The utility of different definitions of metabolic syndrome in Andean population.
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Biomedical subjects
Publications and source records attributed to P López-Jaramillo.
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OBJECTIVE: To determine the effect of dietary supplementation of calcium plus conjugated linoleic acid (calcium-CLA) in reducing the incidence of vascular endothelial dysfunction in pregnant women at high risk of developing pregnancy-induced hypertension (PIH). PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled trial conducted at 4 outpatient clinics in 2 developing countries recruited 48 healthy primigravidas younger than 19 years or older than 35 years who had a family history of pre-eclampsia and diastolic notch. Twenty-four participants received daily elemental calcium (600 mg) plus CLA (450 mg) and 24 received placebo from week 18 to 22 of pregnancy until delivery. RESULTS: Calcium-CLA supplementation reduced significantly the incidence of PIH (2 cases [8%] in the study group vs. 10 cases [42%] in the placebo group; relative risk, 0.20; 95% confidence interval, 0.05-0.82; P=.01). Endothelial dysfunction was also significantly reduced after calcium-CLA supplementation (in 18 women [75%] vs. 4 women [17%]; P<.001), compared with the placebo group (in 15 [63%] vs. 9 women [38%]; P=.08). CONCLUSION: In pregnant women at high risk for PIH, calcium-CLA supplementation decreases the incidence of PIH and improves endothelial function.
OBJECTIVES: Pregnancy has been proposed as a risk factor for the development of osteoporosis; however, the results are controversial. Women in Colombia are multiparous, and therefore they represent an ideal population for the investigation of the effect of parity on osteoporosis. METHODS: The study included 1855 post-menopausal Hispanic women from Barranquilla, Colombia who were referred to our osteoporosis clinic for a routine evaluation of their bone mineral status. Bone mineral density (BMD, g/cm(2)) was measured using dual energy X-ray absorptiometry. Total body, femoral and lumbar areas were scanned. RESULTS: BMD of total body, hip and legs (P<0.0001), Ward's area (P<0.002) and intertrochanteric area (P<0.003) was high in women with at least one delivery in comparison with nulliparous women. Total mineral and calcium body contents were also high in women after second delivery. A history of fractures was found in 22.9% (n=425) of the study women. The relative risk for bone-fractures was high (O.R. 0.41; P<0.000002) in nulliparous women in comparison to multiparous women. In addition, osteopenia (O.R. 2.01; P=0.008) and osteoporosis (O.R. 3.99; P=0.0004) were most often present in nulliparous women in comparison to multiparous women. CONCLUSIONS: Pregnancies in this population appear to be a protective factor against development of osteoporosis. The increase in total mineral and calcium contents was related to the number of pregnancies, suggesting the existence of a bone mass peak during pregnancy.
The endothelium plays a crucial role in the pathogenesis of cardiovascular disease. Endothelial function is attenuated by the presence of different well known cardiovascular risk factors. Evaluation of endothelial vasodilator function serve as an index integrating the overall stress imposed by cardiovascular risk factors and reinforce the suggestion that endothelial dysfunction is an early marker of cardiovascular disease that precedes clinical manifestations. Angiotensin-converting enzyme inhibitors have been shown to reduce the cardiovascular mortality, an effect that could be the consequence of an improvement in the endothelial function. Recent studies have shown that a calcium antagonist might improve the endothelial function, however, there is controversy about this action and also about the potential mechanisms for the effect of a calcium antagonist in the regulation of endothelial function.
Nitric oxide (NO) is the principal vasoactive substance produced by the vascular endothelium with antitrombotic, antiatherogenic and vasodilator actions. The loss of these functions is now known as endothelial dysfunction (ED) and it has been proposed that it is the final common pathway in cardiovascular disease. At the moment there is an important body of evidence that supports the proposal that ED is a consequence of an imbalance between the free radicals, NO, superoxide (O(-)(2)) and peroxynitrate (ONOO(-)). This imbalance is the result of the actions of well known risk factors associated with an inappropriate diet and infection-inflammation. Angiotensin-converting enzyme (ACE) inhibitors are highly effective against a variety of cardiovascular disorders. Experimental and clinical studies have demonstrated a beneficial effect of ACE inhibition on endothelial function. This action is mainly due to an increase in the concentration of bradykinin, which stimulates NO production. ACE inhibitors also block the formation of angiotensin II that results in a lower production of O(-)(2). These effects lead to improve the imbalance between NO and O(-)(2) observed in cardiovascular disease. This proposal is supported by different clinical trials that have shown that the ACE inhibitors with higher affinity by the tissular ACE, such as quinapril, are the most effective in reversing ED principally by accumulating bradykinin. Recently, the HOPE study conducted in patients at a high risk of cardiovascular events, showed how ramipril, an ACE inhibitor with high affinity by tissular ACE, decreased the mortality rate due to cardiovascular disease independently of changes in blood pressure.
Recently in an open population-based program composed of 15 354 pregnant women in Colombia we applied a biopsychosocial risk model, which permitted us to identify pregnant women at high risk of preeclampsia. 1443 (9.4%) of patients at high risk for developing preeclampsia received 450 mg of linoleic acid, and 1.5 g/day of calcium. Bacteriuria was identified in 1766 (11.5%) and vaginal infections in 2150 (14.0%) of the pregnant women. These women received oral antibiotics for 10 days. The incidence of low birthweight, preterm delivery and preeclampsia were reduced by 53% (6.2% vs 13.2%), 64.7% (1.8% vs 5.1%), and 52.5% (3.8% vs 8.0%) respectively, when compared with the incidence of the preceding five years. We believe that these dramatic reductions were due to early identification of risk factors, administration of nutritional supplements and principally by treatment of asymptomatic infections. Unfortunately, because of the study design it is not possible to confirm that infection was the major risk factor for preeclampsia in our population. However, we hypothesize that chronic subclinical infections may cause increased maternal cytokine levels sufficient to affect vascular endothelial function, and so prime individuals for the subsequent development of preeclampsia. This hypothesis can be tested in a more appropriately designed clinical trial to assess whether there is a relationship between infection, inflammation and preeclampsia.
CONTEXT: C-reactive protein (CRP), predicts coronary heart disease incidence in healthy subjects and has been associated with decreased endothelium-dependent relaxation, a potential risk factor for hypertension. However, the relationship between CRP and hypertension has not been studied. OBJECTIVE: To assess whether circulating levels of CRP are independently related to essential hypertension. DESIGN: Cross-sectional population survey. We measured circulating levels of CRP, blood pressure and cardiovascular risk factors among participants. Binomial regression was used to calculate the adjusted effect of CRP on the prevalence of hypertension. SETTING: General community of Bucaramanga, Colombia. PARTICIPANTS: A random sample of 300 subjects > or = 30 years old. MAIN OUTCOME MEASURE: Arterial blood pressure. RESULTS: Overall hypertension prevalence was 46.0%. The unadjusted prevalence of hypertension was 58.7% in the highest quartile of CRP, but only 34.7% in the lowest quartile. After adjustment for age, sex, body mass index, family history of hypertension, fasting glycemia, sedentary behaviour, and alcohol consumption, the prevalence of hypertension was 1.14 [95% confidence interval (CI), 0.82, 1.58; P= 0.442], 1.36 (95% CI, 0.99, 1.87; P= 0.057) and 1.56 (95% CI, 1.14, 2.13; P = 0.005) times higher in subjects in the second, third and fourth quartiles of CRP, as compared to subjects in the first quartile. CONCLUSIONS: Our results suggest, for the first time, that CRP level may be an independent risk factor for the development of hypertension. However, because of the cross-sectional nature of our study, this finding should be confirmed in prospective cohort studies, aimed at elucidating the role of CRP in the prediction, diagnosis and management of hypertension.
An increase of coronary artery disease has been observed in developing countries during the last years. Various factors may explain this accelerated increase. We propose that inappropriate diet and inadequate sanitary infrastructure may act as triggers to create an imbalance between nitric oxide (NO) and superoxide (O2-). An increase in the concentrations of oxidized LDL produces both decreased NO and increased O2- endothelial synthesis, by accumulation of asymmetrical NG-NG-dimethyl-L-arginine, the endogenous inhibitor of NO, and by activation of NAD(P)H oxidase. On the other hand, high rates of chronic infection-inflammation, due to inappropriate sanitary environment stimulate higher circulating levels of proinflammatory cytokines. These cytokines also contribute to reduced NO and increased O2- endothelial production through the same mechanisms of oxidized LDL. The net result of this imbalance is an increased generation of peroxynitrate that injures the endothelium in a proatherogenic, prothrombotic and vasoconstrictive manner.
Preeclampsia is the main cause of maternal mortality and is associated with a five-fold increase in perinatal mortality in developing countries. In spite of this, the etiology of preeclampsia is unknown. The present article analyzes the contradictory results of the use of calcium supplementation in the prevention of preeclampsia, and tries to give an explanation of these results. The proposal of an integrative model to explain the clinical manifestations of preeclampsia is discussed. In this proposal we suggest that preeclampsia is caused by nutritional, environmental and genetic factors that lead to the creation of an imbalance between the free radicals nitric oxide, superoxide and peroxynitrate in the vascular endothelium. The adequate interpretation of this model would allow us to understand that the best way of preventing preeclampsia is the establishment of an adequate prenatal control system involving adequate antioxidant vitamin and mineral supplementation, adequate diagnosis and early treatment of asymptomatic urinary and vaginal infections. The role of infection in the genesis of preeclampsia needs to be studied in depth because it may involve a fundamental change in the prevention and treatment of preeclampsia.
The endothelium plays a critical role in vascular homeostasis. Recently, a noninvasive method has been developed to assess flow mediated vasodilatation of the brachial artery (FMD). This test is remarkably stable overtime but no clear set of normal values has been developed. The purposes of our study were to evaluate the accuracy and reproducibility and to identify a set of normal values of FMD. We included 253 normotensive healthy volunteers from three Colombian cities (mean age: 38.2 years; 33% were women). All subjects underwent ultrasound evaluation of endothelial and smooth muscle function. Flow mediated vessel diameter change was measured by two independent observers. The interobserver Lin's concordance correlation coefficient was 0.88% (95% CI: 0.82, 0.94) and there was no evidence of systematic difference between the two measurements (mean difference of -0.30% with limits of agreement of -4.48 to 3.87). Mean %FMD was 11.98% (95% CI: 11.36, 12.61), 13.32% (95% CI: 12.39, 14.25) in women and 11.32% (95% CI: 10.52, 12.13) in men. Subjects with no cardiovascular risk factors had a mean %FMD of 13.74% (95% CI: 13.14, 14.35), in contrast to a mean of only 7.40% (95% CI: 4.33, 9.91) in those with at least one risk factor. A %FMD cut point of 10.4 had a sensitivity of 71.2% and an specificity of 77.2% to identify subjects with at least one cardiovascular risk factor. Using this cut point, endothelial dysfunction was 3.13 times more frequent in subjects with than in subjects without cardiovascular risk factors (95% CI: 2.30, 4.25). In addition, obesity, smoking and hypercholesterolemia were the modifiable risk factors with largest independent significant reduction effects on %FMD. FMD measurements can be made with high accuracy and precision, and a cut point of 10.4% is useful to discriminate between subjects with and without cardiovascular risk factors, and can be recommended as a screening test for the detection of patients at risk of CVD.
A relationship between calcium dietary intake and incidence of preeclampsia was proposed. In the Andean Ecuadorian population, the average calcium intake, evaluated by a 24 hours dietary recall range between 52.3% of the US RDA to 77%. The calcium intake in women with preeclampsia was significantly lower in relation with normal pregnant women. Three prospective, randomized, double-blind, placebo-controlled clinical trials to investigate the effect of calcium supplementation (2 g/day of elemental calcium) in the incidence of pregnancy-induced hypertension and preeclampsia were conduced between 1984 and 1995. All the subjects included were nulliparous, younger that 25 years old, first prenatal visit before 24 weeks' gestation, residency in Quito, and normotensives. These clinical trials showed a risk reduction in pregnancy induced hypertension and preeclampsia in the calcium group. Calcium supplementation was associated with an increase in the serum ionized calcium concentrations. Moreover, women with preeclampsia showed a significant decrease in the levels of the serum ionized calcium. Ionic calcium is crucial for the synthesis of vasoactive substances in the endothelium as prostacyclin and nitric oxide. Recent results suggest that an alteration in the action of NO may be related to a high inactivation by free radical superoxide, secondary to an inflammatory process.
OBJECTIVE: Among white Dutch women pregnancy-induced hypertension was shown to be associated with elevated levels of the long-chain polyenes of 18:2n-6 and 18:3n-3 in combination with reduced levels of those parent essential fatty acids. This observation suggested an enhanced desaturation and elongation of the parent fatty acids. This study was performed to investigate whether this phenomenon also occurs under completely different nutritional and geographic conditions. STUDY DESIGN: Plasma fatty acids of primiparous Mestizo Ecuadorian women with uncomplicated pregnancies and with pregnancy-induced hypertension were assessed at delivery and compared with similar data from white Dutch women. Neonatal values, as determined in umbilical plasma and umbilical vessel walls, were also compared. RESULTS: In contrast to the pattern seen among white mothers, pregnancy-induced hypertension did not increase the long-chain polyene status of Mestizo mothers. Despite the absence of this compensatory mechanism, long-chain polyene status was not compromised in Mestizo neonates born after pregnancy-induced hypertension. CONCLUSION: Additional mechanisms may be active in maintaining the long-chain polyene status of neonates born after pregnancy-induced hypertension.
Estrogen promotes neurons growth, prevents neuronal cell atrophy and regulates synaptic plasticity. Administration of estrogen protects neurons against oxidative stress, excitotoxins, and beta-amyloid-induced toxicity in cell culture. It has been shown that estrogen treatment reduces the serum monoamino oxidase levels and might regulate learning and memory. Nitric oxide (NO) is a retrograde messenger and long-term potentiation can be block using NO-synthase inhibitors or can be prevent with NO-scavengers. NO synthase is widespread in the central nervous system and acts as neurotransmitter/neuromodulator. The actions of serotonin, bradykinin, endothelin, acetylcholine and noradrenaline might be linked to NO formation. Estrogen induces activity of constitutive NO synthase and estrogen replacement therapy in postmenopausal women increases significantly circulating nitrite plus nitrate levels. The effect of estrogen on NO synthesis is rapid and is maintained with repeated administration. We demonstrated the effects of estrogen replacement therapy in Andean postmenopausal women were associated with a significantly increase in plasma levels of nitrite plus nitrate. Our hypothesis is that beneficial effect of estrogen replacement therapy on involutive depression in postmenopausal women is mediated by increase in NO production by central nervous system.
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OBJECTIVE: To determine whether increased calcium intake (2 g/day) in pregnancy is effective in reducing the risk of preeclampsia in pregnant teenagers. METHODS: The present study was a prospective, randomized, double-blind, controlled clinical trial. Two hundred sixty teenaged pregnant girls attending the Hospital Gíneco-Obstétrico Isidro Ayora in Quito, Ecuador, were included. Selection criteria were age less than 17.5 years, nulliparity, first prenatal visit before 20 weeks' gestation, and residency in Quito (2800-m altitude). We used a table of random numbers to assign 125 girls to receive 2000 mg of elemental calcium daily, beginning at 20 weeks of gestation and continuing until delivery; 135 women in the control group received a placebo. Blood pressure (BP) was measured twice every 4 weeks until delivery and at 48 hours after delivery. The diagnosis of preeclampsia was defined as BP greater than 140/90 mmHg on at least two occasions more than 6 hours apart and proteinuria greater than 30 mg/dL (over one cross by dipstick on two occasions 4-24 hours apart). RESULTS: The average daily calcium intake in this population was approximately 51% of the Recommended Dietary Allowance. Calcium supplementation was associated with a significantly decreased risk of preeclampsia (risk reduction 12.35%; P < .001), with 3.2% (n = 4) developing preeclampsia in the treatment group versus 15.5% (n = 21) in the placebo group. Moreover, calcium supplementation led to a reduction in systolic BP of 9.1 mmHg and in diastolic BP of 6.0 mmHg. CONCLUSION: These results suggest that calcium supplementation during pregnancy in populations with low calcium intake is a safe, effective, and inexpensive preventive measure that significantly reduces the risk of preeclampsia.
OBJECTIVE: To investigate whether the steady decline in the maternal essential fatty acids (EFA) status during pregnancy observed in Dutch pregnant women is a local or general phenomenon. DESIGN: The EFA status was measured during uncomplicated, singleton pregnancy of healthy women from the Netherlands, Hungary, Finland, England and Ecuador. In addition, the EFA status of their neonates were measured at birth. Fatty acid profiles were analyzed in phospholipids isolated from maternal plasma and from umbilical plasma and cord vessel walls. RESULTS: Considerable differences between these centers were observed in the maternal EFA levels and EFA status indexes. However, the change in the absolute as well as relative amounts of the EFAs followed a similar course in the five populations during pregnancy. The neonatal EFA profiles reflected the differences found in maternal plasma during pregnancy and shortly after delivery. Comparable correlations were found, particularly, between the neonatal and the maternal n-3 fatty acids in the participating groups. CONCLUSIONS: It seems that the reduction in maternal EFA status during pregnancy is a general phenomenon, and is largely independent of differences in dietary habits and ethnic origin. Since the lowest values for certain maternal EFAs in a given country were significantly higher than the highest value of these EFAs throughout pregnancy in other countries, the functional implications of the pregnancy-associated reduction in the maternal EFA status for the fetal and neonatal development is not obvious and needs to be further elucidated.