F-AAC-12) was determined in 110 participants of the Canadian Multicenter Osteoporosis Study (CaMOS).
The inter-observer reliability for the Q_AAC was slightly higher than with the visual and semi-quantitative Framingham method and the pseudo-colored images illustrate the potential to meaningfully resolve severity of calcification. There was a significant negative association between Q_AAC and BMD measures of the hip and spine. This association remained significant after adjustment for age, sex, estimated glomerular filtration rate, phosphate and hypertension. Significant predictors of F-ACC-12 and 24 included age and hypertension.
The Q_AAC is a reproducible approach to measuring AAC. Whether it is capable of monitoring subtle calcific changes over time requires further study. This technique could be applied to large studies that seek to determine the impact of interventions that modify bone density as a treatment for vascular calcification and cardiovascular disease in the general population.
Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017
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Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout.
The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function.
Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function.
Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI.
Bill & Melinda Gates Foundation.
Pure Membranous Lupus Nephritis: Description of a Cohort of 150 Patients and Review of the Literature
2019, Reumatologia Clinica
The course and long-term outcome of pure membranous lupus nephritis (MLN) are little understood. The aims of this study are to evaluate the clinical features, course, outcome and prognostic indicators in pure MLN and to determine the impact of ethnicity and the type of health insurance on the course and prognosis of pure MLN.
We conducted a retrospective review of medical records of 150 patients with pure MLN from Spain and the USA.
Mean age was 34.2 ± 12.5 and 80% were women. Sixty-eight percent of patients had nephrotic syndrome at diagnosis. The average serum creatinine was 0.98 ± 0.78 mg/dl. Six percent of patients died and 5.3% developed end-stage renal disease (ESRD). ESRD was predicted by male sex, hypertension, dyslipidemia, high basal 24 h-proteinuria, high basal serum creatinine and a low basal creatinine clearance. Age, cardiac insufficiency, peripheral artheriopathy, hemodialysis and not having received mycophenolate mofetil or antimalarials for MLN predicted death.
Pure MLN frequently presents with nephrotic syndrome, high proteinuria and normal serum creatinine. Its prognosis is favourable in maintaining renal function although proteinuria usually persists over time. Baseline cardiovascular disease and not having a health insurance are related with poor prognosis.
Los conocimientos sobre el curso y el desenlace a largo plazo de la nefritis lúpica membranosa (NLM) pura son todavía escasos. El objetivo de este estudio es evaluar las características clínicas, curso, desenlace e indicadores pronósticos de la NLM y determinar el impacto de la etnicidad y tipo de cobertura sanitaria en el curso y pronóstico de la NLM.
Se realizó una revisión retrospectiva de las historias de 150 pacientes con NLM de España y Estados Unidos.
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Scores underestimate the prediction of cardiovascular risk (CVR) as they are not validated in patients with chronic kidney disease (CKD). Two of the most commonly used scores are the Framingham Risk Score (FRS-CVD) and the ASCVD (AHA/ACC 2013). The aim of this study is to evaluate the predictive ability of experiencing a cardiovascular event (CVE) via these 2 scores in the CKD population.
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View all citing articles on Scopus

: The Framingham Heart Study was supported by the National Heart, Lung, and Blood Institute, Bethesda, Maryland (N01-HC-25195).

: Dr Parikh is currently at Beth Israel Deaconess Medical Center.

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Preventive cardiologyChronic Kidney Disease as a Predictor of Cardiovascular Disease (from the Framingham Heart Study)

Section snippets

Methods

Results

Discussion

Acknowledgments

An approach to longitudinal studies in a community: the Framingham Study

Ann N Y Acad Sci

K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification

Am J Kidney Dis

A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equationModification of Diet in Renal Disease Study Group

Ann Intern Med

Predictors of new-onset kidney disease in a community-based population

JAMA

Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate

Am J Kidney Dis

Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Study, 30-year follow-up

Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency

Kidney Int

Moderate renal insufficiency and the risk of cardiovascular mortality: results from the NHANES I

Kidney Int

Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke

Stroke

Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community

J Am Coll Cardiol

Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies

J Am Soc Nephrol

Ethnic disparities in cardiovascular risk factors and coronary disease prevalence among individuals with chronic kidney disease: findings from the Third National Health and Nutrition Examination Survey

J Am Soc Nephrol

Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization

N Engl J Med

Preventive cardiology
Chronic Kidney Disease as a Predictor of Cardiovascular Disease (from the Framingham Heart Study)