Cholesterol screening in children : an assessment of primary care physicians' practice

Transcription

1 The University of Toledo The University of Toledo Digital Repository Master s and Doctoral Projects Cholesterol screening in children : an assessment of primary care physicians' practice Susan Lynn Nichols Medical University of Ohio Follow this and additional works at: This Scholarly Project is brought to you for free and open access by The University of Toledo Digital Repository. It has been accepted for inclusion in Master s and Doctoral Projects by an authorized administrator of The University of Toledo Digital Repository. For more information, please see the repository's About page.

2 FINAL APPROVAL OF SCHOLARLY PROJECT Master of Science in Biomedical Sciences Concentration in Physician Assistant Studies Cholesterol Screening in Children: An Assessment of Primary Care Physicians Practice Submitted by Susan Nichols In partial fulfillment of the requirements for the degree of Master of Science in Biomedical Sciences Date of Presentation: December 15, 2005 Academic Advisory Committee Major Advisor Martin Keck, M.Ed., MHS, PA Department Chairperson Patricia Hogue, M.S., PA-C Dean, College of Health Sciences Christopher E. Bork, Ph.D., P.T. Dean, College of Graduate Studies Keith K. Schlender, Ph.D.

3 Cholesterol screening in children: An assessment of primary care physicians practice Susan Lynn Nichols, PA-SIII Medical University of Ohio at Toledo 2005

4 ii Acknowledgments I want to say thank you to all of the hardworking faculty and staff of the Physician Assistant program at the Medical University of Ohio. I want to specifically thank Professor Keck, Dean Bork, and Chair Hogue for helping me in times of need for project organization and data analysis. I also want to thank the MUO Family Practice Center for their time and efforts in this research project.

5 iii Table of Contents I Introduction...1 II III IV Literature Review...4 Methodology...24 Results...27 V Discussion and Conclusions...30 References...36 Appendices...39 A. Definitions of Terms...39 B. Data Collection Tool...40 C. Tables and Figures...41 Abstract...50

6 1 Chapter I - Introduction Heart disease is the leading cause of death in the United States, with over 500,000 deaths each year (Brown, 2001) and 15 million deaths worldwide annually. Elevated blood cholesterol has been proven to be one of the risk factors linked to cardiovascular disease and atherosclerosis along with the associated morbidity and mortality (O Loughlin et al, 2004). The fact that so many people die each year due to heart disease does not come as a surprise since as many as one out of every five US adults are in need of therapy for their elevated cholesterol levels (Brown). Among the people that are being affected by acute coronary heart disease, 20% are patients 55 years old and younger. Many of these adults that are suffering from premature disease may have children with heart disease risk factors that need attention (Lauer et al, 1992). The value of lowering cholesterol in adults was first addressed in 1988 when the National Cholesterol Education Program (NCEP) published it s first report on recommendations for lowering elevated cholesterol in people 20 years of age or older. In the NCEP II report, published in 1991, there was a separate section on cholesterol levels in children and adolescents. This report emphasized the importance of early detection of elevated cholesterol in children and adolescents, since high levels early in life lead to atherosclerosis and an elevated risk for heart disease as adults. The mean total cholesterol for children and adolescents (between the ages of 4 and 19) in the United States is around 165 mg/dl and the mean low-density lipoprotein (LDL) is around 96 mg/dl (American Heart Association, 2005). Both of these values are around the 75 th percentile worldwide, which shows that US children and adolescents have higher blood cholesterol levels compared to other countries. Acceptable levels of cholesterol in children and adolescents are under 170 mg/dl for total cholesterol and under 100 mg/dl for LDL levels (Lauer et al). Both of the national cholesterol averages are very close to the acceptable

7 2 guidelines, showing that there are indeed many individuals that surpass these specific values. Special attention is needed regarding this issue, so that we can cut down on annual deaths and millions of health care dollars that are spent on a disease that is preventable if detected at early stages (McGill et al, 2000). It was noted in research that, A 10 percent decrease in total cholesterol levels may result in an estimated 30 percent reduction in the incidence of coronary heart disease (Cohen, 1997). The question posed was; was there a disparity in cholesterol screening of high risk children and adolescents at the Family Practice Center (FPC) in Toledo, Ohio when compared to NCEP and their report from 1991? There has been conclusive research showing that atherosclerosis, high blood cholesterol and other risk factors found in childhood and adolescence correlate to acquiring heart disease as an adult (McGill et al, 2000). Despite this evidence, many health care workers fail to screen high risk children and adolescents for elevated total cholesterol. The purpose of this study was to evaluate the physicians at the FPC and their practice of screening high risk children and adolescents for elevated blood cholesterol. Specifically, the study was focused on a well-defined population of high risk children and adolescents between the ages of 2-19 to determine the percentage of those children screened. A second goal was to examine whether the physicians were implementing the NCEP, American Academy of Pediatrics (AAP), or the American Heart Association (AHA) guidelines for testing and cholesterol management. The results of this study may assist health care providers to identify practice behaviors that may be inconsistent with national guidelines.

8 3 Chapter II - Literature Review When learning about cholesterol levels within the bloodstream, it is important to be aware of the differences between lipids, lipoproteins, and cholesterol itself. Many people are not aware of these differences, and thus may interpret data making false assumptions. Lipids are the precursors to all the different kinds of fat within plants and animals. Microscopically they are spherical layers of oil that are made up of cholesterol, proteins, phospholipids and triglycerides. The major role of lipids within our system is to serve as a source of energy to carry out cellular functions. Cholesterol is a soft, waxy lipid that is found in many tissues as well as undissolved in the bloodstream (Kennard, 2004). Although many people believe cholesterol has only negative consequences, this nutrient serves many vital functions within the human body as well. Cholesterol is involved in the synthesis of vitamin D on the surface of the skin, repairs many cell membranes, and produces the sex hormones estrogen and testosterone. Triglycerides are also found undissolved in the bloodstream since they are waterinsoluble. These molecules act as carriers of fatty acids in both the blood and tissues and are composed of three fatty acids and a glycerol component. Lipoproteins are spherical protein complexes that transport cholesterol, triglycerides, and other lipid molecules throughout the bloodstream (Lauer et al, 1992). There are five major types of lipoproteins which are classified into groups depending on size, density, and type of molecule carried (cholesterol or triglycerides). The two lipoproteins that carry cholesterol are high-density lipoprotein (HDL), which is the smallest and most dense and low density lipoprotein (LDL). Intermediate density lipoproteins (IDL), very low density lipoproteins (VLDL), and chylomicrons (largest) all carry triglycerides (Nidus, 2001).

9 4 Another important aspect of understanding cholesterol lies within the cycle of synthesis, transport, and excretion of this lipid complex. Cholesterol accumulates in the body by the sources of dietary intake or biosynthesis within the liver, intestines, and endoplasmic reticulum or cytosol of nucleated cells (Murray, Granny, Mayes, and Rodwell, 2000). Of this total cholesterol, only 50% is absorbed into the bloodstream, while the remaining is eliminated in the stool (Repka, 2004). The biosynthesis of this molecule is a complex five-stage process, with the precursor always being two molecules of acetyl-coa. An important rate-limiting step in the biosynthesis process involves the enzyme HMG-CoA reductase, which decreases in activity when fasting occurs and therefore reduces cholesterol synthesis. This enzyme plays a key role in the most effective cholesterol lowering therapy (HMG-CoA reductase inhibitors), which will be discussed in a later management section. Cholesterol transportation occurs in lipoproteins of the plasma, with the majority found in LDL. With LDL, it either travels to the LDL receptors found on the liver or to peripheral tissue. Once the LDL enters a cell (liver tissue or peripheral tissue) the lipoprotein is destroyed but the cholesterol remains. To transport cholesterol into the plasma, VLDL ships out triglycerides and cholesterol from the liver. The triglycerides are disassembled by lipoprotein lipase to form fatty acids so they are able to reform within muscle or fat cells (Repka, 2004). The majority of the cholesterol remains in the remnant of VLDL, which is IDL, and further taken up by the liver or transformed into LDL (Murray, Granny, Mayes, and Rodwell, 2000). Cholesterol elimination is constantly occurring at the rate of one gram per day. After conversion to bile acids in the liver, fifty percent of the total cholesterol is excreted through the intestines in the stool. The remaining portion is eliminated unchanged, with most entering enterohepatic circulation and being reabsorbed into the body. Upon entering the digestive tract,

10 5 cholesterol is mainly reabsorbed in the first portion of the small intestine (duodenum), while bile acids are absorbed in the last portion (ileum). Enterohepatic circulation involves the bile acids (salts) returning to the liver via portal circulation, with only a small amount (400 mg/d) actually bypassing reabsorption and being eliminated in the feces. This pathway remains to be a major source of cholesterol elimination however, since the enterohepatic cycling is so efficient that these bile acids are traveling through the intestines six to ten times every single day (Murray, Granny, Mayes, and Rodwell, 2000). Although all of the processes just discussed are very complex, it is important to gather a rudimentary background to better comprehend the mechanisms by which this molecule acts in our body. Without this general knowledge, it is hard to appreciate the need for special care regarding cholesterol levels, and the consequences of this delayed understanding may make the difference in patients lives. The major concern regarding elevated cholesterol levels deals with the fact that heart disease remains to be the number one killer among women and men in the United States. It has been found that elevated cholesterol levels are a strong risk factor for developing this disease, and over 90 million adults in the United States (close to 50%) have elevated levels (Henkel, 1999). This is clearly a problem that needs to be tackled to prevent millions of people from suffering due to angina, heart attacks, and even death. The following will discuss cholesterol s roles in the development of atherosclerosis in children and adolescents and eventually coronary heart disease as adults. The pathophysiology of atherosclerosis begins with, the deposition of cholesterol in the connective tissue of arterial walls (Murray, Granny, Mayes, and Rodwell, 2000). When looking at the cholesterol panel, the important factors to analyze are the LDL as well as the LDL: HDL cholesterol ratio, when concerned about atherosclerotic changes. High levels of LDL and low

11 6 levels of HDL both indicate a more negative prognosis, based on the roles these lipoproteins play in cholesterol transport. As stated before, LDL acts as a transporter to tissues while HDL behaves as a reverse transporter in which cholesterol is carried to the liver (Murray, Granny, Mayes, and Rodwell). This understanding of cholesterol transportation correlates to the general public knowledge that LDL behaves as the bad cholesterol and HDL the good cholesterol. When looking at the pathophysiology of atherosclerosis it is also important to understand the difference between early and advanced lesions. A report from the AHA was published in 1994 and discusses the definitions of initial, fatty streak, and intermediate lesions of atheresclerosis. It is vital to understand the differences in lesions since advanced lesions more commonly produce clinical symptoms while the early lesions usually continue growing unnoticed with no clinical manifestations. Lesions are differentiated into five distinct groups with type I being the earliest lesion and type V being the most advanced. The lesions of interest when discussing childhood and adolescence will predominantly be of type I and II, where type III may appear in young adulthood (Stary et al, 1994). There are multiple hypotheses regarding initiation of atherosclerotic lesion formation, with the fundamental one being the build up of plasma lipoproteins within the arterial walls starting a cascade of cellular reactions. As more lipoproteins accumulate the lesion grows in both size and advancement. Other molecules that may add to the amount of accumulation within the arteries are apoproteins A and B and macrophage foam cells. As stated in this AHA special report, it was found that a high cholesterol diet in lab animals led to the formation of lesions that resembled human atherosclerotic lesions of type I and II. Another common hypothesis is the response-to-injury theory, which involves migration and proliferation of smooth muscle cells into the lumen of the artery in response to cellular damage. This endothelial damage may initiate

12 7 the thickening of the lumen by releasing cytokines, which act as cell messengers by attracting leukocytes and smooth muscle cells to the area of damage. Other theories include initiations of lesions due to fibrin and/or platelet deposits or gelatinous thickening with few cell types present (Stary et al, 1994). Although there are five different classifications of lesions according to research, only the first three types will be discussed since these predominate in children and youth. Type I lesions are the first deposits in the arterial wall (intima) and the cellular reactions that correspond to these lipid complexes. These are commonly referred to as initial lesions and are most frequently found in infancy and childhood. Many of these lesions are too small to be seen without microscopic examination, and when viewed microscopically they may only appear as yellow colored dots on the intimal surface. The cellular reactions occurring involve macrophages with droplets of lipids, which are known as macrophage foam cells (Stary et al, 1994). Type II lesions are usually classified as fatty streaks, which are visible without a microscope and resemble yellow colored streaks, spots, or patches on the arterial wall. However, not all type II lesions are fatty streaks therefore the classification of type II is determined by microscopic criteria. In contrast to type I, type II lesions have layers of macrophage foam cells instead of only scattered groups. Lipid deposits begin to be seen in smooth muscle cells as well as in macrophages, and additional cell types such as T lymphoctyes and mast cells are found within these lesions as well. Lipids present in type II lesions are composed of cholesterol esters (77%), phospholipids, and cholesterol itself. Within the type II classification there are two subsets called IIa and IIb based on the ability of the lesion to progress to advanced stages. The type IIa lesions are also called progression (or advanced)-prone and are generally located in areas

13 8 where type I lesions are highly rich in foam cells. Type IIb lesions, called progression (or advanced) lesion-resistant, are more common of the two subsets and found in arterial walls which contain a small number of smooth muscle cells and are therefore very thin. Whether or not a lesion is prone or resistant to advancement depends on mechanical forces, such as low shear stress which causes an increase in interaction time between cholesterol molecules and the intimal surface. It was noted that 99% of children between the ages of 2-15 had type II lesions in the aorta, and lesions did not start developing in the coronary arteries until around the time of puberty (Stary et al, 1994). Type III lesions are known as intermediate lesions and provide the link between initial lesions and fatty streaks, and to those of more advanced stages such as the atheroma (type IV). Histologically these lesions contain lipid droplets in extracellular spacing and large amounts of lipid are found within the smooth muscle layers, which start to disrupt the arterial walls. These lesions also contain more free tryglycerides, cholesterol, and fatty acids when compared to type II lesions (Stary et al, 1994). A study done in the year 2000 focused on autopsy data of 2876 subjects between the time of June 1987 and August The subjects were people between the ages of 15 and 34 who were autopsied within 48 hours of death by accidents, suicides, or homicides. The purpose of doing this research was to find how many of these subjects had atherosclerotic lesions called fatty streaks (type II) typical in childhood and adolescence. This lesion is generally, not elevated above the intimal surface and contains predominantly foam cells of mononuclear or smooth muscle cell origin with minimal extracellular lipid or connective tissue (McGill et al, 2000). However, in late adolescence and early adulthood these lesions become raised and are classified as fatty plaques or raised fatty streaks, which contain lipid within the foam cells. The

14 9 purpose of looking for these fatty streaks was the fact that there is a relationship between their existence and having Coronary Heart Disease (CHD) risk factors. The results showed that risk factors seem to accelerate the process of atherosclerosis on raised fatty streaks as early as the age of 15 and maybe even earlier. Risk factors included in this study were high non-hdl cholesterol, low HDL cholesterol, smoking, hypertension, obesity, and impaired glucose tolerance (McGill et al). From these results, it is evident that the prevention of this process should start well before mid-adolescence. Another related study gathering data from 1979 to 1988 also looked at coronary arteries and aortas in people who had died at premature ages (birth to 39 years) from accidents, suicides, or homicides. This sample originally contained 1286 subjects, but later was refined to 691 because of the shorter times between death and autopsy. The results showed that there were signs of type I and/or type II lesions as early as the age of 1 year. It was noted that there was a relatively large increase in lesions found between the 5-9 age range and the age range. Only 21% of the coronary arteries inspected in 5-9 year olds had early lesions, while at years 54% had some form of a lesion. It was also striking that by the age of 39, 95% of the population has some form of a lesion. The results showed that after puberty, there was an increase in the later lesions (type III, IV, and V) when compared to before puberty, and a decrease in early lesions type I and II. This represents the fact that advanced lesions may indeed progress from early lesions noted in early childhood (Stary, 1990). The importance of all the above discussion mainly deals with the cardiovascular health of children and selective cholesterol screening in high-risk populations. Throughout the years there have been numerous guidelines regarding cholesterol levels in adults, but little knowledge about specific goals for children and adolescents. The NCEP, which is coordinated by the National

15 10 Heart, Lung, and Blood Institute (NHLBI) has issued three major guidelines for adults and clinical practice throughout the years. The first NCEP guidelines were issued in 1988, the second in 1993, and the latest includes the report of the Adult Treatment Panel III (ATP III) published in The guidelines discuss treatment, cholesterol measurement, and dietary/pharmocologic treatment (NHLBI, 2001) for adults. In addition to these three guidelines, the NCEP has issued an expert panel on blood cholesterol levels in children and adolescents in 1991 due to the increasing knowledge of atherosclerosis beginning in childhood (Lauer et al, 1992). The following discussion will explain the NCEP report on blood cholesterol levels in children and adolescents of 1991, and also explain other studies that have also reported similar findings. As seen from the above discussion on cholesterol and atherosclerosis, there is much evidence that these processes begin early in childhood and may lead to CHD as an adult. Although there has been a recent decline in the morbidity and mortality of this disease there are still 500,000 deaths each year. Even more striking is the fact that they reported 20% of hospital discharges for CHD were in patients under the age of 55 years, which speaks highly of the importance of lipid screening in children and adolescents. Numerous epidemiologic studies have been done that clearly link high levels of cholesterol as a major risk factor of CHD, with approximately each one-percent rise in cholesterol causing the CHD risk to rise by two-percent. Not only this, but the Coronary Primary Prevention Trial (CPPT) has shown that managing the hyperlipidemia pharmacologically actually causes the risk factor of CHD to decrease by 50% when total cholesterol was reduced by over 25% of original high lipid level. Since there has been a notable difference in mortality due to intervention, the NCEP has set for guidelines for screening children and adolescents (Lauer et al, 1992).

16 11 The recommendations for selective screening based on the panel deal with children and adolescents aged 2-19 years who may become adults at risk for CHD due to elevated cholesterol levels that progress into adulthood. The first criterion revolves around children and adolescents who have parents and/or grandparents who were found to have atherosclerosis before the age of 55. This includes adults who underwent coronary arteriography, balloon angioplasty, or coronary artery bypass surgery. Other associated conditions of concern that warrant screening with premature onset in relatives include a myocardial infarction, peripheral vascular disease, angina pectoris, cerebrovascular disease, or an abrupt cardiac event causing death. All of the mentioned are often compiled into one group as being a positive family history of cardiac disease. The second major category of screening includes children or adolescents who have either one of their parents with a total blood cholesterol of 240 mg/dl or higher. Some children and adolescents that do not have a family history documented will still be screened due to other risk factors present that may incline the clinician to override the two criteria and screen based on their clinical judgement (Lauer et al, 1992). In addition, if and when the child or adolescent is tested, there entails criteria for which further evaluation is needed. The NCEP panel has reached the decision that total cholesterol of greater than 200 mg/dl or LDL cholesterol of greater than 130 mg/dl in children and adolescents which meet the above criteria warrants further investigation of dietary and or pharmocologic treatment with follow-up. Borderline values range from mg/dl total cholesterol and mg/dl LDL cholesterol. The rationale behind these two recommendations have been made based on numerous studies that have linked elevated lipid or lipoprotein levels in children and adolescents with increased levels as adults. The next important aspect of this research involves knowing national data regarding averages of cholesterol values of children and adolescents, as well as how many children would

17 12 actually be classified as having borderline and/or elevated lipid levels. The Lipid Research Clinics (LRC) Prevalence Study was one in particular that actually showed a correlation between children s cholesterol levels and those of their parents. This study focused on gathering fasting total cholesterol as well as LDL levels in American children and adolescents between the ages of 1 and 19 years. They found that the 75 th percentile for these ages in total cholesterol was 170 mg/dl, and the LDL was at 110 mg/dl. The 95 th percentile ranged from 200 mg/dl in total and 130 mg/dl in LDL cholesterol. For American children as a whole, the average total cholesterol is roughly 160 mg/dl, while the LDL is around 100 mg/dl. Upon closer examination of data gathered from the LRC Prevalence Study it was noted that between 5-10% of children and adolescents aged 0-19 years would meet the high classification of total and LDL cholesterol levels according to the panel (Lauer et al, 1992). There was also similar data gathered by the National Health and Nutrition Examination Survey (NHANES) III ( ) which reported around 10% of adolescents between the ages of having total cholesterol values over 200 mg/dl. They also reported an average of total blood cholesterol at 165 mg/dl for children and adolescents between the ages of 4-19 years. This data was also broken down to include race and gender as variables, with black females having the highest cholesterol levels and white males having the lowest values. The average LDL cholesterol for adolescents between years of age was 96 mg/dl, with the same gender and racial trend as highlighted above (Hickman et al, 1998). Yet another study involving lipid measurement was done in Scottsdale, Arizona with 1140 fifth grade students included. This study s data concluded that 14% of children had elevated total cholesterol greater than or equal to 200 mg/dl, and 31% of the total cohort had their total cholesterol between 170 and 200 mg/dl (Bell, and Joseph, 1990). Although the data

18 13 reported by various studies are all different, they all range within a few percentage points from one another. Therefore, each epidemiologic data reported only strengthens that found of other studies, showing that the reference range is indeed accurate of the United States population. The prevalence and epidemiology of elevated lipids in children and adolescents is one of only many factors when looking at the proposed research question. Another important question regards the relevance of the parental cholesterol having to be greater than or equal to 240 mg/dl. The NCEP produced this guideline through research and data collection and its rationalization will be discussed below. The rationale that the NCEP panel had when making the cut point of parental cholesterol levels at 240 mg/dl dealt with the sensitivity for identifying children with elevated LDL cholesterol over 130 mg/dl. Using the LRC data set once again, the panel noted that when the cut point of parental cholesterol was 200 mg/dl or higher 63.5% of children would be screened, which would correctly identify 86.5% of the children aged 0-19 years with elevated LDL. The sensitivity for identifying elevated LDL levels stopped decreasing when the parents total cholesterol value went beyond 240 mg/dl, representing 40.5% of children with elevated LDL. This demonstrated that most likely these children and adolescents had some form of familial high blood cholesterol when compared to children with similar LDL levels but no positive family history (Lauer et al, 1992). The NCEP panel noted that around 5% of United States children and adolescents will have over 130 mg/dl LDL cholesterol, but only about 2% of these will also meet one of the two screening criteria (high parental cholesterol or early cardiac disease). Overall, using the LRC data the NCEP found that 25.1% of all children and adolescents would be tested, with 19.5% being because of high parent cholesterol and 5.6% being because of a positive family history of premature cardiovascular disease (Lauer et al).

19 14 The NCEP has not been the only organization interested in early children and adolescent cholesterol screening throughout the years. The AAP has also issued recommendations in 1998 with overlapping data collected by NCEP. The screening recommendations are the same as issued by the NCEP, with the high levels of LDL defined as being over 130 mg/dl (O Loughlin et al, 2004). There are two approaches to lower cholesterol values in youths, one being the population approach and the other the individualized approach. The population approach is designed to target health professionals, schools, the food industry, etc to help change habits of nutrient intake and eating patterns in all children and adolescents. The individualized approach specifically looks at high risk children and adolescents through selective screening as already described by NCEP criteria (Klish et al, 1998). When looking specifically at the individualized approach, there is a precise algorithm that is used to assess the risk that the child/adolescent has of developing cardiovascular disease. This algorithm was derived originally from the NCEP, but was again adopted by American Academy of Pediatrics. If a child/adolescent is being selectively screened due to their positive family history as outlined previously as the NCEP criteria, a lipoprotein analysis will be ordered with a 12 hour fasting period. Acceptable total cholesterol is below 170 mg/dl and an acceptable LDL is below 110 mg/dl. If the child/adolescent is being selectively screened due to a parent(s) having blood cholesterol greater than or equal to 240 mg/dl than a total blood cholesterol is drawn. When the blood cholesterol results are less than 170 mg/dl than repeat cholesterol is done within 5 years. If the results are between mg/dl than a repeat cholesterol is done immediately and averaged with the previous measurement. If the cholesterol average is greater than 170 mg/dl than a lipoprotein analysis must be done. If the original blood cholesterol reading is greater than or equal to 200 mg/dl a lipoprotein analysis is done with no further

20 15 questioning (Lauer et al, 1992). By viewing this algorithm it becomes apparent that the history taken by the health care provider plays a large role in the care and management of the child or adolescent. A study was done in 2003 to assess the usefulness of the parent history of cardiovascular disease and/or hyperlipidemia as a screening criterion for hyperlipidemia in children and adolescents. The study involved a population based survey with data collected from 3665 eligible Quebec children and adolescents aged 9, 13, and 16 years. Of the eligible children, 2217 subjects had parent questionnaires and blood draws performed. Parent history was assessed with a five question survey regarding hyperlipidemia risk factors, and the blood draw was an overnight fast. Approximately 25.6% of parents reported a history of cardiovascular and/or hyperlipidemia in themselves. The LDL levels collected showed 18.3% of all subjects with a borderline LDL (greater than 2.8 mmol/l) and 4.8% of all subjects with a high LDL level (greater than 3.4 mmol/l). When looking at the data of those subjects with an elevated LDL level, 18.3% were picked up using random screening techniques and 23.7% were detected using family history screening criteria (O Loughlin et al, 2004). Therefore, more subjects were detected using family history screening criteria, which again shows the importance for a thorough history in parents of children and adolescents. Not only do the NCEP and AAP have guidelines issued regarding early cholesterol screening in children and adolescents, but the AHA also has a scientific statement regarding the prevention of cardiovascular disease beginning in childhood. As previously mentioned, there have been many studies that show atherosclerotic changes begin in childhood and extend into adulthood. Other risk factors that will increase chances of atherosclerosis are elevated LDL cholesterol, elevated triglycerides, elevated systolic and diastolic blood pressures, elevated body

21 16 mass index (BMI) and cigarette smoking (Kavey et al, 2003). Therefore the AHA has focused on not only cholesterol levels, but other important risk factors as well. For example, they recommend assessing diet at every patient visit with limitations on highly saturated foods and excessive salt intake. Smoking initiation should be monitored and avoidance of second hand smoke mentioned. The activity of the child should be assessed with emphasis on reducing time spent watching television, playing video games, etc. Special attention should also be given to family history, blood pressure measurements, and body habitus (height, weight, and BMI calculations) (Kavey et al). Another AHA statement was released in 2002 specifically for health professionals regarding atherosclerosis, hypertension, and obesity in children and adolescents. This statement focuses on many secondary risk factors that may lead to elevated lipid levels. For example, they focus on physical activity, obesity, insulin resistant and type two diabetes, high blood pressure, high blood cholesterol, and cigarette smoking present in the pediatric population (Williams et al, 2002). These clinical indicators alone may target a child for early cholesterol screening regardless of family history and parent blood cholesterol levels. The specific strategies discussed in this AHA statement are again the recommendations by the NCEP, which include the population strategy and individual strategy. Initial dietary intervention is the mainstay of treatment, with low intake of saturated fat and cholesterol. If three months of maintaining a strict diet still do not lower LDL levels below 130 mg/dl a more aggressive diet is initiated (Williams et al). Further discussion regarding specific dietary modifications and pharmacologic treatment will be found at the conclusion of the literature review. Now that a sufficient background has been given regarding the screening indicators and their implications, it is important to look at studies that have tested the applications of these

22 17 criteria. The first study discussed focused on examining the prevalence of screening indicators and evaluating the relevance of the indicators in detecting high levels of LDL. Subjects consisted of those from the Cincinnati Myocardial Infarction and Hormone (CIMIH) Family Study, which was an epidemiologic study conducted in 1988 and 1989 (Diller, Huster, Leach, Laskarzewski, and Sprecher, 1995). A total of 232 children and adolescents between two and nineteen years of age were included in the study. Using the NCEP criteria, 47.8% met major screening indicators, being family history of premature cardiovascular disease or parent blood cholesterol greater than or equal to 240 mg/dl. Using secondary or discretionary indicators (high fat diet, hypertension, obesity, smoker, steroid medication, or diabetes) 54.7% of children met screening criteria. 28% of the subjects had both a major and discretionary screening indicator. This same cohort had LDL lipid levels drawn, which resulted in 25% of cohort having elevated LDL levels (greater than or equal to 110 mg/dl). The data analysis showed that the more screening indicators present the higher the levels of LDL cholesterol (Diller, Huster, Leach, Laskarzewski, and Sprecher). When looking at each indicator, 27% had only a discretionary indicator and 19.8% had only a major screening indicator with an overlap of 27%. The NCEP panel had suggested that parent cholesterol alone would initiate screening in 20% to 25% of population and correctly identify elevated LDL levels in 40% of children. The CIMIH population showed parent cholesterol initiating screening in 29.3% of population, correlating to 61% of children with elevated LDL levels. Overall, the study reported that the major and discretionary indicators were independent of another. In other words a health care provider can not assume that if a major indicator is not present that the child does not have an elevated LDL level. Health care providers can also be confident that if no indicators are present the child or adolescent is at a risk of less

23 18 than 2% of having a high LDL concentration (Diller, Huster, Leach, Laskarzewski, and Sprecher, 1995). Another study was done through the pediatric resource center in Brooklyn, New York in 1989 through This study focused on disadvantaged inner-city children and looked at the family history of coronary heart disease as the main screening tool for identifying children with elevated serum cholesterol (Wadowski, Karp, Murray-Bachmann, and Senft, 1993). There were a total of 300 children included in the study ranging from 2 to 14 years of age. Overall there were 29.3% of these 300 children who had a positive risk for coronary heart disease based on positive family history and 70.7% had a negative family history. The mean total cholesterol for the positive risk group was 4.48 mmol/l and for the negative risk group was only 4.18 mmol/l which were found to be statistically significant with p<.02. The use of family history alone as a screening indicator had a sensitivity of 39.3%, a specificity of 74.5%, and a positive predictive value of 39.8% (Wadowski, Karp, Murray-Bachmann, and Senft). All of this data supports the NCEP premise that early cardiac events in the family of the child and/or adolescent is indeed a very vital component to identifying youth with elevated lipid levels. A study done in 1989 and 1991 looked at students (grades 1-6) and parents from various elementary schools in Michigan and California. This research focused on the value of parents self reported cholesterol levels in identifying children with hyperlipidemia. There were a total of 574 surveys filled out by eligible parents to assess whether their reported cholesterol values corrected targeted high risk children and adolescents. The data analysis showed that if using the NCEP guideline of parent total cholesterol greater than or equal to 240 mg/dl, between 90-93% of children with elevated total cholesterol values (greater than or equal to 170 mg/dl) would have been missed (Resnicow, and Cross, 1993). Although this data seems counterintuitive to the

24 19 basis of this research project, its addition only fine tunes the technicality of the NCEP guidelines. This data supports the importance of knowing more than the self reported parental cholesterol. To adequately determine a child s risk status the parental blood cholesterol must be an actual blood measurement. This will not only benefit the children who will newly fall under the screening guidelines, but also the parents who may not be receiving efficient cholesterol screening in their own health care. Not only have there been numerous studies looking at how specific the NCEP guidelines are at picking up children with elevated cholesterol, there has also been studies reviewing how well health care providers are following the set guidelines. One of the most notable studies regarding this issue looked specifically at cholesterol screening trends in pediatricians (PD), family practitioners (FP), and general practitioners (GP). This telephone survey was a randomized study done in two different time periods, one in 1988 and one in There was a total of 1441 primary care physicians participating in the survey of 1988 and 1036 physicians in the most recent survey of 1995 (Kimm, Payne, Stylianou, Waclawiw, and Lichtenstein, 1998). The data from 1995 was compared to that of 1988 since the NCEP guidelines regarding cholesterol screening in children and adolescents came out in The results from 1995 showed that PD leaded the screening efforts in high risk children and adolescents. The lowest rate of screening was seen in the GP group with a total of 62.5% screening routinely and/or for high risk individuals. The overall population of all physicians gave a total of 75.7% performing routine screening or screening for high-risk children and/or adolescents. Around one third of all GP and FP physicians combined did not screen cholesterol in children at all. The average earliest age for cholesterol screening in children with positive

25 20 family history was 4.7 years for PD and 8.7 years for GP physicians (Kimm, Payne, Stylianou, Waclawiw, and Lichtenstein, 1998). When looking specifically at the treatment for elevated cholesterol levels, 70.8% of all physicians recommended diet as the first line therapy. The most common diet therapy recommended was low-fat diet, with one third also going as far as discussing a low-saturated-fat diet. Around 17.4% of physicians recommended exercise and diet combined. Among all the different physicians, the PD group initiated diet therapy in younger children (average 4.7) with the FP and GP initiating at later ages (around 8). There was also a 16% rate of using drug therapy to treat high cholesterol levels in children. More GP physicians (22.1%) used medications compared to PD (12.1%) and FP (16.1%). The most commonly used drug regimens were cholesterol synthesis inhibitors (48.2%) and bile acid sequestrants (37.8%) (Kimm, Payne, Stylianou, Waclawiw, and Lichtenstein, 1998). Bile acid sequestrants were more commonly used in the PD group and in physicians with less than 15 years of experience, most likely because they were more aware of the new NCEP guidelines issued in When comparing the trends of the survey of 1998 and 1995 there was some surprising results. Overall, there was more routine screening for high cholesterol in children (17% in 1995 versus 9% in 1988) but less screening in children with a positive family history of early cardiac disease (75.3% in 1995 versus 82.7% in 1988). The greatest reduction in screening was by the GP group, and the least reduction in screening by the PD group. When looking at treatment trends, 63% of physicians in 1995 prescribed a low-fat diet, with only 44% doing so in There was an increase of 30% more physicians prescribing some form of exercise as part of the regimen to lower cholesterol levels in the children. The rate of drug therapy has also increased

26 21 with 15.8% using medications in 1995 and only 12% using them in 1988 (Kimm, Payne, Stylianou, Waclawiw, & Lichtenstein, 1998). Another similar study was done on a smaller level in 1990 and only looked at practices of pediatricians from the Minneapolis-St. Paul area. A total of 187 pediatricians were included in the telephone survey which focused on attitudes and practices about pediatric cholesterol screening and subsequent treatment options. The results showed that 90% of all pediatricians screened blood cholesterol, with 33% doing routine screening and 58% doing screening in children with a positive family history of early cardiac events. The majority of the pediatricians (82%) prefer to screen cholesterol when the child is between the ages of 2 and 5 years. When looking at the pediatricians attitudes towards cholesterol screening, 66% feel cholesterol screening should be done in all children and 44% believe only high risk children should be targeted. Although the response rate was great at 90% of pediatricians screening cholesterol, 57% of the same group though they should be doing more screening (Arneson, Leupker, Pirie, and Sinaiko, 1992). Overall, primary care physicians are doing a decent job in screening cholesterol in children and adolescents. However, it is apparent that the NCEP guidelines of 1991 have not made much of an impact on their screening methods. In fact, cholesterol screening in high risk children and adolescents was actually shown to have decreased from 1988 (Kimm, Payne, Stylianou, Waclawiw, and Lichtenstein, 1992). All of this data has just proved the importance of the knowledge of current guidelines and how they must be implemented into everyday practice. The last aspect reviewed in the literature was regarding therapies recommended in children and adolescents who were found to have elevated lipid levels. Dietary instruction is warranted for all children and adolescents with a total cholesterol level greater than or equal to

27 mg/dl or an LDL greater than or equal to 110 mg/dl. Within this subset, those children with borderline levels of total cholesterol ( mg/dl) and LDL cholesterol ( mg/dl) are all counseled on the Step-One Diet. Specifically the Step-One Diet calls for an average intake of saturated fatty acids making up less than 10 percent of the total daily calories. It also recommends that total fat calories make up no more than 30 percent of total daily calories, and that less than 300 milligrams of cholesterol is consumed each day (Lauer et al, 1992). Those children that reach the LDL cholesterol goal of less than 110 mg/dl are followed up in one year for reevaluation. When the Step-One Diet is tried for at least 3 months with no benefit, the child usually progresses to the Step-Two Diet. Those children who have failed to improve their LDL cholesterol and those that initially start with high levels of total cholesterol (greater than or equal to 200 mg/dl) or LDL cholesterol (greater than or equal to 130 mg/dl) are started on the Step-Two Diet. This has all the same criteria as the Step-One Diet except the saturated fatty acids are to make up less than 7% of total calories and the total cholesterol should be less than 200 milligrams per day. At this stage it is very important to involve a dietitian to make sure the child is still receiving enough vitamins, minerals, and other nutrients in their diet. These subsets of children who have LDL cholesterol greater than or equal to 130 mg/dl also need further evaluation for secondary causes of hypercholesterolemia. It is also important to screen other family members to rule out the two most common familial disorders, familial hypercholesterolemia and familial combined hyperlipidemia (Lauer et al, 1992). It is very important to diagnosis these conditions since most children have to be started on pharmacologic treatment with familial disorders. Pharmacologic therapy is considered in children ages 10 years and older that have tried diet therapy for 6 months to one year without significant benefit. If the LDL cholesterol remains

28 23 greater than or equal to 190 mg/dl or if the LDL cholesterol is greater than or equal to 160 mg/dl and there is a positive family history of premature cardiovascular disease or there are two or more other cardiac risk factors in the child or adolescent s medical history (obesity, smoking, hypertension, diabetes). The goal LDL cholesterol is less than 130 mg/dl with a follow up appointment 6 weeks after starting a medication and every 3 months to monitor progress on lipid levels. The drugs of choice for children and adolescents are the bile acid sequestrants cholestyramine and colestipol. The most common side effects of these medications are nausea, constipation, bloating, and flatulence, therefore it is important to start each child on the lowest dose possible (Lauer et al, 1992). All of the above aspects in the review of literature could have been expanded on more than what they already were. There are hundreds of articles on cardiovascular health issues, considering cardiovascular heart disease is still a top killer of people worldwide. Although a lot has been touched on while reviewing the literature, this topic is ever changing and growing each day. The literature review was done using Medline and CINAHL for databases located on OhioLink. Hypercholesterolemia was used as a keyword and also expanded using prevention, control, and treatment of elevated cholesterol. PubMed was also used as a research engine, looking up general information about the biochemistry of cholesterol as a molecule. In conclusion to the literature review, the research question posed as the foundation of this project was: Are health care providers screening cholesterol at an early enough age in children and adolescents, especially those with heath and family risk factors? The proposed hypothesis was that although health care providers may be aware of the NCEP guidelines and the importance of early detection of elevated cholesterol levels, they are not screening with the protocols set forth by the national guidelines.

29 24 Chapter III - Methodology Upon completion of the literature review in the spring of 2005, a data collection tool was created to organize the data within the charts reviewed. This tool was designed using NCEP criteria for cholesterol screening in children and adolescents as well as including general epidemiologic features. Researcher, Dr. Sandra Puczynski, gave helpful suggestions to create the final draft of this data collection tool. Once this was complete the entire project went through Institutional Review Board (IRB) application and review at the Medical College of Ohio at Toledo (MUOT). Final IRB approval was granted in June of After contact with the MUOT Family Practice Center (FPC), specific dates were assigned to conduct this retrospective chart review. At the FPC, Dr. Mark Wiener, a family practice attending physician assisted with identifying eligible patients. The FPC used family charts which combine all family members medical records into a single family chart. The chart review focused on parents of children and adolescents that were known to have high cholesterol, or that met other screening criteria according to the NCEP. First, children aged 2-19 years who are seen in practice were identified, whose parents were also followed in the practice. Dr. Weiner s office assistant Mary Raskel helped compile a list of all children seen at that office that had one or both parents also seen in the office. Another inclusion criterion to this chart review was that the children and adolescents were seen at the practice between January 1, 2000 and May 31, Once these families were identified, it was determined whether or not one or both parents had a diagnosis that met the NCEP criteria or ICD.9 code, which places their offspring at increased risk for atherosclerosis and hypercholesterolemia. These criteria were having one or both parents with elevated total cholesterol equal to or greater than 240 mg/dl. The other criteria include early cardiac events