Vascular compliance in women with polycystic ovary syndrome treated with spironolactone.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age in the United States and has been associated with several diseases including cardiovascular disease, obesity, and glucose intolerance. In this study, systolic blood pressure, diastolic blood pressure, pulse pressure (vascular compliance), large artery elasticity, systemic vascular resistance (SVR), total vascular impedance (TVI), and body mass index (BMI) were measured before and after treatment with spironolactone in 10 women with PCOS. Systolic BP, diastolic BP, and BMI were similar prior to treatment and after treatment. Pulse pressure decreased slightly post-treatment compared to pretreatment but not to significance (P = 0.07). The results show that after treatment with spironolactone, there was a statistically significant increase in large artery elasticity (P = 0.047), while there was a statistically significant decrease in SVR and TVI (P = 0.0005 and P = 0.03). This study indicates that treatment with spironolactone improves large artery elasticity and reduces systemic vascular resistance without any change in small artery elasticity.

Ambulatory Blood Pressure Monitoring in Lean, Obese and Diabetic Children and Adolescents.

AIM: To determine if children and adolescents who have obesity (Ob) or type 2 diabetes (T2DM) of relatively short duration have impaired cardiovascular function compared with lean subjects using 24-hour ambulatory blood pressure as a surrogate measure of evaluation. METHODS: We enrolled 100 African-Caribbean subjects (45 males/55 females), mean ages 14.4-15.2 years (range 11.8-18.5 years) and Tanner stage 4.2-4.8. Mean BMI for the Ob (n = 40), T2DM (n = 39) and lean (n = 21) groups were 40.3, 34.2 and 20.8, respectively (p < 0.01, Ob and T2DM vs. lean). Mean hemoglobin A1c in lean and Ob was 5.4 and 5.5% compared to 8.8% in T2DM (p < 0.001, T2DM vs. lean and Ob). Ambulatory blood pressure was recorded every 20 min over 24 h using Spacelabs 70207. RESULTS: Mean 24-hour, daytime and nighttime systolic blood pressure was significantly higher in Ob and T2DM compared with lean subjects (mean 24-hour 117 and 120 vs. 109 mm Hg; daytime 121 and 123 vs. 113 mm Hg; and nighttime 109 and 115 vs. 101 mm Hg; p < 0.01 for all time periods). The nocturnal systolic dip in Ob and T2DM did not differ from that of lean, whereas nocturnal diastolic dip decreased significantly in Ob and T2DM compared to lean (11.5 and 10.4 vs. 20.6 mm Hg; p < 0.01). Mean pulse pressure was significantly increased in the Ob and T2DM groups compared to lean subjects (51 and 54 vs. 45 mm Hg; p < 0.01). CONCLUSION: Adolescent Ob and T2DM groups share adverse risk factors, which may be harbingers of adult cardiovascular events.

A Case of Gestational Thyrotoxicosis Associated with Wernicke's Encephalopathy.

OBJECTIVE: To present a case of gestational thyrotoxicosis and hyperemesis gravidarum associated with Wernicke's encephalopathy. METHODS: We present a detailed case report with the clinical, imaging, and laboratory findings of the patient and review the pertinent literature. RESULTS: A 36-year-old woman at 14 weeks of gestation was admitted to the hospital for management of severe hyperemesis gravidarum (HG). While hospitalized, she developed low-grade fever, tachycardia, hypotension, and altered mentation. Laboratory tests were diagnostic of hyperthyroidism. Physical examination revealed a confused, lethargic woman with a normal-size thyroid and pendular nystagmus in primary and lateral gaze. She was treated empirically for thyroid storm with methimazole and other measures. A brain magnetic resonance imaging (MRI) study done later showed hyperintense abnormal signals in bilateral thalamic regions, consistent with Wernicke's encephalopathy (WE). She was immediately started on intravenous thiamine and her mental status improved considerably within 3 to 4 days. Within 2 weeks, the patient's thyroid-function tests normalized and methimazole was discontinued. A repeat brain MRI 6 months later showed marked reduction of signal intensity in both thalamic regions. CONCLUSION: This case demonstrates that gestational thyrotoxicosis in a patient with HG can precipitate acute WE, which may mimic thyroid storm and thus delay appropriate management of this neurologic disorder. We conclude that prophylactic thiamine administration may be considered before caloric replacement in patients who present with HG and acute neurologic dysfunction.

Vascular compliance in lean, obese, and diabetic children and adolescents: a cross-sectional study in a minority population.

BACKGROUND: In adults, both obesity and type 2 diabetes mellitus (T2DM) are positively correlated with cardiovascular disease mortality and arterial stiffness. Several studies of adults have shown that both obesity and T2DM are independently associated with increased arterial stiffness. However, little is known about the relationship between arterial compliance and cardiovascular disease risk in children. We assessed whether large and small arterial compliance is impaired in obese and diabetic pubertal children. METHODS: One hundred children of African-Caribbean ethnicity, aged 14-16 years, including 21 lean children (between the 25th and 75th percentile), 40 obese children (>95th percentile), and 39 children with T2DM diagnosed by American Diabetes Association criteria were studied. Arterial compliance of the large (C1) and small (C2) vessels was measured using radial arterial diastolic pulse wave contour analysis. RESULTS: C1 did not differ significantly between lean, obese, and T2DM subjects. C2 was significantly greater in obese and T2DM subjects (10.9 ± 1 and 10.4 ± 0.7 ml/mm Hg × 100 ml, respectively) compared to lean subjects (7.8 ± 0.8 ml/mm Hg × 100 ml; p < 0.05). C2 was also significantly greater in T2DM subjects receiving antihypertensive drug therapy than in diabetic subjects not on antihypertensive treatment. CONCLUSION: Increased compliance in diabetic and obese children compared to lean subjects could be secondary to premature maturation of the vascular system; whether this early maturation can translate into a subsequent rise in the incidence of cardiovascular events related to diabetes and obesity can only be determined by long-term follow-up of these patients.

Comparative analysis of telmisartan and olmesartan on cardiac function in the transgenic (mRen2)27 rat.

Telmisartan, an angiotensin receptor blocker, may have unique benefits as it possesses partial peroxisome proliferator-activated receptor (PPAR)-γ agonist activity in addition to antihypertensive effects. In this study, we test whether treatment with telmisartan ameliorates cardiovascular abnormalities to a greater extent than olmesartan, which has little PPAR-γ activity. The hypertensive rodent model of tissue renin-angiotensin system activation, transgenic (mRen2)27 (Ren2) rats and their littermate Sprague-Dawley controls were used. Rats were treated with telmisartan (2 mg · kg(-1) · day(-1)), olmesartan (2.5 mg · kg(-1) · day(-1)), or vehicle via drinking water for 3 wk; these doses achieved similar blood pressure control, as measured by telemetry. Ren2 rats displayed impaired diastolic and systolic function using left ventricular (LV) pressure-volume (P-V) analysis. Load-independent diastolic indexes, including the time constant of isovolumic relaxation and the slope of the end-diastolic P-V relationship, as well as systolic indexes, including preload recruitable stroke work, the dP/dt(max)-end-diastolic volume (EDV) relationship, and the P-V area-EDV relationship, were elevated in Ren2 rats compared with Sprague-Dawley controls (P < 0.05). The Ren2 myocardium exhibited parallel increases in the oxidant markers NADPH oxidase and 3-nitrotyrosine. The increase in the prohypertrophic protein Jak2 in Ren2 rats was associated with cardiac structural abnormalities using light microscopic and ultrastructural analysis, which included interstitial fibrosis, cardiomyocyte and LV hypertrophy, and mitochondrial derangements. Both angiotensin receptor blockers attenuate these abnormalities to a similar extent. Our data suggest that the beneficial effect of telmisartan and olmesartan on cardiac structure and function may be predominantly pressor-related or angiotensin type 1 receptor dependent in this model of renin-angiotensin system activation.

Vascular compliance in hypertension: therapeutic implications.

One of three adults and more than 7 of 10 older persons in the United States have hypertension. Of those receiving antihypertensive medication, more than 40% have inadequate blood-pressure control. The predominant subtype of hypertension among older adults is isolated systolic hypertension, which results from stiffening of the wall of the aorta due to various factors, including loss and fragmentation of elastin, increased collagen synthesis, endothelial dysfunction, and higher levels of inflammatory cytokines. Analysis of the peripheral pulse waveform has become widely used as a surrogate marker of central aortic stiffness and a predictor of future cardiovascular disease events. It is a matter of debate whether increased pulse pressure in older adults results primarily from stiffening of the aortic wall and premature reflected pressure waves from peripheral arteries or increased forward pressure waves from a reduced aortic diameter. Anti-stiffening strategies depend on lifestyle changes and pharmacotherapy.

Vascular compliance in the cardiometabolic syndrome.

Elevated systolic blood pressure and increased pulse pressure are important predictors of vascular stiffening (compliance), left ventricular hypertrophy, coronary heart disease, heart failure, stroke, vascular dementia, and chronic kidney disease. Advances in noninvasive methods that measure arterial stiffness have led to increased understanding of the mechanisms underlying vascular dysfunction and the development of associated risk factors. The ability to detect and monitor changes in the physical properties of arteries has the potential to allow early interventions that may prevent disease or attenuate its progression. In this paper, the authors briefly review the various methods available to measure vascular compliance and review pathologic processes that lead to insulin resistance, endothelial dysfunction, inflammation, and sympathetic activation, all of which may contribute to increased arterial stiffness in the cardiometabolic syndrome. Strategies to improve vascular compliance are also discussed.

Vascular compliance in women with polycystic ovary syndrome and healthy women.

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women of reproductive age, has been associated with the cardiometabolic syndrome and increased risk for cardiovascular diseases. Large (C1) and small (C2) vessel compliance and fasting lipids were measured in 45 healthy women and 36 women with PCOS. There were no differences in vacular compliance (C1, C2) between the 2 groups. Systolic blood pressure (116.8 vs 124.3 mm Hg; P=.01), mean arterial pressure (82.5 vs 87 mm Hg; P=.03), and low-density lipoprotein cholesterol (98.1 vs 119 mg/dL; P=.001) were significantly higher in the PCOS group. This difference was not significant after adjusting for age and body mass index. High-density lipoprotein levels in subjects with PCOS were significantly lower than in healthy women (60.2 vs 48.9 mg/dL, P=.02) even after adjusting for age and body mass index. The study indicates that obesity and low high-density lipoprotein are the major contributing factors to cardiovascular changes in PCOS.

Diabetes and arterial stiffening.

Type 2 diabetes (DM-2) has become a major global health problem that has been fueled mainly by increasing obesity and aging of the population. Most studies show that arterial stiffening occurs across all age groups in both type 1 diabetes and DM-2, and among those with impaired fasting glucose, impaired glucose tolerance, and the metabolic syndrome. Arterial stiffening in DM-2 results, in part, from the clustering of hyperglycemia, dyslipidemia and hypertension, all of which may promote insulin resistance, oxidative stress, endothelial dysfunction, and the formation of pro-inflammatory cytokines and advanced glycosylation end-products. Likewise, aging may increase arterial stiffening by altering the proportions of elastin and collagen in the aorta. The consequences of arterial stiffening are increased pulse pressure, hypertension, and a greater risk of cardiovascular disease. Treatment strategies to reduce or prevent arterial stiffening include pharmacologic agents that block the renin-angiotensin-aldosterone system, relax vascular smooth muscle, enhance release of nitric oxide from endothelial cells, and break glycosylation end-product cross-links, and fish oil supplementation.

Adrenocortical hypertension.

Primary aldosteronism, congenital adrenal hyperplasia, Cushing's syndrome, glucocorticoid-remediable aldosteronism, and corticotropin-dependent forms of adrenal pathology can cause hypertension by excessive production of adrenocortical hormones. Although traditional biochemical assays continue to be used, genetic testing has simplified the diagnosis of glucocorticoid-remediable aldosteronism. Also new interventional radiologic approaches for the diagnosis and treatment of corticotropin-dependent forms of Cushing's syndrome are available. Medical and surgical approaches, however, still remain viable options for treatment.

High-fat meal impairs vascular compliance in a subgroup of young healthy subjects.

Postprandial hypertriglyceridemia impairs endothelial function and may possibly worsen vascular compliance by increasing oxidative stress. Large (C1) and small (C2) artery compliance, glucose, insulin, and triglycerides (TGs) were measured hourly for 6 hours in 18 young healthy volunteers after a low-fat meal and a high-fat meal, with and without antioxidant vitamins. C1 and C2 declined significantly for 6 hours after fat ingestion in 8 subjects ("fat reactors") and increased in 10 ("nonreactors"). Fat reactors had higher fasting and peak serum TGs after fat loading and increased baseline glucose and insulin levels and homeostasis model assessment of insulin resistance (HOMA(IR)). Fasting insulin correlated with C1 and C2 only in fat reactors. After fat intake, plasma nitric oxide metabolites decreased more in fat reactors than in nonreactors (17.0% +/- 5.1% vs 4.8% +/- 2.1%; P < .05). In fat reactors, pretreatment with antioxidant vitamins before the high-fat meal blunted the fall in C1 but not in C2. Compliance was unchanged after the low-fat meal. Normal weight young subjects with an insulin resistance phenotype show significantly decreased vascular compliance, increased postprandial TG peaks, and markedly reduced plasma nitric oxide metabolites after a high-fat meal.

Effect of fixed-dose ACE-inhibitor/calcium channel blocker combination therapy vs. ACE-inhibitor monotherapy on arterial compliance in hypertensive patients with type 2 diabetes.

Assessment of vascular compliance may be a useful measurement of the clinical effects of antihypertensive treatment. Both angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers are known to improve vascular elasticity. A study was performed to test the hypothesis that combined therapy with an ACE inhibitor and a calcium channel blocker would have additive benefits on vascular compliance at similar levels of blood pressure (BP), as compared with monotherapy with an ACE inhibitor. This 12-week, double-blind study was a substudy of a larger clinical hypertension study conducted in patients with hypertension and type 2 diabetes. Subjects (N = 20) were randomized to either a fixed-dose combination of amlodipine besylate/benazepril HCl or to enalapril monotherapy. BP, heart rate, large- and small-vessel compliance, systemic vascular resistance, and urinary microalbumin excretion were assessed at baseline and after treatment. Both treatments were similarly effective in lowering BP, reducing systemic vascular resistance, and decreasing urinary microalbumin excretion. Improvement in large-vessel compliance was significantly greater among subjects who received ACE-inhibitor/calcium channel blocker combination therapy (52%) as compared with those who received ACE-inhibitor monotherapy (32%; p < 0.05). No significant change in small-vessel compliance was observed with either treatment. Greater improvement in large-vessel compliance with combination therapy was independent of BP lowering.

The Effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may attenuate the efficacy of antihypertensive agents in high-risk patients. Therefore, we conducted a double-blind, randomized trial to evaluate the effects of celecoxib, rofecoxib, and naproxen on 24-hour blood pressure (BP) in patients with type 2 diabetes, hypertension, and osteoarthritis. METHODS: Patients were randomly assigned to treatment with 200 mg of celecoxib once daily (n = 136), 25 mg of rofecoxib once daily (n = 138), or 500 mg of naproxen twice daily (n = 130) for 12 weeks. Twenty-four-hour ambulatory BP monitoring and validated arthritis efficacy assessments were conducted at randomization and at weeks 6 and 12 of treatment. The primary end point was the mean change from baseline in average 24-hour systolic BP at week 6. RESULTS: Reductions in osteoarthritis symptoms, including pain, mobility, and stiffness, were similar in all treatment groups. The mean +/- SE 24-hour systolic BP following 6 weeks of therapy was increased significantly by rofecoxib (from 130.3 +/- 1.2 to 134.5 +/- 1.4 mm Hg; P < .001) but not by celecoxib (132.0 +/- 1.3 to 131.9 +/- 1.3 mm Hg; P = .54) or naproxen (133.7 +/- 1.5 to 133.0 +/- 1.4 mm Hg; P = .74). The BP difference between rofecoxib and celecoxib was 3.78 mm Hg (95% confidence interval, 1.18-6.38; P = .005); between rofecoxib and naproxen, 3.85 mm Hg (95% confidence interval, 1.15-6.55; P = .005). The proportion of patients with controlled hypertension at baseline who developed ambulatory hypertension by week 6 (24-hour systolic BP>135 mm Hg) was significantly greater with rofecoxib (30%) than with celecoxib (16%) (P = .05) but not significantly greater than with naproxen (19%). CONCLUSIONS: At equally effective doses for osteoarthritis management, treatment with rofecoxib but not celecoxib or naproxen induced a significant increase in 24-hour systolic BP. However, destabilization of hypertension control occurred to some extent in all 3 treatment groups; this phenomenon was seen more often in patients treated with rofecoxib than with the other therapies.

Adrenocortical hypertension.

Primary aldosteronism, congenital adrenal hyperplasia, Cushing's syndrome, glucocorticoid-remediable aldosteronism, and corticotropin-dependent forms of adrenal pathology can cause hypertension by excessive production of adrenocortical hormones. Although traditional biochemical assays continue to be used, genetic testing has simplified the diagnosis of glucocorticoid-remediable aldosteronism. Also, new interventional radiologic approaches for the diagnosis and treatment of corticotropin-dependent forms of Cushing's syndrome are available. Medical and surgical approaches, however, still remain viable options for treatment.

Epidemiology of diabetes.

The incidence of diabetes mellitus, particularly type 2 diabetes, is increasing dramatically in the United States and in other Westernized, industrialized societies because of increasing obesity, sedentary lifestyle, and population aging. There are currently 20 million persons with diabetes in the United States, of whom more than 5 million remain undiagnosed. The diabetic population consumes a disproportionate share of health care resources because of both microvascular and macrovascular complications. Diabetes is a major cause of new-onset blindness, end-stage renal disease, and nontraumatic amputation in the United States. Cardiovascular disease accounts for up to 80% of premature excess mortality in diabetic patients. Strategies to lessen the disease burden in these patients include hygienic measures (diet and exercise) as well as rigorous treatment of hypertension, dyslipidemia, and hyperglycemia.

Role of the natriuretic peptide system in cardiorenal protection.

Significant progress has been made in the understanding of the neurohormonal factors that contribute to the progression of chronic renal and cardiac failure and the development of target-organ damage in patients with hypertension and diabetes. We herein review some of these advances, including a new therapeutic strategy for potentially enhancing cardiorenal protection in patients with these disorders.

Vascular compliance in diabetes.

The measurement of vascular compliance has assumed increasing importance as a powerful predictor of cardiovascular and all-cause mortality. Arterial stiffness increases with the duration of diabetes, older age, and concomitant hypertension. Hyperglycemia may increase arterial stiffness in diabetes by reducing the bioactivity of endothelium-derived nitric oxide (NO) either by decreasing NO production or inactivating NO by interaction with oxygen-derived free radicals. New approaches to therapy, such as the use of advanced glycation end product "breakers," may potentially benefit patients with diabetes.

Control of cardiovascular risk factors in patients with diabetes and hypertension at urban academic medical centers.

OBJECTIVE: There are national mandates to reduce blood pressure (BP) to <130/85 mmHg, LDL cholesterol to <100 mg/dl, and HbA(1c) to <7% and to institute aspirin therapy in patients with diabetes. The objective of this study was to determine the proportion of patients in urban institutions with diabetes and hypertension who meet these treatment goals. RESEARCH DESIGN AND METHODS: Using American Diabetes Association (ADA) guidelines, we evaluated the control of cardiovascular disease (CVD) risk factors in 1,372 patients receiving medical care at two major urban medical centers in Brooklyn and Detroit. Information was extracted from charts of outpatient clinics. RESULTS: Of 1,372 active clinic patients with diabetes and hypertension, 1,247 (90.9%) had type 2 diabetes, and 26.7% met the target blood pressure of 130/85 mmHg. A total of 35.5% met the goal LDL cholesterol level of <100 mg/dl, 26.7% had an HbA(1c) <7%, and 45.6% were on antiplatelet therapy. Only 3.2% of patients met the combined ADA goal for BP, LDL cholesterol, and HbA(1c). CONCLUSIONS: Optimal control of CVD risk factors in adults with diabetes was achieved only in a minority of patients. Results reflect the inherent difficulties in achieving these complex guidelines in our present health care systems.

The use of ACE inhibitors on diabetic patients without renal disease.

Strategies that interrupt the renin-angiotensin system, especially with angiotensin-converting enzyme (ACE) inhibition, reduce cardiovascular disease mortality and morbidity in high-risk persons such as those with the insulin resistance syndrome and diabetes mellitus. In the 1980s emphasis was placed on the renal protective effects of ACE inhibitors in patients with diabetes and proteinuria. During the past several years controlled clinical trials have demonstrated that ACE inhibition reduces cardiovascular disease (CVD) mortality and morbidity. This is especially important in patients in the United States, where 80% of excess mortality for diabetes mellitus is attributed to CVD. This article reviews the clinical trials in high-risk patients, especially those with diabetes, that shown beneficial CVD risk reduction with ACE inhibitors.