Nancy Conroy, MD

Morris Schoeneman, MD

Department of Pediatrics

SUNY-Downstate Medical Center

Brooklyn, NY

Pretest

Q1: True or False?

Primary hypertension is the most common cause of elevated blood pressure in older children and adolescents.

Q2: Best Answer; sodium handling by the kidney in African Americans compared to non-Hispanic whites is:

a) more efficient

b) the same

c) less efficient

Q3: True or False. Low Na+ diet alone is as effective in treating hypertension as a low Na+ diet plus K+, Mg++ and Ca++ supplements.

Q4: Best answer; which of the following is an important contributing factor toward elevated blood pressure as an adult?

a) low birth weight

b) small birth weight to placental size ratio

c) excessive weight gain in the first year of life

d) poor weight gain after the first year of life

e) all of the above contribute

Q5: Best answer; after starting a low Na+ diet a decrease in blood pressure can be seen as soon as:

a) 3 days

b) 1 week

c) 2 weeks

d) 1 month

Objectives

On completion of this module, the Residents will be able to:

1. Define the parameters of hypertension in the pediatric population

2. Appreciate the correlation between blood pressure and weight, height and gender

3. use non-pharmacologic approach to treatment of hypertension in children and adolescents

Facilitator preparation

The facilitator should review the physiology of blood pressure control in any of the standard Pediatric text books (Nelson, Rudolph, Oski) as well as:

1. The DASH eating plan from the National Heart, Lung and Blood Institute, National Institute of Health, May 2003. This can be found at www.nhlbi.nih.gov/health/public/heart/hbp/dash/

2. Barker DJ, Eriksson JG, Forsen T, Osmond C. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol. 2002 Dec;31(6):1235-9. Papers addressing the Barker hypothesis and hypertension appear regularly. The editor's favorite is

3. Krishnaswamy K, Naidu AN, Prasad, Reddy GA. Fetal malnutrition and adult chronic disease. Nutrition Reviews; 60(5): 35s.

4 National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. Update on the 1987 task force report on high blood pressure in children and adolescents: a working group report from the National High Blood Pressure Education Program. Pediatrics 1996; 98:649-58.

Abstract

Primary hypertension in children and adolescents is becoming more prevalent as children become more obese and lead sedentary lives. However, the pathophysiology involved begins for the individual in-utero and is influenced by the mother's diet and infant birth weight. The diagnosis of primary hypertension is never made in children without a thorough evaluation to rule out the existence of a correctable underlying disease entity. After this diagnosis is made dietary therapy is initiated with the understanding that pharmacotherapy may also be required later on if no substantial improvement is observed.

Systemic hypertension in infants and children is uncommon and when present may be secondary hypertension due to an underlying disease entity, typically of the renal system. Often in these cases treatment and management of the initial disorder correct the hypertension. Primary hypertension is more common in older children and adolescents, although not restricted to this age group, and has a reported prevalence of 1% or less. (Kay et al, 2001) 2 It is important to detect and treat primary hypertension in this population because studies show a significant association between the presence of elevated blood pressure in children and adults with hypertension.

Essential hypertension is never assumed in childhood. All Children Must Receive A Work-Up

A number of studies have shown that children with a blood pressure above the 90th percentile have over 2-3 times the risk of having hypertension as adults, and 45% of adults with hypertension were found to have had blood pressures over the 90th percentile as children. Perhaps these represent adults whose cause for elevated blood pressure was missed

The range of normal blood pressures in the pediatric population depends on several factors including the patient's age, height, and sex. The most recent guidelines published by the National High Blood Pressure Education Program in 1996 state that hypertension in children is defined as a blood pressure above the 95th percentile for the patient's particular categories. High normal is considered to be between the 90th and 95th percentiles, and a normal blood pressure in children and adolescents is below the 90th percentile. Any child presenting with a blood pressure at or above the 95th percentile should undergo a complete evaluation to attempt to determine the cause of hypertension.

A Case Study - Part 1

Michael is a 12y.o. Haitian boy that you are seeing for the first time for a well-child visit. Michael was born in Haiti and moved to the United States with his mother and siblings at the age of five. The mother reports his birth weight as 2.3 kg. (5.06 lbs.). He had diarrhea during the first year of life and gained slowly to 8.0 kg. (17.6 lbs.) at one year. After that, she reports "He ate really well."

Michael has no chronic medical conditions and has never had to be on medication for anything. His mother, age 35, is a single parent who works full time in a grocery store and was diagnosed several years ago with hypertension and non-insulin dependent diabetes mellitus. Her employer does not provide medical insurance benefits. His father is not with the family but the mother is able to inform you that he is 42 years old and has hypertension. Michael has three siblings by a different father, two younger sisters, ages 11 and 9, and a younger brother, age 4; they are all healthy.

Michael is currently in the sixth grade at a local public school and has a B average. He buys both breakfast and lunch at school. Most days after school he and his sisters go to a neighbor's house where they will usually eat some type of snack and occasionally dinner. Michael's mother reports that he has a good appetite and eats meat, cereals and grains, but refuses to eat vegetables. He will occasionally drink orange juice in the morning but usually has soda with his meals.

On physical exam you find that Michael is 58inches tall (50%ile) and weighs 130lbs. (95%ile) with a BMI of 27 kg/m2. [Take weight divided by height squared in pounds and inches and multiply by 703 to get BMI in kg/m2) His vital signs are within normal limits except for a BP of 128/82.

Q1. What risk factors does Michael have for hypertension?

A1. Michael is an African American. Major differences that have been recognized between black and white hypertensives are primarily epidemiologic, with hypertension being more prevalent, having an earlier onset, and having more severe sequelae in the black population. Data show that a difference in sodium handling may contribute to the particular hemodynamic and hormonal profile of black hypertensives. (Saunder, 1991) Michael was also a low birth weight infant who gained poorly in the first year of life. As shown by David Barker and others in over twenty studies, children who are born small for dates, after reduced fetal growth (a different category than pre-term infants) and proceed to gain poorly in the first year of life followed by rapid compensatory growth are found to have elevated blood pressure as adults. (see references by Barker as well as modules on hypercholesterolemia and Type 2 DM) African-Americans in the U.S. have a 3-fold higher prevalence of low birth weight compared to Caucasians and non-Hispanic whites. (National survey, 1996)

According to Barker "persisting raised blood pressure seems to be associated with interference with growth at any stage of gestation, since it is found in people who were thin or short babies or proportionately small." (Barker references) There are several possible mechanisms including how the fetus is affected by small variations in the balance of macro-nutrients in the maternal diet during gestation rather than by relatively large variations in the absolute amounts and the ratio between birth weight and placental size. (see Krishnaswamy, 2002)

These associations are less consistent in adolescence, presumably because the tracking of blood pressure from childhood through adult life is disrupted by the adolescent growth spurt. (National Survey) Finally, these relationships were not confounded by socio-economic conditions at the time of birth or in adult life.

Another theory suggests a relationship with low birth weight and a concomitant deficit in total nephron number, representing a "first hit" in susceptible individuals to the development of hypertension and kidney disease in later life. (luycks, et al) Animal studies have revealed an association between low birth weight and adult hypertension that appears to be a result of congenital nephron deficit occurring with intrauterine growth retardation. This lack of nephrons consequently results in a decreased filtration surface area and limitation of renal sodium excretion.

An important component observed between low birth weight infants and hypertension later in life is the maternal diet during pregnancy. Mothers with a higher intake of carbohydrates during pregnancy and a limited amount of protein (<50g daily) were found to have children with higher blood pressures. (Barker et al, 1998) Twin studies have provided additional corroborating data showing that intrauterine factors resulting in low birth weight have an independent effect on blood pressure.

Q2. Is Michael more likely to have secondary or primary hypertension?

Here's a chance to open the discussion to residents. Ask, Are we permitted to make a diagnosis of primary hypertension in a child?" The answer is an absolute, "No." Ask, "Why not?"

A2. A diagnosis of "primary hypertension" in a child cannot be made without a comprehensive workup to exclude treatable causes. It is necessary to have three elevated measures, one month apart, to make the diagnoses of hypertension.

Ask residents to list causes for a false diagnosis of hypertension

A complete pre-evaluation of chronic hypertension includes:

Table 1. Categories of hypertension to be "Ruled out:"

1. "factitious" causes of hypertension (improper cuff size-proper cuff width is two thirds of upper arm length-or measurement technique [i.e., manual versus Dynamap])

2. "nonpathologic" causes of hypertension (fever, pain, anxiety, muscle spasm)

3. iatrogenic mechanisms (medications and excessive fluid administration)

4. "white coat syndrome"

Teaching comment: A proper evaluation of hypertension is both expensive and wearing. Br sure that the child is actually hypertensive!

The complete evaluation for truly hypertensive children includes

History and physical examination: Headache, blurred vision, history of UTIs, family history of renal dysfunction/hypertension, pitting edema, dyspnea on exertion, jugular venous distention; or displaced point of maximal impulse (PMI), absent femoral pulses, abdominal masses or bruits, thyroid enlargement.
Laboratory studies: Urinalysis with microscopic evaluation, urine culture, serum electrolytes, CBC, creatinine, BUN, calcium, uric acid, cholesterol, and plasma renin level.
Imaging: Renal ultrasonography, including renal artery Doppler and other imaging studies as indicated (echocardiography, renal arteriography, nuclear renal scanning, and magnetic resonance imaging).
Consider toxicology screen, HCG (human chorionic gonadotropin), thyroid function tests, urine catecholamines, plasma and urinary steroids.

The comprehensive evaluation is generally performed by a pediatric nephrologist; however, a generalist is quite capable of working closely using internet and similar resources to complete the evaluation.

Q3. According to the blood pressure tables given (see Appendix A), does Michael have hypertension? If yes, is it severe or mild and what should be done after this one measure?

Ask resident the principles of assessment. They should know that there is a height %ile cross actual measurement criteria.

Michael's systolic BP of 128 on this first visit is substantially elevated. It has not, however, been replicated at subsequent visits, nor has there been an evaluation looking for common causes of secondary hypertension. With such a high level and the increased risk, therapy and evaluation could begin in tandem. Michael needs guidance on simple steps to lose weight including diet and exercise. This initial measurement of an elevated blood pressure requires two more measures, one month apart, of increased BP to make a formal diagnosis of hypertension.

The Case study continues - part 2

Michael is diagnosed as having primary hypertension. He and his mother are educated on and strongly encouraged to start the DASH diet. The most difficult aspect of the diet to them will be the addition of fruits and vegetables because Michael says he does not like them and often refuses to eat any. The family's normal eating habits are evaluated and changes and additions are suggested based on their ethnic food habits.

Q4. Is it appropriate to use medications for Michael in the initial phases of treatment or should diet and exercise management be emphasized?

Always begin with diet and exercise - non-pharmacologic therapy. There is disagreement among Pediatricians as to whether or not hypertension in children and adolescents should be treated pharmacologically. There are several reasons for this dispute. The first of which is that the use of antihypertensive medications in children has not been shown to decrease the risk of stroke or coronary artery disease as adults. (Kay, et al, 2005) Next, starting antihypertensive therapy during childhood exposes them to a much longer period of medication than if that treatment were begun in adulthood, and also during a particularly susceptible period of much growth and development.2 Finally, no formal studies have looked at the safety and efficacy of these medications in the pediatric population. Much of what is known has been derived from uncontrolled use in children and extrapolation of the effects of these drugs in adults.

Q5. How would you initiate management of Michael's hypertension? Should he be started on antihypertensive medication?

Pharmacologic treatment for hypertension in children and adolescents is reserved for those with blood pressure levels above the 95th percentile who are symptomatic and/or have demonstrable end-organ damage and/or do not respond appropriately to non-pharmacologic treatment.2 Michael's initial systolic blood pressure of 128 places him significantly above the 95th percentile for his height. Since he is asymptomatic, and assuming that no end-organ damage has yet occurred, he need not necessarily be started on antihypertensive medication. However, if pharmacologic treatment were warranted for this patient, no particular class of antihypertensive drugs has been shown to be superior to another class in terms of effectiveness in children, therefore virtually any pharmacotherapy could be initiated.2

Considering these guidelines, a nonpharmacologic approach to treatment of hypertension in children and adolescents is the best initial management. Pharmacologic therapy begins if diet and exercise are insufficient, but non-pharmacologic - lifestyle changes - therapy should continue in tandem with drug therapy.

Q6. What measures for diet therapy are currently recommended?

Many studies have looked at the relationship between individual dietary components and blood pressure. The most popular ones have investigated the effects of varying sodium levels. Other investigations have looked at the relation of potassium, magnesium or calcium to blood pressure. The biggest criticism of these studies is the fact that they attempt to analyze the correlation between these minerals and blood pressure in isolation from the diet as a whole.

Each of these respective studies has concluded that adequate amounts of these individual nutrients when supplemented to a regular diet help to reduce blood pressure. However, most of them also agree that the required amounts to produce an effect are no more than the recommended daily allowance already advised. Wouldn't it be better then to look at the American diet as a whole to see how all nutrients when combined in varying degrees by consumption from natural food sources effect blood pressure?

In 1997 the New England Journal of Medicine published the results of a research study sponsored by the National Heart, Lung and Blood Institute that looked at exactly this. A four-arm protocol was initiated for adults with systolic blood pressures between 140 and 16 mmHg. The sample was weighted with African-American men as this is the most severely affected group.

Group 1 No change,

Group 2 Emphasize low sodium/high potassium foods (4 or 5 servings of fruits, and vegetables and whole grains each day ;

Group 3. Emphasize calcium containing foods (2 or 3 servings of low or no-fat dairy products); and

Group 4, Emphasize both dietary regimens

Ask residents to predict the results of non-pharmacologic therapy. The data show a drop in systolic blood pressure of 8 or mmHg for patients using either the fruit/vegetable intervention or the high calcium intervention. The drop increased to 16 mmHg for patients using both interventions. [The mmHg cited was for African American men. Similar though less striking findings were shown for all other groupings.)

The article, entitled "A clinical trial of the effects of dietary patterns on blood pressure", asserted that a diet rich in whole grains, fruits, vegetables, and low-fat dairy products can substantially lower blood pressure. This diet has come to be known as the DASH diet (Dietary Approach to Stop Hypertension). A complete DASH diet (#4, above) lowered systolic BP 16 mmHg in African American men with essential hypertension. The general scheme of the DASH diet is shown below, followed by a sample menu.

Sample menu for the Dietary Approaches to Stop Hypertension (DASH) diet:

Here is a sample menu for the Dietary Approaches to Stop Hypertension (DASH) diet. It is based on a 2,000-calorie diet.

Breakfast

1 cup corn flakes with 1 teaspoon of sugar
8 ounces low-fat milk
1 banana
1 slice whole-wheat toast
1 tablespoon jelly
½ grapefruit

Lunch

2 ounces sliced turkey
1 pita bread
1 tablespoon low-fat mayonnaise
Raw vegetables: 3-4 carrot sticks, celery sticks, radishes, 2 loose lettuce leaves
½ cup fruit cocktail

Snack

¼ cup dried apricots
¾ cup mini pretzels
1/3 cup mixed nuts
1 cup flavored low-fat yogurt

Dinner

3 ounces grilled lean beef
1 cup scallion rice
1 cup steamed broccoli
Spinach salad with ½ cup raw spinach, 2 cherry tomatoes, 2 cucumber slices
1 tablespoon light Italian dressing
8 ounces low-fat chocolate milk

Questions…

Q7. How would you approach a discussion to dietary changes in this family?

It is important to review the family's current diet and attempt to make changes and/or additions that are consistent with their cultural/native eating habits.

Case study - conclusion

Michael is now 16 years old. After you first saw him and made the diagnosis of primary hypertension his mother made an effort to educate herself and her children on the healthy eating habits recommended by the DASH diet plan. In addition to planning out dinners, Michael and his mother and siblings would make bag lunches to bring to school rather than purchasing lunch in the cafeteria. Michael's mother also strongly encouraged her son to become more physically active and two years ago Michael joined the school basketball team. Michael's weight has decreased to between the 50-75%ile and his BMI is now 24. He is also a much happier child since he has become more active and is no longer a target of teasing from his peers due to his weight. His blood pressure is well controlled by diet and exercise and today is found to be 116/75, well below the 90%ile for his age and height.

References

Barker DJ. Fetal origins of coronary heart disease. BMJ 1995 July 15; 311: 171-74.

Barker DJ. In utero programming of chronic disease. Clinical Science. 1998; 95: 115-28.

Barker DJ. Fetal origins of cardiovascular disease. Ann Med. 1999 Apr; 31 Suppl 1:3-6. Review.

Barker DJ, Eriksson JG, Forsen T, Osmond C. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol. 2002 Dec;31(6):1235-9.

DASH eating plan, National Heart, Lung and Blood Institute, National Institute of Health, U.S. Department of Health and Human Services, May 2003. [www.nhlbi.nih.gov/health/public/heart/hbp/dash/]

Eriksson JG, Forsen T, Tuomilehto J, Winter PD, Osmond C, Barker DJ. Catch-up growth in childhood and death from coronary heart disease: longitudinal study. BMJ. 1999 Feb 13;318(7181):427-31.

Kay JD, Sinaiko AR, Daniels SR. Pediatric hypertension, American Heart Journal, (Results of Expert Meetings: Conducting Pediatric Cardiovascular Trials), Vol. 142, No. 3, September 2001, Copyright © 2001 Mosby, Inc.

Krishnaswamy K, Naidu AN, Prasad, Reddy GA. Fetal malnutrition and adult chronic disease. Nutrition Reviews; 60(5): 35s.

Luyckx VA, Brenner BM. Low nephron number: Initial "hit" in adult hypertension and renal disease. Nephrology Rounds. 2004 Feb; 2(2): 1-6.

National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. Update on the 1987 task force report on high blood pressure in children and adolescents: a working group report from the National High Blood Pressure Education Program. Pediatrics 1996; 98:649-58.

Osmond C, Barker DJ. Fetal, infant, and childhood growth are predictors of coronary heart disease, diabetes, and hypertension in adult men and women. Environ Health Perspect. 2000 Jun;108 Suppl 3:545-53. Review.

Roseboom TJ, van der Meulen JHP, van Montfrans GA, Ravelli AC, Osmond

C, Barker DJ, Bleker OP. Maternal nutrition during gestation and blood

pressure in later life. Journal of Hypertension. 2001 Jan; 19(1): 29-34.

Saunder E. Hypertension in blacks. Primary Care. 1991 Sep; 18(3): 607-

Annotated Answers

A1. The Answer is True. There is a correlation between age and primary hypertension. One must never assume that a young child has primary hypertension

A2. The Answer is c. In general, African Americans have a sodium or salt dependent hypertension reflecting a lessened ability to handle sodium ion.

A3. The Answer is False. A remarkable finding of the Dietary Approach to Stop Hypertension (DASH) studies is that combined therapy with a diet low in sodium and high in Calcium, Potassium, and dietary fiber is more effective than a diet focusing on only one of these elements.

A4. The Answer is e. All of these observations have been supported by epidemiological data. Answers a, b, and d are part of a "programming theory" proposed by David Barker. Answer c is supported by data provided by Alan Lucas and a theory of fat cell growth promoted by Knittle and Hirsch about 40 years ago.

A5. The answer is b. It takes about one week for the dietary changes in DASH to show effect.