Horacio A. Carbajal

Relation Among the Plasma Triglyceride/High-Density Lipoprotein Cholesterol Concentration Ratio, Insulin Resistance, and Associated Cardio-Metabolic Risk Factors in Men and Women

Results of recent studies using the ratio of plasma triglyceride (TG) to high-density lipoprotein (HDL) cholesterol concentration to identify insulin-resistant patients at increased cardiometabolic risk have emphasized that the cut point used for this purpose will vary with race. Because TG and HDL cholesterol concentrations vary with gender, this analysis was initiated to define gender-specific plasma TG/HDL cholesterol concentration ratios that best identified high-risk subjects among women (n = 1,102) and men (n = 464) of primarily European ancestry. Insulin resistance was defined as the 25% of the population with the highest values for fasting plasma insulin concentration and homeostasis model assessment of insulin resistance. Using TG/HDL concentration ratios >2.5 in women and >3.5 in men identified subgroups of men and women that were comparable in terms of insulin resistance and associated cardiometabolic risk, with significantly higher values for fasting plasma insulin, homeostasis model assessment of insulin resistance, blood pressure, body mass index, waist circumference, and glucose and TG concentrations and lower HDL cholesterol concentrations than in women and men below these cut points. The sensitivity and specificity of these gender-specific cut points to identify insulin-resistant subjects were about 40% and about 80%, respectively. In conclusion, the plasma TG/HDL cholesterol concentration ratio that identifies patients who are insulin resistant and at significantly greater cardiometabolic risk varies between men and women.

Relationships among insulin resistance, obesity, diagnosis of the metabolic syndrome and cardio-metabolic risk

The aim of this study is to test the hypotheses that: 1) diagnosing the metabolic syndrome does not effectively identify insulin-resistant (IR) individuals; and 2) waist circumference (WC) is no better than body mass index (BMI) in predicting insulin resistance or the components of the metabolic syndrome (MetS). Measurements of BMI, WC, blood pressure, and fasting plasma glucose, insulin (FPI), triglycerides (TG), and HDL-cholesterol (HDL-C) concentrations were made in 1,300 adults, without known cardiovascular disease (CVD) or drug treatment of hypertension or diabetes. Receiver operating characteristic curves were used to determine the ability of the MetS, and its components, to identify IR individuals. In addition, comparisons were made of CVD risk factors following division of the population into quartiles of FPI concentrations, and univariate and multiple regression analysis used to compare the ability of WC, BMI, and FPI as predictors of MetS components. The MetS was no more effective in identifying IR individuals than several individual components (sensitivity~40%), and IR individuals not identified were at significantly increased CVD risk. FPI concentration was the best predictor of an abnormal glucose, TG, and HDL-C, whereas the adiposity indices were better predictors of abnormal blood pressure. The relationship between BMI and WC with the MetS and its components seemed comparable.

Comparison of the abilities of the plasma triglyceride/high-density lipoprotein cholesterol ratio and the metabolic syndrome to identify insulin resistance

This study compares the ability of an elevated triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio, using sex-specific cut-points, to identify insulin-resistant individuals within a population without known cardiac disease or diabetes with that obtained using the diagnostic criteria of the metabolic syndrome (MetS). Measurements were made of waist circumference (WC), systolic and diastolic blood pressure, fasting plasma glucose, fasting plasma insulin (FPI), plasma TG and plasma HDL-C concentrations in 1102 women and 464 men. These data were used to classify subjects as being insulin resistant (FPI concentration in the upper quartile) and having the MetS or an elevated TG/HDL-C ratio (>2.5 and >3.5 for women and men, respectively). The sensitivity and specificity with which the two indices identified insulin-resistant subjects were similar (43% and 81% for TG/HDL-C ratio and 45% and 82% for MetS), as the number of individuals was found with either an elevated TG/HDL-C ratio (n = 386) or the MetS (n = 384). Eighty-one per cent of the individuals were identified concordantly. Cardio-metabolic risk profiles in ‘low-risk’ individuals identified by a low TG/HDL-C ratio were comparable to those who did not have the MetS, and this was also the case when comparing ‘high-risk’ groups identified by having the MetS or an elevated TG/HDL-C ratio. These findings suggest that TG/HDL-C concentration ratio is as adequate as MetS diagnosis to identify insulin-resistant subjects.

Significance of masked and nocturnal hypertension in normotensive women coursing a high-risk pregnancy.

Objective: The aim was to evaluate the prevalence of nocturnal and masked hypertension and the prognostic values of these blood pressure (BP) abnormalities in normotensive women coursing a high-risk pregnancy. Methods: The study was performed in pregnant women with 20 or more weeks of gestation coursing a high-risk pregnancy, sent to a specialized hypertension department to perform a prospective defined protocol of BP evaluation. Women with office BP at least 140/90 mmHg were excluded. An ambulatory monitoring of BP was performed to identify masked and nocturnal hypertension (defined according to the current guidelines). The adjusted risk for development of preeclampsia/eclampsia (PEEC) was estimated using logistic regression. The ability of SBP and DBP to identify risk of PEEC was estimated using area under the receiver-operating characteristic curves. Results: Eighty-seven women (29 ± 7 years old, 30 ± 5 weeks of pregnancy) were included in this analysis. The prevalence of masked hypertension was 33.3%. Nocturnal hypertension was found in 42.5% of the women. Remarkably, 27.0% of the women with nocturnal hypertension had normal 24-h values according to ambulatory BP monitoring. Twenty-two patients developed PEEC; adjusted relative risks increased with the presence of nocturnal (odds ratio = 4.72, 95% confidence interval 1.25–19.43, P = 0.023) or masked hypertension (odds ratio = 7.81, 95% confidence interval 2.6–22.86, P = 0.001). Nocturnal SBP and DBP had the highest abilities to predict PEEC (area under the curve = 0.77 and 0.80, respectively). Conclusion: Masked and nocturnal hypertension are frequent findings in normotensive women coursing a high-risk pregnancy, and their presence implies an increased risk to develop PEEC.

Insulin resistance: The linchpin between prediabetes and cardiovascular disease.

The aim of this study was to test the hypothesis that cardiovascular disease occurs to the greatest extent in persons with prediabetes mellitus who are also insulin resistant. In 2003, 664 non-diabetic women (n = 457) and men (n = 207), aged 52 ± 16 and 53 ± 15 years, were surveyed during a programme for cardiovascular disease prevention. Fasting plasma glucose concentrations defined participants as having normal fasting plasma glucose (fasting plasma glucose <5.6 mmol/L) or prediabetes mellitus (fasting plasma glucose ⩾5.6 and <7.0 mmol/L). The tertile of prediabetes mellitus subjects with the highest fasting plasma insulin concentration was classified as insulin resistant. Baseline cardiovascular disease risk factors were accentuated in prediabetes mellitus versus normal fasting glucose, particularly in prediabetes mellitus/insulin resistant. In 2012, 86% of the sample were surveyed again, and the crude incidence for cardiovascular disease was higher in subjects with prediabetes mellitus versus normal fasting glucose (13.7 vs 6.0/100 persons/10 years; age- and sex-adjusted hazard ratio = 1.88, p = 0.052). In prediabetes mellitus, the crude incidences were 22.9 versus 9.6/100 persons/10 years in insulin resistant versus non-insulin resistant persons (age- and sex-adjusted hazard ratio = 2.36, p = 0.040). In conclusion, cardiovascular disease risk was accentuated in prediabetes mellitus/insulin resistant individuals, with a relative risk approximately twice as high compared to prediabetes mellitus/non-insulin resistant subjects.

Blood Pressure Response to a Community-Based Program and Long-term Cardiovascular Outcome

BACKGROUND The significance in terms of the cardiovascular outcome of different patterns of blood pressure (BP) response to community-based activities has not been previously studied. The aim of our study was to evaluate the relationship between changes of BP observed during a community-based program and long-term rate of cardiovascular disease (CVD) events. METHODS A program focused on the prevention of CVDs was implemented in a small city in Argentina over a 6-year period (1997-2003). The program was evaluated using a cohort of 1,526 randomly selected individuals. The populations mean systolic BP (SBP) decreased approximately 5mm Hg, but BP changes were heterogeneous. Eight years after the intervention had stopped, 1,124 individuals of the cohort were surveyed to evaluate incident CVD events. The sample was divided into 3 SBP change categories during the intervention: decrease (< -5mm Hg), no change (-5 to 5mm Hg) and increase (> 5mm Hg). Cox models were used to estimate the hazard ratio (HR) of CVD events for each category adjusted for age, sex, and baseline BP. RESULTS At the end of the intervention, individuals who had increased their SBP showed an adjusted HR for CVD that was double those whose SBP levels decreased or did not change. An inverse relationship between baseline SBP and ΔSBP was observed: individuals with an increase in BP during the intervention had lower SBP at the beginning of the study. CONCLUSIONS BP increase during the community-based program was an independent predictor of CVD events.

Do Differences in Waist Circumference Modify the Relationships Among Body Mass Index, Insulin Resistance, and Related Cardiometabolic Risk Factors in Apparently Healthy Women?

Objective: The aims of the study were to (1) compare the cardiometabolic risk profile between insulin-resistant and non-insulin-resistant women within similar body mass indexes (BMIs) and waist circumference (WC) groupings and (2) test the hypothesis that measurements of BMI are not inferior to WC in identifying insulin resistance. Methods: The sample consisted of 899 women without known cardiovascular disease or diabetes. BMI was used to divide participants in normal (<25.0 kg/m2), overweight (≥25–29.9 kg/m2), and obese (≥30.0 kg/m2) subgroups, and waist circumference ≥88 cm was used to identify women with or without abdominal obesity. The 25% of the population with highest fasting insulin concentrations was classified as insulin resistant. BMI, WC, blood pressure, and fasting plasma glucose, insulin, triglyceride, and high-density lipoprotein cholesterol concentrations were compared using analysis of covariance (ANCOVA). The relationships between obesity and insulin resistance were analyzed using univariate, multivariate, and logistic regression. Results: Triglyceride and glucose concentrations were higher and high-density lipoprotein cholesterol concentrations lower in the insulin-resistant group in each BMI category, as was the case when comparing by abdominal obesity. In the univariate analysis, correlations between obesity and the individual cardiometabolic risk factor were significant but weak. In multivariate analysis including both indices, only body mass independently predicted insulin resistance. Conclusion: Insulin-resistant women were at greater cardiometabolic risk, irrespective of adiposity category. Obesity contributed to a modest variability in insulin resistance, and abdominal obesity does not add to the ability of BMI to predict insulin resistance.

Optimal Uric Acid Threshold to Identify Insulin Resistance in Healthy Women

BACKGROUND Identifying insulin-resistant (IR) individuals is an issue of particular interest in the assessment of cardiometabolic risk, but there is no simple way to accomplish this task. Our aims were to determine the relationship between uric acid and insulin resistance and to define the optimal uric acid cutoff to identify insulin resistance in women. METHODS A population-based sample of 588 women without cardiovascular diseases, diabetes, or low glomerular filtration rate (GFR) was divided according to uric acid tertiles. Systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), TG/HDL-C ratio, insulin [fasting plasma insulin (FPI)], and homeostasis model assessment of insulin resistance (HOMA-IR) were compared between the mentioned tertiles. Receiver operating characteristic (ROC) curves were constructed to determinate the optimal cutoff of uric acid and identify IR individuals defined by the top tertile of FPI and HOMA-IR. The same variables were compared using the top tertile of uric acid and the maximum Youden index as cutoffs. The P values were adjusted by age, GFR, and body mass index (BMI) using analysis of covariance (ANCOVA). RESULTS FPI, HOMA-IR, and all of the cardiometabolic risk factors increased through uric acid tertiles. Both cutoffs of uric acid, estimated by the top tertile and by ROC, were identical (4.0 mg/dL). FPI, HOMA-IR, SBP, DBP, TG, TG/HDL-C ratio, and fasting glucose were higher, whereas HDL-C was lower in women who had uric acid levels >4.0 mg/dL. All of the differences remained significant after the adjustment by age and GFR. CONCLUSION In healthy women, uric acid levels >4.0 mg/dL were associated with all the markers of IR.

Use of the triglyceride/high-density lipoprotein cholesterol ratio to identify cardiometabolic risk: impact of obesity?

There is evidence that the plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) identifies insulin resistance and increased cardiometabolic risk and outcome in apparently healthy individuals. Since use of the TG/HDL-C ratio to accomplish this task in persons over a wide range of adiposity has not been studied, the ability of previously defined sex-specific TG/HDL-C cut-points to identify increased cardiometabolic risk was evaluated in apparently healthy normal weight, overweight, and obese individuals. Data were analyzed from a population-based study of apparently healthy men (n=416) and women (n=893), subdivided into categories by body mass index (BMI, kg/m2): normal weight (BMI 20.0–24.9), overweight (BMI 25.0–29.9) and obese (BMI 30.0–34.9). The adiposity groups were further stratified on the basis of their TG/HDL-C ratio into groups defined as being either at ‘high risk’ versus ‘low risk’ of cardiometabolic disease. Multiple cardiometabolic risk factors were compared between these subgroups, as was their degree of insulin resistance assessed by fasting plasma insulin concentration and homeostasis model assessment of insulin resistance. The proportion of high-risk individuals varied with BMI category, ranging from 14% (normal weight) to 36% (obese). However, within each BMI category high-risk individuals had a significantly more adverse cardiometabolic risk profile. Finally, the adjusted OR of being insulin resistant was significantly greater in those with a high TG/HDL-C ratio in the normal (3.02), overweight (2.86), and obese (2.51) groups. Thus, irrespective of differences in BMI, the TG/HDL-C ratio identified apparently healthy persons with a more adverse cardiometabolic risk profile associated with an increased prevalence of insulin resistance.