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(Stroke. 2006;37:44.)
© 2006 American Heart Association, Inc.

Original Contributions

Lipid Testing and Lipid-Lowering Therapy in Hospitalized Ischemic Stroke and Transient Ischemic Attack Patients

Results From a Statewide Stroke Registry

Andrew J. Mullard, MS; Mathew J. Reeves, PhD; Bradley S. Jacobs, MD; Rashmi U. Kothari, MD; Gretchen L. Birbeck, MD; Kate Maddox, MS; Stacey Stoeckle-Roberts, MSN; Susan Wehner, MSN Paul Coverdell National Acute Stroke Registry Michigan Prototype Investigators

From the Department of Epidemiology (A.J.M., M.J.R., G.L.B., S.W.), Michigan State University, East Lansing, Mich; Department of Neurology (B.S.J.), Wayne State University School of Medicine, Detroit, Mich; Borgess Health System (R.U.K.), Kalamazoo, Mich; Department of Neurology and Ophthalmology (G.L.B., S.W.), Michigan State University, East Lansing, Mich; Department of Neurology (K.M.), University of Michigan, Ann Arbor, Mich; and Michigan Department of Community Health (S.S.-R.), Lansing, Mich.

Correspondence to Mathew Reeves, PhD, Department of Epidemiology, Michigan State University, B601 West Fee Hall, East Lansing, MI 48824. E-mail reevesm{at}msu.edu

	Abstract

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Background and Purpose— Recent recommendations call for in-hospital initiation of lipid-lowering therapy (LLT) for most ischemic stroke (IS) and transient ischemic attack (TIA) survivors; however, little is known about actual use. This study describes use of and predictors for in-hospital lipid testing and LLT using data from a statewide stroke registry.

Methods— In 2002, the registry ascertained cases from a stratified sample of 16 hospitals. This study includes only IS and TIA cases discharged alive.

Results— In 1907 study subjects, 30.2% (27.2% to 33.5%) were on LLT at admission. In 1399 subjects not on LLT at admission, 37.2% (30.2% to 44.9%) underwent lipid testing, and 12.9% (7.2% to 22.1%) received LLT at discharge. Use of testing and LLT varied widely between hospitals (P<0.001). In-hospital lipid testing was positively associated with large teaching hospitals (P=0.029), and neurologist or neurosurgeon (P=0.004); and negatively associated with increasing age (P=0.002), being female (P=0.020), a previous medical history of atrial fibrillation (P=0.002), nonambulatory status (P=0.005), and poor prognosis (P<0.001). LLT at discharge was positively associated with a previous medical history of dyslipidemia (P<0.001), lipid testing (P=0.004), and elevated low-density lipoprotein levels (P<0.001). Among subjects who were not on LLT at admission but who had Adult Treatment Panel III–based indications for use of LLT, only 31.2% (20.5% to 44.5%) received LLT at discharge.

Conclusions— Many hospitalized acute IS and TIA patients with indications for LLT are untreated at discharge. Efforts to close treatment gaps in lipid evaluation and treatment require sustained quality improvement efforts and should pay particular attention to high-risk patients.

Key Words: lipids • quality of health care • registries • stroke, acute

	Introduction

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Survivors of first-ever ischemic stroke (IS) and transient ischemic attack (TIA) often have generalized atherosclerosis,^1,2 and are at increased risk of morbidity and mortality from recurrent stroke and myocardial infarction.^3,4 The current American Heart Association (AHA) guidelines for the secondary prevention of stroke and TIA set treatment decisions based on the identification of multiple risk factors.² For lipid management, the goal is a low-density lipoprotein (LDL) level of <100 mg/dL.²

Treatment trials of statin drugs have shown that they reduce mortality in patients with coronary artery disease (CAD)^5–7 or acute coronary syndromes.^8,9 There is also increasing evidence for the value of statins in stroke survivors.^10,11 In the Heart Protection Study, major cardiovascular vascular events in patients who had a history of stroke or TIA but not CAD were reduced from 29.8% to 24.7% (P=0.001).^6,10 Also, meta-analyses have shown that the benefits of statin therapy for stroke prevention are independent of baseline lipid levels.¹² In 2004, this and other evidence led the AHA to advise in-hospital initiation of statin therapy for most first-ever IS and TIA patients of atherosclerotic origin regardless of LDL level.¹³

For hospitalized IS and TIA patients, the decision to use lipid-lowering therapy (LLT) involves the interpretation of available guidelines, as well as evaluation of a patient’s risk factors, contraindications, and acceptance. Studies of CAD patients have shown widespread undertreatment of dyslipidemia in hospital and primary care settings.^14,15 However, there is limited information on lipid evaluation and treatment among patients hospitalized for acute IS and TIA in the United States.

The objectives of this study were to use data from a statewide hospital-based stroke registry to describe the use of and predictors for in-hospital lipid testing and LLT at discharge among IS and TIA patients.

	Methods

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The Michigan Acute Stroke Care Overview and Treatment Surveillance System (MASCOTS) was a hospital-based prototype stroke registry for the Paul Coverdell National Acute Stroke Registry (PCNASR).^16,17 Stratified random sampling was used to select a single-stage cluster sample¹⁸ of 16 hospitals. The sampling frame consisted of all 114 Michigan hospitals that provided care to 30 stroke cases in 2000. Registry hospitals are representative of all hospitals providing acute care to >37 000 annual stroke discharges in the state. One of the hospitals closed after sampling and did not provide data. Human subjects approval was obtained from the institutional review board of each hospital before data collection.

Patients
Between May and November of 2002, trained study nurses prospectively ascertained all acute stroke admissions by monitoring emergency department admission logs, wards logs, and neurologic inpatient census and consultation lists. All patients 18 years of age who presented with a chief symptom or clinical signs and symptoms consistent with acute stroke and met 1 of 7 case definitions were enrolled into the registry (case definitions have been described previously).^16,17 This study includes cases with first-ever or recurrent IS, TIA, or IS of uncertain duration (ISUD) who were alive at discharge.

Data Collection
The MASCOTS data abstraction tool was an augmented version of the PCNASR core data elements.¹⁶ The abstraction tool included information on demographics, past medical history, medications at admission, results from the first in-hospital lipid test, in-hospital interventions, complications, and discharge plans including discharge medications.

Indications for LLT
To assess multiple risk factor–based indications for LLT at discharge, we applied the National Cholesterol Education Program (Adult Treatment Panel III [ATP III]) guidelines^1,19 to subjects who were not on LLT at admission but received in-hospital lipid testing. Subjects were classified as either "indeterminate" (if an LDL level was not documented despite testing), "not indicated," "optional," or "recommended."¹⁹ These classifications were approximated because systolic blood pressure was unavailable for use in calculating the Framingham Point Score. Instead, we substituted information on previous medical history of hypertension (ie, a hypertensive male scored 1 additional point whether treated or untreated, and a hypertensive female scored 1 additional point if untreated and 3 points if treated).¹⁹ We also evaluated the use of LLT at discharge based on the 1999 AHA treatment recommendations² of an LDL level <100 mg/dL.

Lipid Management
LLT at admission or discharge was defined as documentation that the patient was taking or had been prescribed any combination of statins, nicotinic acid, fibrates, or cholestyramine. In-hospital lipid testing was defined as a documented measurement during hospitalization of any combination of total cholesterol, subfractions (LDL cholesterol [LDL-C], high-density lipoprotein [HDL]-C), or triglycerides (TGs).

Predictors and Statistical Approach
Descriptive characteristics including weighted percentages and means (with 95% confidence limits) were calculated using SUDAAN software Release 9.0.1 (Research Triangle Institute). All statistical tests are ² unless indicated otherwise. This approach supports direct generalization of descriptive estimates to the statewide population.

Modeling to identify independent predictors for use of lipid testing and LLT were performed using SAS software version 9.1 (SAS Institute Inc.). Predictors were modeled in 2 stages. First, predictors were identified using multivariable logistic regression. All models included age, gender, and race as covariates of interest. Other predictors were identified using backward elimination procedures (with an of 0.30 for model entry and 0.05 to stay). Second, after final model predictors were identified, adjustment for potential hospital-level clustering was made by using generalized estimating equations to generate adjusted odds ratios with 95% confidence limits.²⁰ Modeling used unweighted data to circumvent problems encountered when performing complex modeling with weighted data.¹⁸

Analyses of in-hospital lipid testing and LLT at discharge included only subjects who were not on LLT at admission. The in-hospital lipid testing model tested stroke type (IS, TIA, or ISUD), health insurance, nursing home residence, previous medical history of stroke, myocardial infarction, coronary heart disease (CHD), atrial fibrillation, congestive heart failure, hypertension, and diabetes mellitus, and large teaching hospital (defined as hospitals that meet 2 of the following conditions: 325 licensed beds, 50 full-time equivalent interns and residents, or at least $3 million allocated to graduate medical education), neurologist or neurosurgeon (involved in care anytime during hospitalization), neurology attending service (defined as the attending service responsible for writing discharge instructions), stroke pathway use, in-hospital complications including pneumonia, urinary tract infection, and deep vein thrombosis (complications had to be symptomatic and require treatment but excluded pre-existing conditions), ambulatory status at admission, modified Rankin score at discharge, length of stay, and poor prognosis (defined by the treating physician as conditions that influenced care, such as do not resuscitate orders, comfort care only, or terminal illness; eg, metastatic cancer, severe stroke).

The LLT model evaluated all of the variables above plus 6 additional variables, including cerebrovasculature investigation (ie, carotid ultrasound, angiogram, or transcranial Doppler), echocardiography, in-hospital lipid testing, and lipid levels including LDL-C, HDL-C, and a composite of TGs and non-HDL.

	Results

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Study inclusion criteria were met by 1907 subjects. The mean age of study subjects was 72 years; 54.1% were female; and the racial distribution was 82.6% white, 10.5% black, and 6.9% other. The distribution of stroke type was 71.9% IS, 22.9% TIA, and 5.1% ISUD. Selected hospital and patient characteristics are provided in Table 1.

View this table: [in this window] [in a new window]   TABLE 1. Hospital and Patient Characteristics and Lipid Management in IS and TIA Patients Not on Lipid Medications at Admission at 15 Registry Hospitals (n=1399)

Among the 1907 subjects, LLT at admission was documented in 30.2% (27.2% to 33.5%), in-hospital lipid testing was performed on 38.8% (32.3% to 45.8%), and total LLT use at discharge was 36.1% (30.4% to 42.1%). Among 508 subjects on LLT at admission, 92.4% (89.4% to 94.6%) were on a statin drug, 42.5% (34.1% to 51.3%) underwent in-hospital lipid testing, and 89.5% (84.0% to 93.2%) continued pre-existing LLT at discharge.

Among the 1399 subjects not on LLT at admission, 37.2% (30.2% to 44.9%) underwent in-hospital lipid testing and 12.9% (7.2% to 22.1%) received newly initiated LLT at discharge. In those receiving therapy, 94.2% received a statin drug. Wide variation by hospital was found in the use of testing (0% to 90.9%; P<0.001) and LLT (0% to 88.6%; P<0.001; Table 1).

The final multivariable results identifying the significant predictors of in-hospital lipid testing and LLT at discharge are shown in Tables 2 and 3, respectively.

View this table: [in this window] [in a new window]   TABLE 2. Predictors of In-Hospital Lipid Testing in IS and TIA Patients Not on Lipid Medications at Admission (n=1399)

View this table: [in this window] [in a new window]   TABLE 3. Predictors of LLT at Discharge in IS and TIA Patients Not on Lipid Medications at Admission (n=1399)

Indications for LLT
In 650 subjects not on LLT at admission who underwent in-hospital lipid testing, the ATP III–based indications for use of LLT were classified as "indeterminate" in 12.4% (5.3% to 26.5%), "not indicated" in 54.2% (40.9% to 67.0%), "optional" in 14.0% (10.3% to 18.9%), and "recommended" in 19.3% (13.0% to 27.6%). Within these groups, the rate of newly initiated LLT at discharge was 12.8% (6.1% to 24.8%), 24.3% (17.7% to 32.4%), 31.5% (15.9% to 52.7%), and 31.2% (20.5% to 44.5%), respectively. In 521 subjects who were not on LLT at admission and had an LDL level recorded, 65.1% (56.5% to 72.8%) had an LDL level 100 mg/dL indicating the need for treatment based on the 1999 AHA recommendations.² Of these subjects, 31.3% (20.2% to 45.0%) received newly initiated LLT at discharge (Table 1). In subjects with an LDL level <100 mg/dL, 19.0% (15.6% to 23.0%) received newly initiated LLT at discharge.

	Discussion

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Our study demonstrated that lipid testing and treatment were underused as secondary preventive measures in a statewide sample of patients hospitalized with acute stroke or TIA. Whether a patient was treated with LLT or statins was strongly influenced by where he or she was treated but was also independently predicted by patient characteristics and patient care. These treatment gaps existed irrespective of which guidelines were applied. Only 31.3% of subjects who were eligible for treatment by the 1999 AHA recommendations² received newly initiated LLT at discharge. In subjects for whom use of LLT was recommended or optional by the 2001 ATP III guidelines,¹⁹ an almost identical proportion (31.2%) received newly initiated LLT at discharge.

According to the recent 2004 AHA recommendations, the majority of the patients in this study would have benefited from in-hospital initiation of a statin drug.¹³ However, among all the patients not on LLT at admission, only 12.9% actually received newly initiated LLT at discharge, and in the full study sample, only 36.1% (30.4% to 42.1%) were on LLT at discharge. Overall, up to about two thirds of all patients who might benefit from statins went untreated. This level of apparent undertreatment for use of LLT is similar to other studies of CHD and stroke patients.^8,21,22

We observed wide variation between hospitals in use of lipid testing and LLT at discharge; a previous study has reported similar findings.²¹ Although teaching hospital status independently predicted increased lipid testing, it did not predict use of LLT. Two of the 6 hospitals that had rates of newly initiated LLT <5% were large teaching hospitals (Table 1). We found that lipid testing increased with the involvement of a neurologist or neurosurgeon; similar associations have been reported previously.²³

Our findings that testing and LLT peaked among 50- to 69-year-olds and then declined with increasing age were similar to other studies.^21,24 Females were significantly less likely to receive in-hospital lipid testing, but we did not observe a significant association between gender and LLT at discharge. Other studies have reported that females have cholesterol measured less often and are treated less aggressively than men, but the causes of these differences are not clearly understood.²⁵ We initially found that compared with whites, blacks had a higher rate of in-hospital lipid testing and nearly equal rates of LLT treatment. However, after multivariable adjustment, there were no statistically significant racial differences in either model. Other studies, especially among cardiovascular disease patients, have reported that blacks receive less aggressive acute management and secondary preventive measures than do whites; however, evidence for racial disparities in stroke care is far less clear.²⁶

This study has several potentially important limitations. First, we did not record whether the discharge instructions included therapeutic lifestyle change, which could have been used instead of drug therapy as a first-line approach to dyslipidemia.²⁶ Second, the design of the registry did not allow monitoring for the use of lipid testing and LLT in the period immediately after discharge. Also, our approximation of the Framingham point score may have led to an underestimation of ATP III–based indications for LLT; however, we believe that this effect is likely to be small. Finally, we did not collect information on contraindications to LLT, which limited our ability to characterize the ideal target population for treatment.

In conclusion, our findings highlight the need to optimize lipid evaluation and LLT in hospitalized patients with stroke or TIA, particularly in high-risk patients for whom established guidelines already exist but are inadequately followed. The gaps in the evaluation and treatment of dyslipidemia are best addressed by the use of quality improvement programs, such as Get with the Guidelines—Stroke,²⁷ that monitor performance and provide a process for quality improvement.

	Acknowledgments

 
This study was supported by US Centers for Disease Control and Prevention Cooperative Agreement No. U50/CCU520272-01. Many thanks to participating institutions and providers: Spectrum Health Systems, Grand Rapids, Mich (Herman Sullivan, MD; Wendy Arntz, RN; Carmen Noorman, RN); St. Joseph Mercy Hospital, Ann Arbor, Mich (Rodney Smith, MD; Shirley Frederiksen, RN, MS); University of Michigan Hospital, Ann Arbor (Susan Hickenbottom, MD; Kate Maddox, MS, RNC); Borgess Medical Center, Kalamazoo, Mich (Karen McShane, RN, BSN; Brianna Stokes, RN); Sparrow Health Systems, Lansing, Mich (Arshad Majid, MD; Mary Lou Mitchell, RN, MSN); Ingham Regional Medical Center, Lansing, Mich (Sid Shah, MD; Christine Bossenbery, RN); Detroit Receiving Hospital, Michigan (Julie Klinker, RN, BSN); Henry Ford Wyandotte Hospital; St. Joseph Mercy of Macomb (Angela Kavanagh, RN, MSN; Susan Wesson, RN); Northern Michigan Regional Health System, Petoskey, Mich (Steven Huder, MD; Elaine Siwiec, RN, BSN); St. Mary’s Hospital, Saginaw, Mich (Faith Abbott, DO; Richard Herm, BSN; Kristin Leedom, MSN); Bronson Methodist Hospital, Kalamazoo, Mich (Jennifer Brown, RN, BSN; Denise Robinson, RN, MSN); Harper University Hospital, Detroit, Mich (Julie Klinker, RN, BSN); Alpena General Hospital (Cheryl Parsons, MD; Terry Zaborney, RHIT; Mary Jo Skiba, RN); and St. Joseph Health Systems, Tawas, Mich (William Rosenfeld, MD; Pat McDougall, RN, BSN).

Received September 22, 2005; accepted October 13, 2005.

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This Article Abstract Full Text (PDF) All Versions of this Article: 37/1/44    most recent 01.STR.0000195127.12990.43v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mullard, A. J. Search for Related Content PubMed PubMed Citation Articles by Mullard, A. J.