Cardiovascular Diseases after Solid Organ Transplantation

Jae-Joong Kim

doi:10.4285/jkstn.2011.25.4.229

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Kim: Cardiovascular Diseases after Solid Organ Transplantation

Review Article

J Korean Soc Transplant 2011;25(4):229-238.

Published online: 10 January 2011

DOI: https://doi.org/10.4285/jkstn.2011.25.4.229

Cardiovascular Diseases after Solid Organ Transplantation

Jae-Joong Kim, Ph.D.

¹Department of Internal Medicine, Asan Heart Institute, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

책임저자：김재중, 서울시 송파구 올림픽로 43길 88울산대학교 의과대학 서울아산병원 내과, 138-736 Tel: 02-3010-3154, Fax: 02-486-5918 E-mail: jjkim@amc.seoul.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Despite recent advances in the prolongation of patient and graft survival, transplant patients continue to die prematurely of cardiovascular disease. Cardiovascular disease after solid organ transplantation is a serious complication caused by numerous factors, most shared with the general population and others specific to transplant recipients including immunosuppressive drugs and renal dysfunction. Among traditional risk factors in general population, hypertension, dyslipidemia and diabetes are more common in solid organ transplant recipients. The control of risk factors is more difficult in transplant recipients than in general population. Immunosuppressive drugs are related to hypertension, dyslipidemia and posttransplant DM. Reduction of immunosuppression is helpful to reduce the risk of cardiovascular disease but may increase the risk of rejection and graft loss. mTOR inhibitor has less potential risk to develop cardiovascular disease. Future development of new immunosuppressive drug with less potential risk of CV disease but same efficacy to prevent rejection and graft loss will be a promising goal to prevent CV disease. In conclusion, multidisciplinary approach that emphasizes evidence-based management of traditional risk factors and development of new immunosuppressive drugs are the best approach to reducing the risk of CV disease after solid organ transplantation.

Keywords: Solid organ transplantation, Cardiovascular diseases, Risk factors

References

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Table 1.

Prevalence of new posttransplant cardiovascular events

Type	Prevalence (%)
Ischemic heart disease	11.2
Chronic heart failure Peripheral vascular disease	7.2 8.5
Cerebral vascular disease	4.6

Table 2.

Cardiovascular risk factors in general population

Major independent risk factors	Other risk factors
Major independent risk factors	Predisposing	Conditional
Cigarette smoking	Obesityab ^a,b	Elevated serum triglycerides
High blood pressure	Abdominal obesity ^c	Small LDL particles
Elevated serum total (and LDL) cholesterol	Physical inactivity ^a	Elevated serum homocysteine
Low serum HDL cholesterol	Family history of premature coronary heart disease	Elevated serum LP (a)
Diabetes mellitus	Ethnic characteristics	Prothrombotic factors (e.g., fibrinogen)
Advancing age	Psychosocial factors	Inflammatory markers (e.g., G-reactive protein)

^a Defined as major risk factors by the American heart Association;

^b Defined by body mass index as follows: normal weight, 18.5 to 24.9 kg/m²; overweight, 25 to 29 kg/m²; obese, greater than 30 kg/m² (obesity class I, 30.0 to 34.9 kg/m²; class II, 35.9 to 39.9 kg/m²; class III, ≥40 kg/m²);

^c Defined according to waist circumference: men, greater than 102 cm (＞40 in.); women, greater than 88 cm (＞35 in.).

Table 3.

Cardiovascular risk factors in renal transplant recipients and relative risks

	Relative risk (95% CI)
Male	2.09 (1.33∼3.27)
Underlying CV disease	3.27 (2.22∼5.35)
Nephrosclerosis	2.88 (1.6∼5.05)
Posttransplant hypertension	1.7 (1.12∼2.7)
Reduced renal function (GFR ＜60 mL/min)	1.4 (1.01∼2.14)
Persistent proteinuria	2.4 (1.66∼3.62)
Posttransplant DM	2.09 (1.29∼3.39)

Table 4.

Prevalence of traditional cardiovascular risk factors in ESRD patients groups (%)

Risk factors	Dialysis patient	Transplant candidate	Transplant recipient
Hypertension	80	75	80
DM	40	35	55
Hypercholesterolemia	25	25	60
Obesity (BMI ＞30)	14	20	32
Cigarette smoking	18	24	20
LV hypertrophy	75	75	52
Anemia (Hct ＜30%)	32	25	40

Table 5.

Mechanisms that contribute to posttransplant hypertension

1. Pretransplantation factors

– Increased vascular stiffness

– Vascular calcification

2. Posttransplantation factors

– Hypervolemia

– Immunosuppressive drugs

: corticosteroid, calcineurin inhibitors

In Kidney transplantation

– TRAS (transplant renal artery stenosis)

– Delayed allograft function

– Poor allograft function

– Proteinuria

– Presence of native kidney

Table 6.

Different mechanisms of calcineurin inhibitor induced rise of BP

1. Systemic vasoconstriction

– Imbalance between vasoconstrictive and vasodilators

– Increase in vasoconstrictive substance:

endothelin-1, thromboxane A2

– Decrease in vasodilator compounds: prostacyclin and NO

– Increase in intrarenal rein activity

– Accentuation of angiotensin II action

– Increase in sympathetic nervous activity

2. Effect on the kidney

– GFR reduction

– Increase in tubular sodium reabsorption

Table 7.

Antihypertensive medications commonly used in transplant recipients and their potential adverse effects

Class of drug	Features	Adverse effects
Calcium channel blockers Dihydropyridines	Potent vasodilators antagonize CNI-mediated vasoconstriction	Edema, headache, gingival hyperplasia, tachycardia
Nifedipine XL	Rapid onset of action
Amlodipine	Steady state reached 7∼8 d from drug initiation Long half-life (35 h)
Nondihydropyridines
Diltiazem	Moderate potency	Bradycardia, edema
Verapamil	Least potent	Constipation, bradycardia
Beta-blockers	Less potent antihypertensive, may diminish	Bradycardia, bronchospasm, potential for
Atenolol, metoprolol	CNI-related headache	rebound tachycardia
α-β-Blockers	Effective antihypertensives, rapid onset, and short	Bradycardia, postural hypotension dizziness,
labetalol	duration of action	rebound hypertension
	Multiple daily dosing is required
ACE-inhibitors	Limited efficacy and short duration with enalapril	Hyperkalemia, non-anion gap metabolic
Enalapril, lisinopril, ramipril	No clear benefit from starting early after	acidosis, azotemia
ARBs	transplantation
Valsartan, losartan
Diuretics	Especially useful in proteinuric patients
Thiazides	Potentiate other antihypertwnsive medications	Prerenal azotemia, electrolyte abnormalities
Loop	Effective in volume-dependent hypertension
Spironolactone	Spironolactone might have renal protective effects

Table 8.

Treatment guidelines for posttransplant dyslipidemia

Do
Treat all patients with LDL ＞100 mg/dL
Treat non-HDL-C ＞130 mg/dL if triglycerides are ＞200 mg/dL
Use diet and a statin as initial therapy
Use additional measures if LDL ＞130 mg/dL and the patient is at high risk
Do not
Stop the statin if the goal is not achieved
Use a statin+a fibrate
Use a high dose of a statin+CsA
Use a statin+CsA+an azole antifungal agent
Use a statin+CsA+a macrolide antibiotic
Use a statin+CsA+a high dose of a nondihydropyridine calcium antagonist

Table 9.

Effects of immunosuppressive agents on cardiovascular risks

Drug	Dyslipidemia	Diabetes	Hypertension	Renal dysfunction
Corticosteroids	↑ ↑	↑ ↑	↑ ↑	–^a
Cyclosporine	↑ ↑	↑	↑ ↑	↑ ↑
Tacrolimus	–	↑ ↑	↑	↑ ↑
Sirolimus	↑ ↑	–	–	↑ (?)
Mycophenolate	–	–	–	–
mofetil
Azathioprine	–	–	–	–

^a –, has no known effect on the incidence and/or severity of the risk factor.

Table 10.

Control of cardiovascular risk factors

Treatable CVD risk factors	Primary prevention
Hypertension	Antihypertensive agents; use of angiotensin-converting enzyme (ACE) inhibitors is suggested
Elevated total or LDL	Lipid-lowering diets and drugs; use of statins is suggested
Cholesterol; reduced HDL
Cholesterol; elevated triglycerides
Diabetes	Tight glycemic contol
	Tobacco use cessation (counseling, nicotine replacement therapy)
Physical inactivity	Exercise (moderate level of physical activity for 30 minutes most days of the week)
CMV infection	Antiviral agents (ganciclovir etc.)
Hyperparathyroidism	Calcium channel blockers
Proteinuria	ACE inhibitor
Elevated creatinine	Immunosuppressive therapy, dialysis

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