Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial.

Introduction. The purpose of this trial was to evaluate the effect of pterostilbene on metabolic parameters. Methods. A prospective, randomized, double-blind, and placebo-controlled study that enrolled 80 patients with a total cholesterol ≥200 mg/dL and/or LDL ≥ 100 mg/dL. Subjects were divided into four groups: (1) pterostilbene 125 mg twice daily; (2) pterostilbene 50 mg twice daily; (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily; (4) matching placebo twice daily for 6-8 weeks. Endpoints included lipids, blood pressure, and weight. Linear mixed models were used to examine and compare changes in parameters over time. Models were adjusted for age, gender, and race. Results. LDL increased with pterostilbene monotherapy (17.1 mg/dL; P = 0.001) which was not seen with GE combination (P = 0.47). Presence of a baseline cholesterol medication appeared to attenuate LDL effects. Both systolic (-7.8 mmHg; P < 0.01) and diastolic blood pressure (-7.3 mmHg; P < 0.001) were reduced with high dose pterostilbene. Patients not on cholesterol medication (n = 51) exhibited minor weight loss with pterostilbene (-0.62 kg/m(2); P = 0.012). Conclusion. Pterostilbene increases LDL and reduces blood pressure in adults. This trial is registered with Clinicaltrials.gov NCT01267227.

Resistant nonalcoholic fatty liver disease amelioration with rosuvastatin and pioglitazone combination therapy in a patient with metabolic syndrome.

OBJECTIVE: To report a case describing resolution of persistently elevated aminotransferases in a patient with severe, resistant nonalcoholic fatty liver disease (NAFLD) using combination therapy. CASE SUMMARY: A 47-year-old obese male patient presented with a history of elevated aminotransferases and numerous statin intolerances. In addition to worsening control of diabetes and dyslipidemia, severe NAFLD was confirmed. Rosuvastatin was started, which induced short-term elevations in aminotransferases resulting in patient discontinuation. Biochemical markers of NAFLD worsened over time. Therefore, both rosuvastatin 20 mg daily and pioglitazone 15 mg daily were started simultaneously to potentially blunt the early increase in transaminases seen with rosuvastatin. At 2 weeks, the patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had decreased 57% and 56% from baseline, respectively. By 9 months, the patient's ALT and AST serum concentrations had normalized. Repeat liver ultrasound demonstrated improvement in steatosis grading and reduction in liver size. These improvements occurred despite a 4.5-kg weight gain since starting rosuvastatin and pioglitazone. DISCUSSION: Pharmacotherapy in NAFLD is not well validated, particularly combination therapy. Medications that target obesity-related consequences are commonly used, although evidence regarding biochemical and histological improvement is inconclusive. Consideration should be given to the use of combination of thiazolidinediones and statins for rapid biochemical improvement and long-term histological impact. CONCLUSIONS: The improvement in this patient's biochemical and ultrasonographic markers of resistant, severe NAFLD was rapid and sustained with combination therapy. This case represents a potential solution for initiating or maintaining statin therapy in patients with NAFLD who are at high cardiovascular risk.

Analysis of safety from a human clinical trial with pterostilbene.

Objectives. The purpose of this trial was to evaluate the safety of long-term pterostilbene administration in humans. Methodology. The trial was a prospective, randomized, double-blind placebo-controlled intervention trial enrolling patients with hypercholesterolemia (defined as a baseline total cholesterol ≥200 mg/dL and/or baseline low-density lipoprotein cholesterol ≥100 mg/dL). Eighty subjects were divided equally into one of four groups: (1) pterostilbene 125 mg twice daily, (2) pterostilbene 50 mg twice daily, (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily, and (4) matching placebo twice daily for 6-8 weeks. Safety markers included biochemical and subjective measures. Linear mixed models were used to estimate primary safety measure treatment effects. Results. The majority of patients completed the trial (91.3%). The average age was 54 years. The majority of patients were females (71%) and Caucasians (70%). There were no adverse drug reactions (ADRs) on hepatic, renal, or glucose markers based on biochemical analysis. There were no statistically significant self-reported or major ADRs. Conclusion. Pterostilbene is generally safe for use in humans up to 250 mg/day.

Pharmacologic therapy for nonalcoholic fatty liver disease in adults.

Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in hepatocytes in the absence of excessive alcohol intake, ranging in severity from simple steatosis to nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis can ultimately progress to cirrhosis and hepatocellular carcinoma. NAFLD is associated with cardiometabolic risk factors and is the most common chronic liver disease among adults in the Western Hemisphere. Although simple steatosis is generally considered a self-limiting disease, evidence suggests an increased risk of cardiovascular disease, and, less conclusively, mortality, among individuals with NAFLD and/or NASH. The current standard of care for the treatment of patients with NAFLD focuses on lifestyle interventions, particularly diet and exercise. There is a lack of consensus regarding the most effective and appropriate pharmacologic therapy. A PubMed search was conducted using the medical subject heading terms "fatty liver" and "steatohepatitis." This review focuses on the current pharmacologic options available for treating adults with NAFLD and/or NASH. Continued investigation of drugs or combinations that improve NAFLD progression is crucial. Clinicians, particularly pharmacists, must take an active role in identification and appropriate selection of pharmacotherapy for NAFLD.

Evaluation of blood pressure measurement and agreement in an academic health sciences center.

The authors assessed the process of blood pressure (BP) measurement and level of adherence to recommended procedures at representative sites throughout a large academic health sciences center. A casual observer assessed the setting and observed the process, noting the equipment, technique, and BP recorded by site personnel. A trained observer then repeated the patient's BP measurement following American Heart Association recommendations. Significant biases were observed between measurements by site personnel and the trained observer. Site personnel reported on average an increased systolic BP (SBP) of 5.66 mm Hg (95% confidence interval [CI], 3.09-8.23; P<.001) and a decreased diastolic BP (DBP) of -2.96 mm Hg (95% CI, -5.05 to -0.87; P=.005). Overall, 41% of patients had a ≥10-mm Hg difference in SBP between measurements. Similarly, 54% had differences of ≥5 mm Hg in DBP between measurements. Inaccurate BP measurement and poor technique may lead to misclassification, misdiagnosis, and inappropriate medical decisions. Concordance of measured SBP between our site personnel and trained observer was less than optimal. Several areas for improvement were identified. Routine calibration and use of system-wide standardized equipment, establishment of BP measurement protocols, and periodic technique and equipment recertification can be addressed in future quality initiatives.

Effect of dietary protein supplementation on blood pressure: a randomized, controlled trial.

BACKGROUND: Observational studies have reported an inverse association between dietary protein intake and blood pressure (BP). We compared the effect of soy protein, milk protein, and carbohydrate supplementation on BP among healthy adults. METHODS AND RESULTS: We conducted a randomized, double-blind crossover trial with 3 intervention phases among 352 adults with prehypertension or stage 1 hypertension in New Orleans, LA, and Jackson, MS, from September 2003 to April 2008. The trial participants were assigned to take 40 g/d soy protein, milk protein, or carbohydrate supplementation each for 8 weeks in a random order. A 3-week washout period was implemented between the interventions. Three BPs were measured at 2 baseline and 2 termination visits during each of 3 intervention phases with a random-zero sphygmomanometer. Compared with carbohydrate controls, soy protein and milk protein supplementations were significantly associated with -2.0 mm Hg (95% confidence interval -3.2 to -0.7 mm Hg, P=0.002) and -2.3 mm Hg (-3.7 to -1.0 mm Hg, P=0.0007) net changes in systolic BP, respectively. Diastolic BP was also reduced, but this change did not reach statistical significance. There was no significant difference in the BP reductions achieved between soy or milk protein supplementation. CONCLUSIONS: The results from this randomized, controlled trial indicate that both soy and milk protein intake reduce systolic BP compared with a high-glycemic-index refined carbohydrate among patients with prehypertension and stage 1 hypertension. Furthermore, these findings suggest that partially replacing carbohydrate with soy or milk protein might be an important component of nutrition intervention strategies for the prevention and treatment of hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00107744.

Socioeconomic position is positively associated with blood pressure dipping among African-American adults: the Jackson Heart Study.

BACKGROUND: Blunted nocturnal blood pressure (NBP) dipping is a significant predictor of cardiovascular events. Lower socioeconomic position (SEP) may be an important predictor of NBP dipping, especially in African Americans (AA). However, the determinants of NBP dipping are not fully understood. METHODS: The cross-sectional associations of individual and neighborhood SEP with NBP dipping, assessed by 24-h ambulatory BP monitoring, were examined among 837 AA adults (Mean age: 59.2 ± 10.7 years; 69.2% women), after adjustment for age, sex, hypertension status, body mass index (BMI), health behaviors, office, and 24-h systolic BP (SBP). RESULTS: The mean hourly SBP was consistently lower among participants in the highest category of individual income compared to those in the lowest category, and these differences were most pronounced during sleeping hours. The odds of NBP dipping (defined as >10% decline in the mean asleep SBP compared to the mean awake SBP) increased by 31% (95% confidence interval: 13-53%) and 18% (95% confidence interval: 0-39%) for each s.d. increase in income and years of education, respectively, after multivariable adjustment. CONCLUSIONS: NBP dipping is patterned by income and education in AA adults even after accounting for known risk factors. These results suggest that low SEP is a risk factor for insufficient NBP dipping in AA.

Improving influenza vaccination rates by targeting individuals not seeking early seasonal vaccination.

BACKGROUND: Influenza morbidity and mortality remain high in the United States although vaccination clearly improves health outcomes and reduces health expenditures. This study was designed to assess the effectiveness of mail and telephone reminder strategies on improving existing clinic influenza vaccination rates among those not seeking early seasonal vaccination. METHODS: In mid-November, we randomized 1371 patients at a hypertension clinic into 1 of 2 intervention groups, a mail reminder group (letter plus the Centers for Disease Control [CDC] Influenza Vaccine Information Statement) or a phone reminder group (same information via a personal phone call), or a control group. The following spring, records were reviewed for vaccination documentation. Patients without documentation were contacted by phone to identify whether vaccination for the current season had been obtained. RESULTS: The final analysis included 884 patients (62% women, mean age 57.2 years old): 325 in the mail reminder group, 246 in the phone reminder group, and 313 represented the control group. Overall, 388 of these patients (44%) were vaccinated. Vaccination rates were significantly higher in the intervention groups, 46% for the mail reminder group (age and sex adjusted odds ratio [OR], 1.8, 95% confidence interval [CI], 1.3-2.5; P=.001) and 56% for the phone reminder group (OR, 2.8; 95% CI, 1.9-4.0; P<.0001), compared to 33% in the control group. Both interventions increased vaccination rates in all age/sex groups. CONCLUSION: In contrast to earlier studies, this intervention occurred later in the influenza vaccination period excluding those who seek early vaccination and allowing interventions to target those less likely to receive vaccination. Compared to previous studies demonstrating only trivial or modest benefits, both mail and phone reminders effectively increased clinic vaccination rates in our group of patients.

Hypertension: issues in control and resistance.

Hypertension remains uncontrolled in more than 50% of treated patients. Barriers to hypertension control include those that are patient-related, physician-related, and related to the health system. Identification of uncontrolled hypertension, pseudoresistant hyper-tension, and resistant hypertension require thoughtful attention to accurate blood pressure measurement, lifestyle factors, evaluation for secondary causes of hypertension, and proper treatment. Recent guidelines emphasize the importance of aggressive treatment and referral to hypertension specialists for patients with resistant hypertension, defined as blood pressure that remains above goal despite the use of three appropriate anti-hypertensive agents.

The treatment of hypertension in obese patients.

Hypertension causes a significant disease burden in all racial and ethnic groups and is directly attributable to excess weight in most cases. The relationship between increasing body mass index and hypertension prevalence has been recognized for decades. Epidemiologic studies clearly demonstrate the correlation between body weight and blood pressure in obese and lean populations. Most patients with hypertension are overweight or obese, and loss of excess weight lowers blood pressure. Although the epidemiologic relationship is clear, the understanding of mechanisms linking hypertension and weight gain is still evolving. Lifestyle modifications and specific pharmacologic agents address many of the known mechanisms; however, blood pressure remains difficult to control in obese hypertensive patients. This review highlights the association of obesity and hypertension, identifies potential mechanisms for this association, and describes nonpharmacologic and pharmacologic strategies that offer potential benefits for the obese patient with hypertension.

Racial and ethnic differences in hypertension.

Hypertension is a major cause of disease burden in all racial and ethnic groups and in both developing and developed regions and countries. Much of the racial and ethnic disparity in cardiovascular outcomes can be attributed to the excess burden of hypertension. Racial and ethnic differences in blood pressure occur because of biology and sociology. Causes of racial differences in blood pressure likely begin early in life and reflect the complex relationship of these gene and environment interactions. Hypertension treatment and control remain less than optimal worldwide, and awareness is still a problem in many racial and ethnic groups. Instituting lifestyle changes for the primary prevention and treatment of hypertension among the general population would decrease prevalence and be effective in eliminating many racial and ethnic differences. This review highlights racial and ethnic differences in the prevalence and incidence of hypertension and identifies contributing factors associated with these differences.

Prevalence, awareness, treatment, and control of hypertension in the Jackson Heart Study.

African Americans have higher reported hypertension prevalence and lower control rates than other ethnic groups in the United States. Hypertension prevalence, awareness, treatment, and control (outcomes) and potentially associated demographic, lifestyle, comorbidity, and health care access factors were examined in 5249 adult participants (3362 women and 1887 men) aged 21 to 94 years enrolled in the Jackson Heart Study. Hypertension prevalence (62.9%), awareness (87.3%), treatment (83.2%), and control (66.4%) were high. Control declined with advancing age; estimates for all of the outcomes were higher for women compared with men. Lower socioeconomic status was associated with prevalence and control. Smoking was negatively associated with awareness and treatment, particularly among men. Comorbidities (diabetes, chronic kidney disease, and cardiovascular disease), likely driven by the high rates of obesity, correlated with hypertension prevalence, awareness, treatment, and control. Lack of health insurance was marginally associated with poorer control, whereas use of preventive care was positively associated with prevalence, awareness, and treatment, particularly among men. In comparisons with the 1994-2004 National Health and Nutrition Examination Survey data adjusted to Jackson Heart Study sex, age, and socioeconomic status distribution, control rates among Jackson Heart Study participants appeared to be higher than in their national counterparts and similar to that of whites. These results suggest that public health efforts to increase awareness and treatment among African Americans have been relatively effective. The Jackson Heart Study data indicate that better control rates can be achieved in this high-risk population.

A Katrina experience: lessons learned.

PURPOSE: Almost no data exist on how best to respond to the medical needs of civilians displaced by natural disasters. After Hurricane Katrina destroyed the Gulf Coast and seriously damaged the infrastructure of Jackson, Miss, the University of Mississippi Medical Center (UMMC) was challenged with serving a large group of evacuees at a major Red Cross evacuation shelter near our campus. We reviewed our experiences and share lessons learned. METHODS: This is a retrospective review of administrative and clinical records for patients served by a medical clinic established emergently after Hurricane Katrina. RESULTS: Red Cross regulations precluded their volunteers from providing medical care other than first aid. Faced with numerous evacuees seeking medical assistance, UMMC established an ambulatory clinic at the shelter. The majority of patients had multiple medical problems, no medical insurance, and limited ability to purchase medications. The greatest need was for management of chronic illnesses. The clinic provided 2394 patient visits and filled more than 4902 prescriptions over 17 days. CONCLUSION: While medical facilities have emergency response plans for epidemics and mass trauma, little attention has focused on plans for care of evacuated populations. Shelter operators should consider advance coordination of medical care with existing health care systems. Medical facilities along evacuation routes should be aware that they may be asked to provide care for sheltered evacuees.

Serum uric acid predicts incident hypertension in a biethnic cohort: the atherosclerosis risk in communities study.

Serum uric acid has been positively associated with incident hypertension, but previous studies have had limited ability to explore this relationship across sex and ethnic strata. We sought to evaluate this association in a biethnic cohort of middle-aged men and women. Participants in the Atherosclerosis Risk in Communities (ARIC) study who were free of hypertension at baseline (N=9104) were evaluated for hypertension at 3-year intervals over 4 examinations. Adjusted Cox proportional hazards models evaluated risk of incident hypertension or progression of blood category for each SD higher baseline serum uric acid. At baseline, the mean age was 53.3 years (range: 45 to 64 years), with a mean (SD) systolic blood pressure of 113.8 (12.2) mm Hg, mean diastolic blood pressure of 70.2 (8.6) mm Hg, and mean serum uric acid of 5.7 (1.4). Higher serum uric acid was associated with greater risk of hypertension in the overall cohort (hazard ratio for each SD of higher uric acid [95% CI]: 1.10 [1.04 to 1.15]) and in subgroup analyses (black men: 1.32 [1.14 to 1.54]; black women: 1.16 [1.03 to 1.31]; white men: 1.01 [0.94 to 1.09]; white women: 1.04 [0.96 to 1.11]), after adjustment for age, baseline blood pressure, body mass index, renal function, diabetes, and smoking. The pattern was similar when modeling blood pressure progression (overall: 1.10 [1.05 to 1.14]; black men: 1.26 [1.11 to 1.42]; black women: 1.18 [1.06 to 1.31]; white men: 1.05 [0.99 to 1.11]; white women: 1.05 [1.00 to 1.12]). In conclusion, serum uric acid was positively associated with incident hypertension over 9 years of follow-up, and this relationship was stronger in blacks than in whites. More research is warranted concerning the physiological and clinical consequences of hyperuricemia, especially in blacks.

Drug-induced metabolic syndrome.

The metabolic syndrome is a cluster of risk factors associated with an increased risk for cardiovascular disease and type 2 diabetes. Based on data from 1988 to 1994, it is estimated that 24% of adults in the United States meet the criteria for diagnosis of the metabolic syndrome. The use of certain medications may increase the risk of the metabolic syndrome by either promoting weight gain or altering lipid or glucose metabolism. Health providers should recognize and understand the risk associated with certain medications and appropriately monitor for changes related to the metabolic syndrome. Careful attention to drug choices should be paid in patients who are overweight or have other risk factors for diabetes or cardiovascular disease.

Exercise, insulin resistance, and hypertension: a complex relationship.

More than 300,000 deaths occur annually in the United States alone as a result of obesity, poor dietary habits, or physical inactivity. Obesity is now an increasingly recognized independent risk factor for cardiovascular disease and leads to numerous other comorbidities. The causal relationships between obesity and both insulin resistance and hypertension have been consistently demonstrated in numerous studies. The relationships consist of cascading events involving insulin, leptin, adiponectin, and other hormones that often precipitate the development of metabolic syndrome. As we learn more about the metabolic activity of the adipose tissue, we can better identify the mechanisms that associate weight reduction with a decrease in health risks. Evidence suggests that exercise produces a positive effect on weight reduction, insulin sensitivity, and blood pressure. Therefore, weight reduction and therapeutic changes in lifestyle should be encouraged in all overweight and obese patients. It is imperative to increase the awareness of the obesity epidemic and to emphasize the importance of exercise as both treatment and prevention of metabolic disease.