Heredity and hypertension: metabolic characteristics

Impact on

This study was performed to evaluate the possible role of heredity in the clinical characteristics of hypertension. Metabolic, endocrine, and renal measurements were compared in subjects with normal blood pressure who had a family history of hypertension (n = 60) with those of subjects with normal blood pressure who did not have a family history of hypertension (n = 48). The groups were matched for age (mean, 44 k 2 years and 45 f 2 years) and blood pressure (127 f l/77 + 1 mm Hg and 127 f 2/77 + 1 mm Hg). The following parameters were higher in the patients with a family history of hypertension than in those without. Plasma insulin concentrations (14.1 f 1.1 vs 10.8 +- 1.0 clU/ml; p < 0.05), insulin-glucose ratio (0.15 + 0.01 vs 0.11 i 0.010; p < 0.05), norepinephrine concentrations (315 * 24 pglml vs 208 -+ 20 pglml; p < O.Ol), plasma renin activity (2.1 ~fr0.2 ng AngllmVhr vs 1.6 + 0.2 ng Angl/ml/hr; p < 0.02), total cholesterol levels (217 i 8 mgldl vs 197 f 0.3 mg/dl; p < 0.05), creatinine clearance (125 + 9 ml/min vs 96 -t 8 mllmin; p < O.Ol), and albumin excretion rate (3.2 f 0.3 pglmin vs 2.6 + 0.3 pglmin; p = 0.1). Moreover, patients with a family history of hypertension had smaller increases in systolic blood pressure during treadmill exercise (55 f 3 mm Hg vs 64 f 3 mm Hg; p < 0.03). There were no differences in echocardiographic left ventricular mass index between the groups. These findings suggest that a family history of hypertension predicts small but significant changes in neuroendocrine, metabolic, and renal values in adults with normal blood pressure. Since age makes future essential hypertension unlikely in these patients, the differences in these measurements may reflect inherited clinical associations of hypertension that are independent of blood pressure. (AM HEART J 1992;124:435.)

Joel M. Neutel, MD, David H. G. Smith, MD, William F. Graettinger, MD, Robert I,. Winer, MD, and Michael A. Weber, MD Long Beach and Irvine, Calif,

Children of persons with hypertension are predisposed to the development of hypertensioql and this hereditary tendency probably involves a polygenetic system.2 However, the pathogenesis of hypertension and the mechanisms that mediate its clinical characteristics are not well understood. It is clear that clinical hypertension comprises more than just high blood pressure3; previous studies have shown that indices of insulin and lipid metabolism,4 renal function,” and left ventricular structure and function6 can be altered very early in the course of hypertension. Indeed, these findings have raised the possibility that measurable metabolic and cardiovascular changes may precede increases in blood pressure. In contrast to earlier studies that have focused on metabolic features of children or young adults,6-g this report

From t.he Hypertension Center, Veterans Affairs Medical Center, Long Beach, and the University of California, Irvine. Received for publication Jan. 6, 1992; accepted Feb. 20, 1992. Reprint requests:Michael A. Weber, MD, Hypertension Center (W130), VA Medical Center, 5901 East Seventh St., Long Beach, CA 90822. 411138089

describes findings in middle-aged adults with normal blood pressure and a family history of hypertension. Specifically, to determine whether the clinical characteristics of the hypertension syndrome might be inherited, we have compared metabolic, renal, and endocrine measurements in subjects with normal blood pressure and a family history of hypertension with those of normal volunteers without a family history of hypertension. METHODS

One hundred and eight volunteers, aged 20 to 73 years (meanage,44years), participated in this study. There were 86 men and 22 women;88 subjectswerewhite, 9 wereblack, and 11 were Hispanic. The meanweight of the participants was 83.2 i 1.4 kg, mean height was 175.0 f 1.0 cm, and mean body massindex was 27.2 + 0.4 m2. Normal blood pressurewas verified in each subject by a mean daytime blood pressure(meanof all diastolic pressuresasmeasured by ambulatory blood pressuremonitoring between6:00AM and 10:00 PM) of less than 85 mm Hg. The group was divided into two subgroupson the basisof presenceof a first-degree family history (father, mother, or sibling) of hypertension (n = 60; 45 men, 15women;48 white, 5 black, and 7 Hispanic subjects) or absenceof a family history of 435

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August 1992 Heart Journal

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Fig. 1. Plasma immunoreactive insulin concentrations and the insulin-glucose without a family history of hypertension. Plotted values are means t SEM.

Table

I. Clinical

(Mean

characteristics

5 SEM)

Age (yr) Height (cm) Weight (kg) BMI (kg/m?) Systolic BP (mm Hg) Diastolic BP (mm Hg)

Family histor) of hypertension (n = 60) 44.2 174.4 83.5 27.4 127

k * f i

1.6 1.4 1.8 0.5

i 1 77 t 1

No family histog r)f hypertension in = 48) 44.8 175.3 83.0 26.8 127 77

+ i i -t i i

1.8 1.4 2.2 0.6 2 1

BMI. Body mass index: BP. blood pressure (mean Xhrwri

NEGATNE

ratio in subjects with and

Table II. Blood values in patients ily history of hypertension Parameter

Total cholesterol (mg/dl) Triglycerides (mg/dl) HDL cholesterol (mg/dl) Plasma renin activity (ng Angl/ml/hr) Aldosterone (pg/ml) Glucose (mgidl)

with and without

Fumi1.v hi&or?/ (n = 60)

217 t 136 + 5.1 * 2.1 It

8 13 3 0.2

13 i- 10 95 * n

a fam-

No family h&or>, (n = ‘$8)

197 + 112 !I t59 + 1.6 f

6* 9 3 0.2t

111 +_ 7

97 L 2

Values are expressed as means ? SEM. *p < 0.O.Y +p < 0.0”.

hypertension (n = 48; 41 men, 7 women; 40 white, 4 black, and 4 Hispanic subjects). This information was based on careful questioning of participants; individuals who were uncertain of the presence or absence of hypertension in their first-degree relatives were not included in the study. Subjects with cardiovascular or other chronic illnesses were excluded from the study. All participants provided informed consent by signing a form that was approved by the Human Studies Subcommittee of the Veterans Affairs Medical Center in Long Beach. The patients came into the Hypertension Center at approximately 8~30 AM after a lo-hour fast. Histories were taken, and physical examinations were performed. A heparin lock was inserted into a peripheral vein of the left

forearm of each patient. After a 30-minute rest period in the supine position, blood samples were drawn from the heparin lock for measurements of catecholamines, glucose, insulin, lipids, plasma renin activity, and aldosterone. Two cardiopulmonary exercise treadmill tests, which were separated by an interval of 7 to 14 days, were performed by each patient. The first treadmill test (modified Balke-Ware protocol) was performed to allow patients to familiarize themselves with the procedure of exercise testing and to obtain a measurement of each patient’s maximal oxygen uptake. This measurement was used to individualize the second t.est. The second exercise test was

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