CARDIOVASCULAR DISEASE IN

CKD
 Spectrum of Cardiovascular Pathology
in Patients with Chronic Kidney Disease
 Arterial Disease
arteriosclerosis (“hardening of the arteries”)
• ARTERIOSCLEROSIS : encompasses three different lesions:
atherosclerosis, arteriolosclerosis, and Mönckeberg’s medial calcific
sclerosis

• Atherosclerosis, “atheroma” (gruel-like material): lipid-enriched

plaques in the intimal layer of the artery. Calcification is an
important feature of atherosclerosis.

• Arteriolosclerosis: phenomenon of noncalcified, nonatheromatous

stiffening of smaller muscular arteries

• Mönckeberg’s sclerosis: involving the media of the artery and

characterized by medial thickening and heavy calcification without
the presence of atheroma
 Arterial Wall Thickening
• Greater medial thickening in sections of coronary
artery in CKD vs non-CKD patients age- and
gender-matched non-CKD patients known to have
had coronary artery disease

• Ultrasonography (carotid intima-media

thickening, or CIMT)

• CIMT has also been shown to be a strong

predictor of death from cardiovascular causes in
patients with CKD
 Arterial Stiffening
• functional consequence of artery wall
thickening (and calcification) and is readily
assessed noninvasively by measuring the
velocity of propagation of a pulse wave
through the arterial tree

• prognostic significance : both carotid and

aortic stiffness independently predict death in
adult patients receiving hemodialysis
• Stiffness parameter : determined by
monitoring pulsatile changes in the artery
during echo-tracking sonography
 Arterial Calcification
• calcification is a recognized feature of atherosclerosis
and Mönckeberg’s sclerosis

• atherosclerosis : patchy intimal calcification in

association with lipid deposits

• Mönckeberg’s disease : linear pattern of medial

calcium deposition

• calcification can be detected by both ultrasonographic

and radiographic techniques
 CARDIAC DISEASE
• 74% having increased left ventricular mass in one
study

• Left ventricular remodelling may be detectable

even in patients with stage 2 or 3 CKD

• reduced compliance of the left ventricular wall

during diastole (diastolic dysfunction) and
impaired myocardial contractility (systolic
dysfunction), or both
Changes to Left Ventricular Geometry
patients starting dialysis, found that

• 44% predominantly left ventricular wall

thickening (concentric hypertrophy)

• 30% had increased cavity volume (eccentric

hypertrophy)
Ultrastructural Changes to the
Myocardium
• myocardial fibrosis (pale
staining) disrupting the
normal architecture of
cardiac myocytes.
 Changes to Left Ventricular Function
• Echocardiographic studies suggest that systolic
dysfunction is present in approximately 20% of
dialysis patients

• Diastolic dysfunction is more common than

systolic dysfunction in dialysis patients, being
present in approximately 50% of patients
undergoing dialysis

• associated with an even worse prognosis than

systolic dysfunction
 Valvular Diseases
• Calcification of the mitral and/or aortic valve
is four times more common in patients
receiving dialysis

• symptomatic aortic stenosis with resulting

pressure overload of the left ventricle)

• incompetence of the mitral valve (which

further contributes to volume overload)
 Conduction Defects

• impaired intracardiac conduction, manifest as

prolongation of the PQ and QRS intervals

• twofold to threefold increases in the risk of

arrhythmias
 Clinical Manifestations of Cardiovascular
Disease
in Chronic Kidney Disease

• SCD in the CKD population is 2.8%, five times

that in the general population

• meta-analysis of 19 studies has shown that for

each 20 mL/min/1.73 m2 reduction in eGFR,
the risk of a major vascular event (which
includes both nonfatal and fatal events)
increases by about 50%
 Association between Albuminuria
and Cardiovascular
Disease
• microalbuminuria (<30 mg/mmol) was associated
with a 50% increase in risk of coronary artery
disease (HR = 1.47; 95% CI = 1.30 to 1.66)

• macroalbuminuria (30 mg/mmol) was

independently associated with a doubling of risk
(HR = 2.17; 95% CI = 1.87 to 2.52)

• The association between albuminuria and

cardiovascular risk appears to be independent of
GFR
RISK FACTORS
• Direct risk factors (e.g., hypertension) that
arise as a direct consequence of kidney
damage and are associated with one or more
types of cardiovascular disease

• Indirect risk factors (e.g., diabetes mellitus,

cigarette smoking, obesity) that cause both
kidney disease and one or more types of
cardiovascular disease.
 Direct Risk Factors
• Hypertension: mediated by salt and water
retention , sympathetic overactivity, activation of
the renin-angiotensin system, and accumulation
of endogenous vasopressors.
• In turn, hypertension can damage the kidneys
further, which leads to a vicious cycle of rising
blood pressure and declining GFR
• 10 mL/min reduction in GFR leads directly (i.e.,
causally) to a 5 mm Hg increase in systolic blood
pressure
• every 5 mm Hg reduction associated with a
reduction of about one fifth in risk.
 Dyslipidemia
• accumulation of VLDL, IDL, which leads to
elevated TG, with low HDL levels

• LDL cholesterol concentration in CKD is similar to

or lower than the population average

• nephrotic-range proteinuria leads to an increase

in LDL cholesterol

• lipoprotein (a) [Lp(a)] concentrations are

increased in association with CKD
 Anemia
• In CKD anemia is related to left ventricular
hypertrophy

• in one study a 0.5 g/dL lower hemoglobin

concentration was associated with a 30%
higher frequency of increased left ventricular
mass
 Elevated Homocysteine Level
• Homocysteine concentrations have a strong
inverse association with GFR

• the mechanisms underlying

hyperhomocysteinemia in CKD are complex
and not fully understood

• involve metabolic disturbances in

remethylation and transsulfuration pathways
 Coagulation Defects
• increase fibrinogen concentrations

• increases factor VIII and von Willebrand factor

concentrations
 Chronic Kidney Disease–Associated
Mineral Bone Disorder
• Higher serum phosphate concentrations are associated
with increased vascular stiffness and calcification

• Hyperphosphatemia can induce vascular smooth

muscle cells to develop an osteoblastic phenotype

• Framingham Offspring Study, a 1 mg/dL (0.32 mmol/L)

increment in serum phosphate concentration was
associated with an increase in the risk of cardiovascular
disease
 Vitamin D
• unclear whether disturbed vitamin D
metabolism could plausibly contribute to the
observed excess risk of cardiovascular disease
in CKD
 Parathyroid Hormone
• PTH has been implicated in atherogenesis
(and in calcification of atherosclerotic lesions)

• There does not appear to be a clear

association between PTH and all-cause and
cardiovascular mortality in patients with CKD
 Oxidative Stress
• reduction in nitric oxide bioavailability

• endothelial dysfunction

• trials of antioxidant agents does not reduce

the risk of cardiovascular disease
 Elevated Asymmetric Dimethyl
Arginine Level

• inhibits nitric oxide synthetase

• limits the bioavailability of nitric oxide, which

is essential for normal endothelial function
 Indirect Risk Factors
• Diabetes Mellitus
• Obesity
• Cigarette Smoking
MANAGEMENT
 Cardiovascular Risk Prevention
National Kidney Foundation, recommend a target blood
pressure
of less than 140/90 vs 130/80 mm Hg in CKD patients

• Perindopril Protection Against Recurrent Stroke Study

(PROGRESS):active therapy was associated with a 30%
reduction in the risk of major cardiovascular event

• Heart Outcomes and Prevention Evaluation (HOPE)

study:the proportional reduction in cardiovascular
death, myocardial infarction, and stroke resulting from
allocation to treatment with ramipril 10 mg daily was
similar in patients with impaired kidney function and in
those without
• Reduction of Endpoints in NIDDM with the
Angiotensin II Antagonist Losartan (RENAAL)
study failed to demonstrate that losartan reduced
cardiovascular morbidity and mortality

• meta-analysis, treatment producing a reduction

of 4 to 5 mm Hg in mean systolic and 2 to 3 mm
Hg in diastolic blood pressure was associated
with a 29% reduction in both cardiovascular
events and cardiovascular mortality compared
with control regimens
Reduction of Low-Density Lipoprotein
Cholesterol
• Except in the presence of nephrotic-range
proteinuria, blood LDL cholesterol concentration
is not normally raised in patients with CKD

• not the main contributor to an increased risk of

atherosclerosis in patients with CKD

• reducing blood LDL cholesterol may be an

effective strategy for reducing such risk, and a
number of randomized trials have addressed this
hypothesis
 Kdigo guidelines
• In adults aged >50 years with CKD and Egfr >60
ml/min/1.73 m2 (GFR categories G1-G2) recommend
treatment with a statin. (1B)

• CKD but not treated with chronic dialysis or kidney

transplantation, we suggest statin treatment in people
with one or more of the following (2A):
1. known coronary disease (myocardial infarction or
coronary revascularization)
2. diabetes mellitus
3. prior ischemic stroke
4. estimated 10-year incidence of coronary death or
non-fatal myocardial infarction >10%
• In adults with dialysis-dependent CKD, statins
or statin/ezetimibe combination not be
initiated. (2A)

• In patients already receiving statins or

statin/ezetimibe combination at the time of
dialysis initiation, these agents be continued.
(2C)

• in adult kidney transplant recipients,

treatment with a statin. (2B)
 Tight Glycemic Control
• meta-analysis of the available randomized
trials supported the hypothesis that stricter
glycemic control (with HbA1C lower, on
average, by 0.9%) reduces the risk of
cardiovascular events (odds ratio = 0.85; 95%
CI = 0.77 to 0.93
 Correction of Anemia
• results of these key trials do not support the
concept that correction of anemia using
erythropoiesis-stimulating agents reduces
cardiovascular risk in CKD patients

• Trial to Reduce Cardiovascular Events with

Aranesp Therapy (TREAT)

• Correction of Hemoglobin and Outcomes in Renal

Insufficiency (CHOIR)
 Phosphate
• have been no placebo-controlled trials
investigating the benefits of lowering
phosphate level
 Reduction of Homocysteine Level
• Homocysteinemia in Kidney and End Stage Renal
Disease (HOST) study

• there was no difference in mortality (448 deaths

in the treated group vs. 436 in the placebo group;
HR = 1.04; 95% CI = 0.91 to 1.18), nor was there a
reduction in cardiovascular events, including
myocardial infarction, stroke, or amputation of
the lower extremity
 Vitamin D
• no trials of treatment with vitamin D have
been designed specifically to investigate
clinical outcomes such as fractures,
cardiovascular events, or mortality among
patients with CKD
 Antiplatelet Therapy
• antiplatelet therapy yielded a 41%
proportional reduction in the risk of nonfatal
myocardial infarction, nonfatal stroke, or
vascular death, which was consistent with the
proportional benefit observed among other
high-risk patients studied, but there were
insufficient data on bleeding risk to assess
safety
KHA CARI guidelines
 REVASCULARIZATION
• patients with chronic kidney disease (CKD), end-stage
renal failure (ESRF) and after kidney transplantation,
that guidelines for revascularization of the general
population be adhered to (1D)

• revascularization of coronary arteries with coronary

artery bypass graft (CABG) and percutaneous
intervention (PCI) is associated with greater mortality
and morbidity in patients with CKD and those on
dialysis compared with the general population
 MEDICAL MANAGEMENT
Acute coronary syndrome

• CKD patients be treated as per the general

population when presenting with an acute
coronary syndrome (ACS)

• reperfusion therapy give preference to

primary percutaneous coronary intervention
over fibrinolysis
Chronic stable coronary artery disease
• eGFR) <60 mL/min, and specifically eGFR <30
mL/min undergoing antiplatelet or
anticoagulant therapy, at increased risk of
bleeding

• Dose adjustment of, specifically enoxaparin,

bivalirudin, and glycoprotein IIb/IIIa inhibitors
eptifibatide and tirofiban, is recommended
(1A)
• UFH may be used in place of LMWH eGFR ≤30
mL/min, with standardized monitoring of
clotting times (activated partial
thromboplastin time, APPT)

• stable cardiovascular disease single

antiplatelet agents (low dose aspirin,
dipyridamole, clopidogrel or ticlopidine) can
be used without an increased risk in major
bleeding events
• combination antiplatelet therapy with high-
dose aspirin (325 mg) and clopidogrel or
warfarin not be used in haemodialysis patients

• beta-blocker be prescribed for patients with

CKD (or kidney transplant) and heart failure
(1B)

• meet the criteria for an implantable

cardioversion/defibrillation device should be
considered for such devices (2C)
 HYPERTENSION
• Most blood pressure readings are below
140/90 (2D)

• most blood pressure readings should be below

130/80 in individuals with CKD and
macroalbuminuria (2B)
• Angiotensin-converting enzyme inhibitors or
ARB with proteinuria

• Diuretics, calcium channel blockers (CCB) and

betablockers may also be used
THANK YOU