Marrs JC.

Am J Manag Care. 2011 Dec;17 Suppl 16:S403-11.

Abstract

Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease (CVD). Often, CKD and CVD coexist, and patients warrant optimal pharmacotherapy to reduce the risk of future cardiovascular (CV) events. Randomized trials have evaluated the role of antihypertensive therapy and lipid-lowering therapy as means to reduce CVD in patients with CKD. Many clinical trials support the role of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the CKD population. In addition, many clinical trials have evaluated the role of statin therapy in reducing CV events in early- and late-stage CKD. The struggle with interpreting results from these trials is that there are a number of different CV composite end points and a lack of consistency in defining CKD, especially in some post hoc subanalyses. Overall, ACEI/ARB therapy is supported by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) hypertension guidelines and statin therapy is supported by the Adult Treatment Panel (ATP) III and NKF KDOQI dyslipidemia guidelines to optimally manage patients with CKD and CV risk factors. Questions remain as to the optimal role of statin therapy in patients with CKD receiving dialysis. JNC 8 and ATP IV guidelines will be available in the next year, and it is expected that there will be specific recommendations on both hypertension and dyslipidemia management in the CKD population.

Background

Chronic Kidney Disease (CKD) is an independent risk factor for developing cardiovascular disease [1]. Other cardiovascular risk factors, such as diabetes, hypertension, and dyslipidemia, are also highly prevalent in patients with CKD [1]. CKD is defined as kidney damage for more than 3 months, as confirmed by biopsy or markers of damage (e.g. microalbuminuria with or without a decrease in glomerular filtration rate (GFR) or GFR< 60 ml/min/1.73 m2 for > 3 months [1]. Patients with end-stage renal disease (ESRD) have a mortality rate due to cardiovascular diseases 10 to 30 times higher than the general population [2,3].
As traditional cardiovascular risk factors often occur in the CKD population, they are important therapeutic targets [4,5]. Also other risk factors (such as high homocysteine levels) are associated with higher CVD risk in patients with CDK [6].
This review article evaluates evidence from clinical trials supporting antihypertensive and lipid-lowering therapy in the CKD population to prevent CV outcomes.

Most important messages

Among antihypertensives, ACEI and ARB have the most prospective data on CV outcome benefit in CKD patients, also for other reasons than preventing CV events (e.g., delaying progression of nephropathy). Table 1 summarizes US blood pressure goals and treatment recommendations for patients with CKD [7-9].

	NKF KDOQI	JNC 7	AHA
	2003	2003	2007
Lifestyle modifications	All	All	All
ACI or ARB preferred	Diabetic kidney disease Nondiabetic kidney disease With spot protein-to-creatinine ratio ≥ 200 mg/g	All	1st line option in addition to calcium channel blocker or thiazide
BP goals	< 130/80 mm Hg Lower if spot protein-to-creatinine ratio 500-1000 mg/g	< 130/80 mm Hg	< 130/80 mm Hg

ACEI indicates angiotensin-converting enzyme inhibitor; AHA, American Heart Association; ARB, angiotensin receptor blocker; BP, blood pressure; JNC 7, Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; NKF KDOQI, National Kidney Foundation Kidney Disease Outcomes Quality Initiative.
aLifestyle modifications include weight reduction, Dietary Approaches to Stop Hypertension (DASH) diet, dietary sodium restriction, physical activity, and moderation of alcohol consumption.Many people with CKD are not on their target blood pressure goal or on ACEI or ARB therapy, which is alarming as optimal blood pressure management leads to many cardiovascular and non-cardiovascular benefits.

Statin therapy reduces CV events in a broad range of patients, from early CKD to post kidney transplant, especially in patients not requiring dialysis. Table 2 shows guidelines for managing dyslipidemia in CKD [10].

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Lipid abnormality	Goal	Initial therapy	Secondary therapy	Alternative therapy
TG≥500 mg/dL	TG < 500 mg/dL	TLC	TLC + fibrate or niacin	Fibrate or niacin
LDL-C 100-129 mg/dL	LDL-C < 100 mg/dL	TLC	TLC + low-dose statin	Bile acid sequestrant or niacin
LDL-C ≥ 130 mg/dL	LDL-C < 100 mg/dL	TLC + low-dose statin	TLC + maximum-dose statin	Bile acid sequestrant or niacin
TG ≥ 200 mg/dL and non-HDL-C ≥ 130 mg/dL	non-HDL-C < 130 mg/dL	TLC + low-dose statin	TLC + maximum-dose statin	Fibrate or niacin

HDL-C indicates high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglyceride; TLC, therapeutic lifestyle changes.

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Benefits in CKD patients can occur by targeting a lower LDL-C level than US guidelines currently recommend, which was also shown in the SHARP study, supporting the potential for a more aggressive LDL-C target in the CKD population [11].
In the recently published ESC/EAS guidelines on the management of dyslipidemia, patients with CHK are considered at very high risk of CV events; an LDL-C goal < 70 mg/dL is recommended [12].

Conclusion

Antihypertensive therapy and statin therapy significantly reduce major CV events in patients with CKD with or without established CVD. New guidelines will contain specific recommendations on hypertension and dyslipidemia management in the CKD population.

References

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