No difference in acute effects of supplemental v. dietary calcium on blood pressure and microvascular function in obese women challenged with a high-fat meal: a cross-over randomised study.

Recent studies suggest that supplemental Ca (SC) increases the risk of cardiovascular events, whereas dietary Ca (DC) decreases the risk of cardiovascular events. Although frequently consumed with meals, it remains unclear whether Ca can mitigate or aggravate the deleterious effects of a high-fat meal on cardiovascular risk factors. This study aimed to evaluate the effects of SC or DC on blood pressure (BP) and microvascular function (MVF) in the postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20-50 years were randomly assigned to receive three test meals (2908 kJ (695 kcal); 48 % fat): high DC (HDCM; 547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (LCM; 42 mg DC). BP was continuously evaluated from 15 min before to 120 min after meals by digital photoplethysmography. Before and 120 min after meals, participants underwent evaluation of serum Ca and microvascular flow after postocclusive reactive hyperaemia (PORH) by laser speckle contrast imaging. Ionised serum Ca rose significantly only after HSCM. Systolic BP increased after the three meals, whereas diastolic BP increased after LCM and HDCM. Hyperaemia peak, hyperaemia amplitude and AUC evaluated after PORH decreased with LCM. After HDCM, there was a reduction in hyperaemia peak and hyperaemia amplitude, whereas HSCM decreased only hyperaemia peak. However, comparative analyses of the effects of three test meals on serum Ca, BP and MVF revealed no significant meal×time interaction. This study suggests that in obese women SC and DC do not interfere with the effects of a high-fat meal on BP and MVF.

The effects of moderate energy restriction on apnoea severity and CVD risk factors in obese patients with obstructive sleep apnoea.

Nutritional intervention for weight loss is one of the treatment options for obstructive sleep apnoea (OSA) in patients with overweight or obesity. However, the effects of moderate energy restriction on OSA severity are not yet known. The present study aimed to evaluate the effects of moderate energy restriction on OSA severity and CVD risk factors in obese patients with OSA. In this 16-week randomised clinical trial, twenty-one obese subjects aged 20-55 years and presenting an apnoea/hypopnoea index (AHI)≥5 events/h were randomised into two groups: the energy restriction group (ERG) and the control group (CG). The ERG was instructed to follow an energy-restricted diet -3347·2 kJ/d (-800 kcal/d) and the CG was advised not to change their food intake. At the beginning and at the end of the study, participants underwent evaluation of the following: OSA (Watch-PAT200®), nutritional parameters, blood pressure, sympathetic activity, inflammatory biomarkers, metabolic profile and endothelial function. The ERG (n 11), compared with the CG (n 10), had a significantly greater reduction in body weight (Cohen's d=-1·19; P<0·001), in AHI (Cohen's d=-0·95; P=0·04) and in plasma concentrations of adrenaline (Cohen's d=-1·02; P=0·04) as well as a significantly greater increase in minimum O2 saturation (Cohen's d=1·08; P=0·03). Although energy restriction was not associated with significant improvements in CVD risk factors, medium-to-large effect sizes were observed, suggesting that the statistically non-significant difference between groups may be due to the small sample size. This study suggests that in obese patients with OSA, moderate energy restriction is able to reduce the parameters of OSA severity and sympathetic activity.

Obstructive sleep apnea is independently associated with inflammation and insulin resistance, but not with blood pressure, plasma catecholamines, and endothelial function in obese subjects.

OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease (CVD). Several of the proposed mechanisms for the development of CVD in OSA are similar to those proposed for the increased risk of CVD in obesity, so that it is difficult to determine the influence of OSA on these pathogenic mechanisms in obese individuals. The aim of this study was to evaluate the relationship of OSA with endothelial function, oxidative stress, inflammatory biomarkers, metabolic profile, sympathetic nervous system activity, and blood pressure (BP) in obese individuals. METHODS: This cross-sectional study included 53 obese adults (28 women). Sleep study was performed with WatchPAT 200 (Itamar Medical, Caesarea, Israel) and the diagnosis of OSA was made when apnea-hypopnea index (AHI) ≥5 events/h (n = 33). All participants underwent evaluation of: body adiposity, BP, plasma catecholamines, high sensitivity C-reactive protein (hs-CRP), adiponectin, malondialdehyde, glucose, insulin, lipid profile, and endothelial function (EndoPAT 2000). RESULTS: In univariate analysis, participants with OSA compared with those without OSA exhibited higher values of neck circumference, glucose, noradrenaline, and systolic BP. After adjustment for confounders, including adiposity, only glucose and hs-CRP were significantly higher in OSA patients. In correlation analysis, after controlling for confounders, AHI was positively and significantly associated with neck circumference and hs-CRP, while minimum O2 saturation was associated negatively and significantly with neck circumference, insulin and homeostatic model assessment-insulin resistance (HOMA-IR). CONCLUSIONS: The present study suggests that in obese individuals OSA is independently associated with inflammation and insulin resistance, but not with BP, plasma catecholamines and endothelial function.

Vitamin d deficiency is associated with insulin resistance independent of intracellular calcium, dietary calcium and serum levels of parathormone, calcitriol and calcium in premenopausal women.

BACKGROUND: There is evidence that vitamin D deficiency is associated with increased risk of cardiovascular disease. However, it is not known if this association is independent of dietary calcium, intracellular calcium and serum levels of parathormone, calcitriol and calcium. OBJECTIVES: To investigate the independent relationship of vitamin D deficiency with insulin resistance, lipid profile, inflammatory status, blood pressure and endothelial function. METHOD: Cross-sectional study conducted with 73 healthy Brazilian premenopausal women aged 18 - 50 years. All participants were evaluated for: 25 hydroxyvitamin D serum levels, anthropometric parameters, body composition, calcium metabolism, insulin resistance, lipoprotein profile, inflammatory status, blood pressure and endothelial function. Endothelial function was assessed by reactive hyperemia index using Endo-PAT 2000®. Women were stratified in two groups: with vitamin D deficiency (25 hydroxyvitamin D < 20 ng/ml; n=12) and without vitamin D deficiency (25 hydroxyvitamin D ≥ 20 ng/ml; n=61). RESULTS AND DISCUSSION: Participants with vitamin D deficiency compared with those without deficiency of this vitamin had significantly higher levels of glucose (88.25 ± 3.24 vs. 80.15 ± 1.13 mg/dl), greater HOMA-IR (6.43 ± 0.73 vs. 4.42 ± 0.25) and lower reactive hyperemia index (1.68 ± 0.1 vs. 2.17 ± 0.1). After adjustments for confounding factors including age, body mass index, waist circumference, dietary calcium, intracellular calcium and serum levels of parathormone, calcitriol and calcium differences between groups remained significant, regarding glucose and HOMA-IR. CONCLUSIONS: The findings of the present study suggest that vitamin D deficiency is associated with insulin resistance independent of dietary calcium, intracellular calcium and serum levels of parathormone, calcitriol and calcium in healthy premenopausal women.

Introducción: Hay evidencias de que la deficiencia de vitamina D se asocia con mayor riesgo de enfermedad cardiovascular. Sin embargo, no se sabe si esta asociación es independiente de calcio en la dieta, el calcio intracelular y los niveles séricos de hormona paratiroidea, calcitriol y calcio. Objetivos: investigar la relación independiente de la deficiencia de vitamina D con resistencia a la insulina, el perfil lipídico, el estado inflamatorio, la presión arterial y la función endotelial. Métodos: Estudio transversal realizado con 73 mujeres pre menopáusicas sanas brasileñas con edad 18-50 años. Todos los participantes fueron evaluados para: niveles séricos de 25 hidroxivitamina D, parámetros antropométricos, la composición corporal, metabolismo del calcio, resistencia a la insulina, el perfil de lipoproteínas, estado inflamatorio, la presión arterial y la función endotelial. La función endotelial fue evaluada por el índice de hiperemia reactiva mediante el uso de Endo-PAT 2000®. Las mujeres fueron estratificados en dos grupos: con deficiencia de vitamina D (25 hidroxivitamina D.

Adiposity and cardiovascular disease risk factors in renal transplant recipients: Are there differences between sexes?

OBJECTIVE: The aim of this study was to evaluate high body adiposity and cardiovascular disease (CVD) risk factors prevalence, in renal transplant recipients (RTR), comparing men with women. METHODS: In this retrospective cross-sectional study, 102 patients (55 men) who were 49 ± 1.2 y and 114.3 ± 9 mo post-transplant (post-tx) were evaluated. Pretransplant (pre-tx) period data and weight gain during the first year post-tx were obtained from patient charts and post-tx data were collected during a routine visit at nephrology clinic. Body mass index (BMI) ≥ 25 kg/m(2) defined overweight and BMI ≥ 30 kg/m(2) defined obesity. RESULTS: Pre-tx overweight prevalence was low and similar between men and women (26%), whereas only women showed obesity (11%). Post-tx body weight increased significantly in the entire group, leading to an increase in overweight (to 38% in men and 51% in women) and obesity (to 11% in men and 23% in women) prevalence. Post-tx comparisons between men and women showed that women had higher (women versus men; P < 0.05) BMI values (26.7 ± 0.8 versus 24.7 ± 0.5 kg/m(2)), weight gain during first year post-tx (9.2 ± 1.1 versus 5.5 ± 1 kg), abdominal obesity (57% versus 23%) and diabetes (34% versus 16%) prevalence. The associations between adiposity and CVD risk factors showed that pre-tx overweight increased the risk for diabetes in post-tx; pos-tx high BMI and abdominal obesity increased the risk for metabolic syndrome; abdominal obesity increased the risk for dyslipidemia in women. CONCLUSIONS: High body adiposity prevalence was high after transplantation and increased the risk for metabolic syndrome, an important CVD risk factor. Women showed higher total body adiposity values, abdominal obesity, and diabetes prevalence than men. Abdominal obesity increased the risk for dyslipidemia in women.

Dietary calcium intake is associated with adiposity, metabolic profile, inflammatory state and blood pressure, but not with erythrocyte intracellular calcium and endothelial function in healthy pre-menopausal women.

Recent studies have suggested that dietary Ca may have beneficial effects on adiposity, insulin resistance, dyslipidaemia and blood pressure (BP). One potential mechanism underlying these benefits involves modifications in intracellular Ca concentration ([Ca2+]i). The present study aimed to evaluate the associations of dietary Ca with adiposity, erythrocyte [Ca2+]i, metabolic profile, BP, inflammatory state and endothelial function in healthy pre-menopausal women. In the present cross-sectional study, seventy-six women aged 18­50 years were submitted to the evaluation of dietary intake, anthropometric parameters, body composition, erythrocyte [Ca2+]i, biochemical variables, endothelial function and BP. A FFQ was used to assess usual dietary intake. Endothelial function was evaluated by serum concentrations of adhesion molecules and by the peripheral arterial tonometry (PAT) method, using Endo-PAT 2000®. Participants were allocated into two groups according to Ca intake: low-Ca group (LCG; n 32; < 600 mg/d) and high-Ca group (HCG; n 44; ≥ 600 mg/d). Women in the LCG compared with those in the HCG exhibited, after adjustments for potential confounders, higher values of BMI, waist circumference, waist:height ratio, percentage of body fat, insulin, homeostasis model assessment of insulin resistance, leptin, diastolic and mean BP; and lower levels of HDL-cholesterol, adiponectin and vascular cell adhesion molecule 1. Endothelial function assessed by PAT and [Ca2+]i was similar in both groups. Subjects in the HCG had lower OR for prevalent overweight, obesity, abdominal obesity, insulin resistance, HDL-cholesterol < 600 mg/l and systolic BP >120 mmHg. The findings of the present study suggest that high Ca intake is inversely associated with some cardiovascular risk factors.

Effects of weight loss from a high-calcium energy-reduced diet on biomarkers of inflammatory stress, fibrinolysis, and endothelial function in obese subjects.

OBJECTIVE: Obesity is characterized by chronic subclinical inflammation, which is critical to endothelial dysfunction. Weight loss, induced by lifestyle interventions, is associated with a decline in biomarkers of inflammation and endothelial dysfunction. There is little evidence that high dietary calcium intake may reduce inflammation and improve endothelial function. The purpose of this study was to evaluate the effects of weight loss from a high-calcium energy-reduced diet on biomarkers of inflammation, fibrinolysis, and endothelial function in obese individuals. METHODS: In this randomized clinical trial, we analyzed the data from 35 obese adults who lost at least 3% of initial body weight, during a period of 16 wk of energy restriction (-800 Kcal/d). Individuals were randomized into the following dietary regimens: (1) a high calcium diet (HCD; 1200-1300 mg/d) or (2) a low-calcium diet (LCD; <500 mg/d). RESULTS: After 16 wk of intervention subjects on HCD compared with those on LCD exhibited greater reduction in waist circumference and waist-to-hip ratio. Participants on HCD presented a significant reduction in all biomarkers of endothelial dysfunction evaluated in the study (intracellular adhesion molecule-1, vascular cell adhesion molecule 1, and E-Selectin), whereas subjects on LCD showed a significant decrease in intracellular adhesion molecule-1 and E-Selectin. Biomarkers of inflammation and fibrinolysis were reduced in both diets, although without reaching statistical significance. The reduction in all markers of inflammation, fibrinolysis, and endothelial dysfunction was similar in both diets. CONCLUSION: The findings of this study suggest that increased calcium intake during weight loss has no benefits with respect to biomarkers of inflammation, fibrinolysis, and endothelial function.

Consumption of high-polyphenol dark chocolate improves endothelial function in individuals with stage 1 hypertension and excess body weight.

Background. Hypertension and excess body weight are important risk factors for endothelial dysfunction. Recent evidence suggests that high-polyphenol dark chocolate improves endothelial function and lowers blood pressure. This study aimed to evaluate the association of chocolate 70% cocoa intake with metabolic profile, oxidative stress, inflammation, blood pressure, and endothelial function in stage 1 hypertensives with excess body weight. Methods. Intervention clinical trial includes 22 stage 1 hypertensives without previous antihypertensive treatment, aged 18 to 60 years and presents a body mass index between 25.0 and 34.9 kg/m(2). All participants were instructed to consume 50 g of chocolate 70% cocoa/day (2135 mg polyphenols) for 4 weeks. Endothelial function was evaluated by peripheral artery tonometry using Endo-PAT 2000 (Itamar Medical). Results. Twenty participants (10 men) completed the study. Comparison of pre-post intervention revealed that (1) there were no significant changes in anthropometric parameters, percentage body fat, glucose metabolism, lipid profile, biomarkers of inflammation, adhesion molecules, oxidized LDL, and blood pressure; (2) the assessment of endothelial function through the reactive hyperemia index showed a significant increase: 1.94 ± 0.18 to 2.22 ± 0.08, P = 0.01. Conclusion.In individuals with stage 1 hypertension and excess body weight, high-polyphenol dark chocolate improves endothelial function.

Does calcium intake affect cardiovascular risk factors and/or events?

Dietary intervention is an important approach in the prevention of cardiovascular disease. Over the last decade, some studies have suggested that a calcium-rich diet could help to control body weight, with anti-obesity effects. The potential mechanism underlying the impact of calcium on body fat has been investigated, but it is not fully understood. Recent evidence has also suggested that a calcium-rich diet could have beneficial effects on other cardiovascular risk factors, such as insulin resistance, dyslipidemia, hypertension and inflammatory states. In a series of studies, it was observed that a high intake of milk and/or dairy products (the main sources of dietary calcium) is associated with a reduction in the relative risk of cardiovascular disease. However, a few studies suggest that supplemental calcium (mainly calcium carbonate or citrate) may be associated with an increased risk of cardiovascular events. This review will discuss the available evidence regarding the relationship between calcium intake (dietary and supplemental) and different cardiovascular risk factors and/or events.

Association between leptin and its soluble receptor with cardiometabolic risk factors in a Brazilian population.

BACKGROUND: Most studies evaluating the conjoint effects of leptin and human soluble leptin receptor (hs-LR) on cardiometabolic risk factors have been conducted in well-characterized ethnic groups. We aimed to assess the associations of leptin and hs-LR with the cardiometabolic risk factors that reflect the components of metabolic syndrome (MetS) in a Brazilian population with varying degrees of adiposity. METHODS: This is a cross-sectional analysis of adult subjects (n=173, age 45 ± 12 years, 124 women; body mass index [BMI] 35.6 ± 9.5 kg/m(2)) for association of leptin and its soluble receptor with cardiometabolic risk factors (glucose, BMI, waist circumference, hip circumference, blood pressure, insulin, cholesterol and triglycerides). Plasma hs-LR was measured by ELISA; insulin and leptin were determined by RIA. Metabolic syndrome was defined by NCEP/ATP III. RESULTS: Leptin was positively associated with blood pressure, BMI, waist circumference, hip circumference, triglycerides, glucose, insulin and HOMA and inversely correlated with HDL-cholesterol. The hs-LR exhibited inverse relationship with cardiometabolic risk factors (P ≤ 0.006), except for glucose and lipid parameters. Leptin increased, whereas hs-LR decreased, with increasing number of MetS components (P for trend<0.001). In multivariable models, sex, BMI and insulin were independently associated with leptin, whereas age, sex, BMI and systolic blood pressure were the independent correlates of hs-LR. CONCLUSION: In a Brazilian population with complex interethnic admixture, levels of hs-LR and leptin were independently associated with systolic blood pressure and insulin, respectively. Leptin increased with increasing number of MetS components. In turn, hs-LR decreased as the number of MetS components increased.

Does calcium intake affect cardiovascular risk factors and/or events?

Dietary intervention is an important approach in the prevention of cardiovascular disease. Over the last decade, some studies have suggested that a calcium-rich diet could help to control body weight, with anti-obesity effects. The potential mechanism underlying the impact of calcium on body fat has been investigated, but it is not fully understood. Recent evidence has also suggested that a calcium-rich diet could have beneficial effects on other cardiovascular risk factors, such as insulin resistance, dyslipidemia, hypertension and inflammatory states. In a series of studies, it was observed that a high intake of milk and/or dairy products (the main sources of dietary calcium) is associated with a reduction in the relative risk of cardiovascular disease. However, a few studies suggest that supplemental calcium (mainly calcium carbonate or citrate) may be associated with an increased risk of cardiovascular events. This review will discuss the available evidence regarding the relationship between calcium intake (dietary and supplemental) and different cardiovascular risk factors and/or events.

Dietary counseling on long-term weight loss in overweight hypertensive patients.

OBJECTIVE: This study aimed to evaluate long-term weight loss in overweight hypertensive patients receiving dietary counseling. METHODS: Longitudinal study included overweight hypertensive patients who had an initial individual consultation with a nutritionist between January 2002 and December 2005 and were followed for four years in a hypertension clinic. Patients who had at least four consultations during the follow-up period were included in the dietary counseling group. Those who scheduled their first consultation but missed that appointment or had fewer than four consultations during the follow-up period were allocated to the control group. Target Energy intake was calculated at 20-25 kcal/kg actual body weight/day. RESULTS: The study included 102 patients aged 55 ± 1 years old (58 in the dietary counseling group). As compared with the control group, patients in the dietary counseling group showed a significantly greater reduction in body weight (-3.6 ± 0.8 vs. 0.8 ± 0.7 kg), which remained significant after controlling for age, gender, baseline body mass index, and the use of different antihypertensive and antidiabetic drugs. Weight loss between 5.0% and 9.9% was observed in a significantly higher percentage of patients in the dietary counseling group (28% vs. 11%). A weight loss of at least 10% was only observed in dietary counseling group patients, who had a significantly lower odds ratio for increasing the number and/or dosage of antihypertensive agents, even after controlling for age, gender, and baseline body mass index. CONCLUSIONS: Dietary counseling may be associated with long-term weight loss in overweight hypertensive patients.

Dietary calcium intake and its relationship with adiposity and metabolic profile in hypertensive patients.

OBJECTIVE: An inverse relation between dietary calcium and adiposity has been found in several epidemiologic studies. Recent evidence has also suggested that a calcium-rich diet may have beneficial effects on insulin resistance and dyslipidemia. This study aimed to evaluate the association of dietary calcium intake with global adiposity, abdominal obesity, and metabolic profile in hypertensive patients. METHODS: In this cross-sectional study, 85 hypertensive patients 25 to 70 y old underwent clinical, dietary, anthropometric, and biochemical evaluations. Participants were stratified into the following two groups according to their usual dietary calcium intake: low calcium group (<800 mg/d) and high calcium group (≥800 mg/d). RESULTS: Fifty-seven participants (11 men and 46 women) were included in the final analyses. Subjects in the low calcium group compared with those in the high calcium group exhibited significantly higher levels of body mass index and percentage of body fat after adjustments for variables that could interfere with those adiposity parameters (P = 0.03 and 0.01, respectively). Patients in the high calcium group had a lower odds ratio for prevalent obesity than those in the low calcium group, even after controlling for potential confounders (P = 0.01). No significant differences were found in abdominal adiposity and metabolic profile between the two groups. Using data from all patients, an inverse and significant association was observed between dietary calcium intake and percentage of body fat, and it remained after controlling for confounders (P = 0.03). CONCLUSIONS: The findings of the present study suggest that, in hypertensive patients, higher dietary calcium intake could be associated with lower global adiposity.

Dietary counseling on long-term weight loss in overweight hypertensive patients

OBJECTIVE: This study aimed to evaluate long-term weight loss in overweight hypertensive patients receiving dietary counseling. METHODS: Longitudinal study included overweight hypertensive patients who had an initial individual consultation with a nutritionist between January 2002 and December 2005 and were followed for four years in a hypertension clinic. Patients who had at least four consultations during the follow-up period were included in the dietary counseling group. Those who scheduled their first consultation but missed that appointment or had fewer than four consultations during the follow-up period were allocated to the control group. Target Energy intake was calculated at 20-25 kcal/kg actual body weight/day. RESULTS: The study included 102 patients aged 55 + 1 years old (58 in the dietary counseling group). As compared with the control group, patients in the dietary counseling group showed a significantly greater reduction in body weight (-3.6 + 0.8 vs. 0.8 + 0.7 kg), which remained significant after controlling for age, gender, baseline body mass index, and the use of different antihypertensive and antidiabetic drugs. Weight loss between 5.0 percent and 9.9 percent was observed in a significantly higher percentage of patients in the dietary counseling group (28 percent vs. 11 percent). A weight loss of at least 10 percent was only observed in dietary counseling group patients, who had a significantly lower odds ratio for increasing the number and/or dosage of antihypertensive agents, even after controlling for age, gender, and baseline body mass index. CONCLUSIONS: Dietary counseling may be associated with long-term weight loss in overweight hypertensive patients.

Curva-J: conceito, considerações fisiopatológicas e efeito da terapia anti-hipertensiva: [revisão] / J-Curve: concept, pathophysiologic aspects and effects of anti-hypertensivetherapy: [review]

O controle adequado da pressão arterial (PA) traz benefícios incontestáveis em reduzir a mortalidade e a morbidade cardiovascular. Contudo, recentemente, diversas diretrizes vêm preconizando valores cada vez mais baixos não somente para a PA, como também para outros fatores de risco. Contudo, o comportamento dos pacientes hipertensos não tem sido homogêneo. Para o subgrupo de hipertensos com doença arterial coronária (DAC) prévia, vem se observando que a redução dos níveis de pressão arterial diastólica (PAD) abaixo de 80 mmHg traz aumento na ocorrência eventos coronarianos. Por outro lado, não se tem observado o fenômeno da curva J para a pressão arterial sistólica (PAS), tampouco a deterioração da função renal, nem aumento no número de acidentes vasculares cerebrais. Há três prováveis mecanismos propostos para explicar a existência da curva J: 1) a PAD baixa poderia ser um epifenômeno coexistindo ou caracterizando um pobre estado de saúde ou doença crônica (causalidade reversa); 2) a baixa PAD poderia ser causada por um aumento na PA de pulso refletindo doença vascular avançada e rigidez da parede arterial; 3) um agressivo tratamento anti-hipertensivo poderia levar a uma baixa PAD e, assim, à hipoperfusão das coronárias, resultando em eventos coronarianos. Dessa forma, o fenômeno curva J traz duas mensagens clínicas importantes: a primeira é que o médico deve individualizar o melhor tratamento para cada paciente, observando riscos e benefícios para cada intervenção; e a segunda é que esse fato não deve desestimular em perseguir agressivamente um melhor controle da PA, uma vez que menos de um terço dos hipertensos está com a PA controlada.

The rigorous control of arterial blood pressure reduces significantly the morbidity and mortality consequences of arterial hypertension. However, in the presence of coronary artery disease (limited coronary flow reserve) there is aJ-curve relation ship between treated DBP and myocardial infarction, but not for stroke. In such high-risk (ischemic heart disease) cases it would be prudent to avoid lowering DBP to below the low 80s mmHg. Three pathophysiologic mechanisms have been proposed to explain the existence of a J-curve: 1) low DBP could be an epiphenomenon to coexisting or underlying poor health or chronic illness leading to increasing morbidity and mortality (reverse causality); 2)low DBP could be caused by an increased pulse pressure reflecting advanced vascular disease and stiffened large arteries; and 3) over-aggressive antihypertensive treatment could lead to too-low DBP and thus hypoperfusion of the coronaries resulting in coronary events. However, these considerations should not deter practicing physicians from pursuing more aggressive control in treating hypertension, because currently, at best, only approximately one-third o four patients are at goal BPs of < 140/90 mmHg...