Risk factors and carotid atherosclerosis in hypertensive and control subjects

Asko Rantala

Department of Internal Medicine and Biocenter Oulu, University of Oulu

Abstract

Different metabolic and environmental factors affect the blood pressure level, constituting a cluster, especially in hypertensives, that leads to an increased risk of cardiovascular diseases. The present research was designed to determine the prevalence and the predictors of the metabolic syndrome and the role of insulin and blood pressure in carotid atherosclerosis in 600 treated male and female hypertensives aged 40-59 years and 600 age- and sex-matched controls.

The prevalence of the metabolic syndrome in different population-based cohorts varied, depending on the definition, from 0.8% to 35.3%, being lowest in control men and women and highest in hypertensive men. 73.8% of a random, middle-aged, urban population showed at least one cardiovascular risk factor, and 91.3% of all hypertensive subjects showed at least one cardiovascular risk factor in addition to hypertension itself. The independent predictors of the metabolic syndrome were waist circumference, uric acid, total cholesterol and gamma-glutamyl transpeptidase. Hypertension had a significant effect on carotid intima-media thickness and the prevalence of plaques in men, but its effect in women was not significant. A long duration of hypertension resulted in greater intima-media thickness and a higher prevalence of plaques, particularly in men. There were significant associations between gamma-glutamyl transpeptidase and the components of the metabolic syndrome after adjustment for alcohol consumption and also in teetotallers. There were inconsistent associations between the different insulin measures and the intima-media thickness as a measure of carotid atherosclerosis. The exclusion of diabetic subjects did not change the results.

In conclusion, a cluster of metabolic abnormalities related to hypertension is frequent among both controls and treated hypertensive subjects. Hypertensive subjects have higher prevalences of carbohydrate and lipoprotein aberrations and structural and functional cardiovascular complications than age- and sex-matched controls.

Table of Contents

Acknowledgements

Abbreviations

List of original articles

1. Introduction

2. Review of the literature

2.1. Hypertension

2.1.1. Epidemiology: etiology, prevalence, incidence
2.1.2. Risk factors for cardiovascular disease in hypertension

2.2. Metabolic syndrome

2.2.1. Definition, prevalence, incidence
2.2.2. Lipid metabolism in insulin resistance
2.2.3. Insulin resistance in hypertension

2.3. Insulin resistance and gamma glutamyl transpeptidase

2.4. Carotid artery atherosclerosis determined by ultrasonography

2.5. Carotid atherosclerosis and hypertension

2.6. Insulin and carotid atherosclerosis

2.7. Heritability of the metabolic syndrome

3. Purpose of the study

4. Subjects and methods

4.1. Subjects

4.2. Methods

4.2.1. Clinical methods
4.2.2. Carotid ultrasonography
4.2.3. Laboratory analyses
4.2.4. Statistical analyses

5.1. Prevalence and predictors of the metabolic syndrome

5.1.1. Subjects and their basic characteristics
5.1.2. Prevalence of the metabolic syndrome
5.1.3. Predictors of the metabolic syndrome

5.2. GTP and the metabolic syndrome

5.3. Hypertension and carotid atherosclerosis

5.4. Hyperinsulinemia and carotid atherosclerosis

6. Discussion

6.1. Study population

6.2. Prevalence and predictors of the metabolic syndrome

6.2.1. Definition of the metabolic syndrome
6.2.2. Prevalence of the metabolic syndrome
6.2.3. Predictors of the metabolic syndrome

6.3. Association between insulin resistance and GTP

6.4. Carotid atherosclerosis in hypertensive and control subjects

6.4.1. Blood pressure and carotid atherosclerosis
6.4.2. Insulin and carotid atherosclerosis

7. Conclusions

List of Tables
1. Definitions of the characteristics of the metabolic syndrome in previous studies.
2. characteristics and cardiovascular risk factors of the hypertensive and control cohorts
3. Prevalence of the characteristics of the metabolic syndrome in the hypertensive and control cohorts
4. Prevalence of the metabolic syndrome by different definitions in the hypertensive and control cohorts
5. Multiple logistic models for independent variables of the metabolic syndrome adjusted for age, measure of obesity in each model and sex in all study subjects (n= 1045)
6. Pearson’s correlation coefficients between gamma GTP and cardiovascular risk factors in control and hypertensive men and women
7. Multiple stepwise regression analyses for independent variables of fasting serum insulin adjusted for body mass index , triglycerides, age, alcohol consumption and systolic blood pressure in control and hypertensive men and women
8. Maximal intima-media thicknesses (mm) and mean and maximal combined IMT+ plaque thicknesses (CombIMT) in the common carotid artery (CCA),bifurcation (BIF) and internal carotid artery (ICA) in hypertensive and control men and women.
9. Multiple stepwise regression analyses of the mean intima-media thickness with risk factors in control and hypertensive men and women

List of Figures
1. Correlations between gamma-GTP and BMI amongst the control men (left panel) and between gamma-GTP and plasma triglycerides amongst the hypertensive women (right panel).
2. Fasting and 2-hour glucose and insulin levels in the oral glucose tolerance test in gamma-GTP tertiles adjusted for age, BMI and alcohol consumption in the study groups. The tertile cut-off values were 19 U/L and 26 U/L in control women, 22 U/L and 38 U/L in hypertensive women, 27 U/L and 43 U/L in control men, and 33 U/L and 55 U/L in hypertensive men.
3. Moving mean curves showing maximal intima-media and plaque thickness at the internal/common carotid/bifurcation (CombIMT) in hypertensive and control men and women (1, control women; 2, women with hypertension; 3, control men; 4, men with hypertension.
4. Maximal intima-media and plaque thickness in control men (1) and in men with hypertension of duration < 7 years (2) and ≥ 7 years (3).
5. Moving mean curves showing the proportions of subjects with plaques (1, control women; 2, women with hypertension; 3, control men; 4, men with hypertension).
6. Moving mean curves showing the total number of plaques divided by the number of subjects in the group (1, control men; 2, men with hypertension of duration < 7 years; 3, men with hypertension of duration = 7 years).

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