(Hypertension. 1995;26:1085-1088.)
© 1995 American Heart Association, Inc.
Articles |
Serum Insulin Levels, 24-Hour Blood Pressure Profile, and Left Ventricular Mass in Nonobese Hypertensive Patients
From the Endocrinology and Hypertension Divisions, Escola Paulista de Medicina, Federal University of São Paulo (Brazil).
Correspondence to Maria-Teresa Zanella, MD, Endocrinology Division, Escola Paulista de Medicina, UNIFESP, Rua Botucatu 720, Vila Clementino, São Paulo, SP, Brazil, 04023-009.
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Abstract |
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Abstract In essential hypertensive patients, considered to be insulin-resistant, a blunted decline in nocturnal blood pressure is associated with increased adrenergic tone and left ventricular mass. Since insulin stimulates the sympathetic system, we tested whether insulin resistance and insulinemia influence left ventricular mass and the 24-hour blood pressure profile. We studied 29 nonobese hypertensive patients with office diastolic pressure between 95 and 110 mm Hg and normal oral glucose tolerance test after a 4-month washout period. They were then assigned to M-mode echocardiographic evaluation and 24-hour ambulatory blood pressure monitoring. The glucose and insulin responses to a 75-g oral glucose load were compared with those obtained in 16 weight-matched normotensive control subjects. During the oral glucose tolerance test the hypertensive patients compared with control subjects presented higher levels of glucose at 60 minutes (138.7±30.3 versus 108.7±35.7 mg/dL; P<.05) and 90 minutes (114.0±23.8 versus 94.8±31.1 mg/dL; P<.05) and insulin at 60 minutes (287.1±259.4 versus 142.1±83.9 pmol/L; P<.05). However, peak insulin levels after glucose load did not correlate with ambulatory blood pressure values or left ventricular mass index. Left ventricular mass index showed significant correlation with mean sleeping systolic pressure (rs=.56, P<.05) and diurnal systolic pressure (rs=.37, P<.05) but not with mean diurnal or sleeping diastolic pressures. In conclusion, our results indicate that in nonobese hypertensive patients, insulin resistance does not have any influence on the 24-hour blood pressure profile or on left ventricular mass index. Blood pressure levels during sleep in these patients seem to contribute to increases in left ventricular mass.
Key Words: left ventricular mass index • blood pressure monitoring, ambulatory • hypertension, essential • insulin resistance • echocardiography
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Introduction |
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Hypertension has already been reported as a state of insulin resistance.1 2 This insulin insensitivity in essential hypertension is restricted to nonoxidative metabolism into the peripheral tissues independent of the presence of obesity.3 4 The presence of these two conditions is associated with elevated cardiovascular morbidity.
LV hypertrophy, as well as high BP levels and abnormalities in lipid and glucose metabolism, is an important risk factor for cardiovascular events in essential hypertension. Some studies have shown that mean 24-hour ambulatory BP values correlate better with LVM than office BP values.5 6 7 Furthermore, hypertensive individuals with a blunted BP fall during sleep are prone to the development of LV hypertrophy.8 9 This pattern of a reduced nocturnal decline in BP has been associated with a predominant adrenergic tone during sleep.10 Since hyperinsulinemia increases sympathetic activity,11 12 insulin resistance and increased levels of plasma insulin could be involved in reductions of the nocturnal BP fall, thus contributing to the development of LV hypertrophy.
We designed this study to investigate the role of insulin resistance on BP profile and LVM in a group of nonobese essential hypertensive patients.
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Methods |
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We studied 29 hypertensive outpatients (15 women, 14 men) followed at the Hypertension and Diabetes Clinic of Universidade Federal de São Paulo. All patients provided written consent before entry, and the study was approved by the Ethics Committee of Escola Paulista de Medicina. Patients were kept off antihypertensive drugs for at least 4 months and were included in the study if they had a mean of three seated diastolic BP measurements between 95 and 110 mm Hg in at least two clinic visits. The selection criteria included age between 18 and 65 years; body mass index less than 30 kg/m2; and absence of clinical or laboratory evidence of cardiopulmonary, renal, or hepatic disease. Subjects with abnormal OGTT or other endocrinopathies were excluded.
Oral Glucose Tolerance Test
From the 29 hypertensive patients and 16 weight-matched
normotensive control subjects (8 women, 8 men), fasting blood samples
were taken for determination of high-density lipoprotein,
low-density lipoprotein, and total cholesterol levels
and triglycerides. Plasma glucose and insulin values were
obtained before and every 30 minutes after a 75-g oral glucose overload
(OGTT). Plasma glucose responses to the OGTT were interpreted according
to the National Diabetes Data Group criteria.13
Glucose-intolerant or diabetic patients were excluded from the
study. For each subject in the hypertensive or control group we
determined the peak of plasma insulin levels (PPI) and corresponding
plasma glucose (PG) after glucose load and calculated an index of
insulin resistance (IRI) based on the formula
IRI=PPIxPGx10-4.14
Assays
Plasma glucose was measured by the glucose-oxidase method,
and serum lipids were determined by an enzymatic
colorimetric method. Insulin was evaluated by an
immunofluorometric assay with two monoclonal antibodies, where the
second antibody does not react with intact proinsulin, split
32-33 proinsulin, and des 31-32 proinsulin. The within- and
between-assay coefficients of variation were 10% and 13%,
respectively.15
Echocardiographic Measurements
M-mode bidimensional echocardiograms with pulsed Doppler
were performed in hypertensive patients with the use of an Esaote
Biomédica system (SIM 5000 model) with a 2.5-MHz mechanical
transducer. LV measurements were made according to the recommendations
of the American Society of Echocardiography.
LVM was calculated with the equation LVM=0.8{1.04[(IVSd+LVIDd+PWd)3-(LVIDd)3]}+0.6 g, where IVSd is interventricular septal thickness at end diastole, LVIDd is LV internal dimension at end diastole, and PWd is posterior wall thickness at end diastole.16 LVMI was calculated by dividing the value of LVM by body surface area. The upper limits of normal of LVMI were 134 g/m2 for men and 110 g/m2 for women.17
24-Hour ABPM
All hypertensive patients were assigned to 24-hour ABPM by the
oscillometric method. A portable SpaceLabs 90207 monitor was linked
through a cuff to the patient's nondominant arm and was programmed to
record at 15-minute intervals during the awake period and at
30-minute intervals during sleep. Reading, editing, and
analysis of the records were executed by an interface
(SpaceLabs 90219) connected to a personal microcomputer. The patients
were advised to perform their habitual activities and take notes in a
personal diary, including their sleeping and waking times. The means of
all BP values during awake, sleeping, and 24-hour periods were
calculated. The exams presenting more than 20% error were
repeated.
Statistical Analysis
Student's t test and the Mann-Whitney U
test were used for comparisons between groups where appropriate.
Spearman's coefficient was calculated to test for a correlation
between two variables. A value of P<.05 was considered
significant.
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Results |
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Table 1 shows anthropometric, metabolic, and office BP characteristics of hypertensive and normotensive groups, and Table 2 shows the BP means of each period of the 24-hour ABPM in hypertensive patients. The hypertensive patients presented low-density lipoprotein and total cholesterol levels higher than the normotensive subjects. Fig 1 shows that during the OGTT plasma glucose levels were significantly higher in hypertensive patients at 60 and 90 minutes (138.7±30.3 versus 108.7±35.7 and 114.0±23.8 versus 94.8±31.1 mg/dL, respectively; P<.05). As shown in Fig 2 fasting insulin was similar in both groups, but insulin became significantly higher 60 minutes after the glucose load in hypertensive patients than in normotensive subjects (287.1±259.4 versus 142.1±83.9 pmol/L; P<.05). Insulin resistance index was higher in the hypertensive group than in the control group (4.9±4.4 versus 2.3±1.7 pmol·µg-1·L-2, P=.01). However, no correlations were found between peak insulin values or insulin resistance index and diurnal or sleeping systolic and diastolic BP values in the hypertensive group.
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When hypertensive patients were analyzed on the basis of the effect of their BP levels on LVM, we found 31% of them (9 of 29) with LVMI higher than the normal limits. The mean value of LVMI in the entire group of hypertensive patients was 111.3±19.4 g/m2. LVMI presented a direct relation with systolic BP levels, particularly with regard to the sleeping period. LVMI correlated with 24-hour systolic BP (rs=.39, P<.05), with diurnal systolic BP (rs=0.37, P<.05), and with sleeping systolic BP (rs=.58, P<.05) (Fig 3). LVMI did not correlate with diastolic BP values during any time of ABPM.
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No significant correlations were found between peak insulin levels and LVMI (rs=-.005, P=NS) or between insulin resistance index and LVMI (rs=-.098, P=NS).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The presence of insulin resistance in essential hypertension has been demonstrated, and this metabolic disorder may contribute to the morbidity of hypertension.18 In the present study the increased plasma insulin and glucose levels in nonobese, non–glucose-intolerant hypertensive patients indicate the occurrence of insulin resistance associated with hypertension. Furthermore, in this study the insulin levels were not overestimated by proinsulin cross-reaction, because a specific immunofluorometric assay for true insulin was used.
The causal relationship between insulin resistance and hypertension is still controversial, despite the fact that these conditions are frequently found together.19 20 Insulin has been reported to increase BP through its effects on renal sodium retention,21 22 sympathetic nervous system stimulation,11 12 renin-angiotensin-aldosterone system activation,23 and growth factor action24 25 as well as its influence on cellular membrane cation transport.26 On the other hand, the increased adrenergic tone in hypertension might contribute to decreases in insulin sensitivity. Regardless of this possible cause-effect relationship, many reports have been successful in demonstrating a direct correlation between insulin levels and BP.27 In the present study, however, we found no correlation between these variables. This could be due to the narrow limits of BP observed in our group of nonobese mildly hypertensive patients and could also relate to the method of evaluation of insulin resistance. Although more practical and suitable for clinical purposes,28 the OGTT could not estimate insulin resistance as well as other laboratory methods, such as the hyperinsulinemic clamp.
The role of high BP levels in the development of myocardial hypertrophy has been documented. Studies with 24-hour ABPM have demonstrated that these BP values correlated better with LVM than office BP.5 6 7 The present study points to the importance of elevated sleeping BP as a factor contributing to the increase of LVM in hypertensive patients.9 29 In these patients there may be a threshold of sleeping BP above which the risk of development of myocardial hypertrophy is increased. Thus, it may be important to maintain BP below a certain limit to diminish the risk of cardiovascular events.
Theoretically, insulin resistance or hyperinsulinemia could affect cardiac mass directly, acting on insulin growth factor receptors,24 25 or indirectly, stimulating adrenergic tone and increasing BP levels.30 The abnormality in the pattern of BP decrease related to sleep could be the link between hyperinsulinemia31 and the development of myocardial hypertrophy in insulin-resistant hypertensive patients. However, our results have failed to demonstrate a relationship between insulin levels and LVM, although this has been described in two previous studies that included more obese subjects.32 33 This difference could be attributed to the mild degree of hyperinsulinemia in our patients.
In summary, the present study confirms the presence of insulin resistance in nonobese essential hypertensive patients. Our results indicate that the occurrence of mild insulin resistance in nonobese hypertensive patients has no marked influence on the pattern of daily BP and LVM and point out the importance of sleeping BP levels in the development of myocardial hypertrophy.
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Selected Abbreviations and Acronyms |
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Received June 19, 1995; first decision September 16, 1995; accepted October 13, 1995.
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