Does masked hypertension exist in healthy volunteers and apparently well-controlled hypertensive patients?

BACKGROUND: Home blood pressure (HB P) measurement is considered to reflect BP during the day better than office BP (OB P). But in some patients HB P is higher than OB P. This is called masked hypertension (MH). OBJECTIVE: To examine whether MH occurs in healthy volunteers and apparently well-controlled hypertensives. METHODS: 57 treated hypertensive patients and 31 healthy volunteers (27/22 men) participated. Mean age (+/- SD ) was 61 +/- 13 and 29 +/- 13 years, respectively. Patients were instructed to measure their BP twice daily for three days (3 readings each) with the Omron 705 CP device after at least 10 minutes rest in a comfortable sitting position. In the outpatient department, OB P was measured four times, in duplicate, every ten minutes by the physician using the same device and under similar conditions. RESULTS: Mean HB P of the treated hypertensive group was 146/84 +/- 18/10 mmHg, significantly higher than OB P 136/79 +/- 19/10 (p.     

Do beta-blockers prevent coronary events in hypertensive patients?

Beta-blockers have been considered for decades as effective agents in preventing coronary events in hypertensive patients. Actually, the scrutiny of the available data arises some doubts over the real value of this pharmacological class. In primary prevention, the clinical benefits of beta-blockers are poorly documented: the studies conducted against placebo (MRC, IPPPSH...) did not show any significant differences regarding the rate of coronary events (except within non smokers); moreover, the beneficial effect of propranolol in preventing sudden deaths and silent myocardial infarctions has been reported byjust one retrospective analysis. Likewise in HAPPHY study, the comparison with diuretics did not emphasize a clear superiority of one of both classes; the better effect of metoprolol regarding overall mortality and fatal coronary events was shown in the pecular subset MAPHY, only. Furthermore, in elderly people, HEP, MRC OA and STOP studies did not find any significant effect of beta-blockers in preventing coronary events, as compared with placebo. However, SHEP study, which involved patients older than 60 years with isolated systolic hypertension receiving first a diuretic, then a beta-blocker(atenolol) in 1/4 of the cases, demonstrated a significant reduction versus placebo both in strokes and in coronary events. Finally, in UKPDS, CAPP, LIFE and CONVINCE studies, atenolol turned out to have a similar efficacy as captopril, losartan and verapamil, in preventing ischemic heart disease. Among the numerous published meta-analyses, that of Psaty pointed out the absence of a primary cardioprotective effect by beta-blockers; more recently, that of Carlberg, emphasized atenolol given alone as the first-line drug to fail in significantly reducing coronary events and strokes. In secondary prevention, some more convincing data may be found in the literature, regarding post myocardial infarction patients (meta-analyses of Staessen, 1982, Yusuf, 1985 and Soriano, 1997), as well as those with stable angina (BIP study in diabetics) or silent ischemia (ASIST study: significant reduction in number and duration of ischemic events by atenolol). Moreover, INVEST study recently showed atenolol and verapamil to have an equivalent efficacy in the hypertensive patients with stable coronary artery disease. Last, hypertension should be reminded as resulting in many cases of heart failure, a pathology where beta-blockers have clearly demonstrated their beneficial effects.     

Does carvedilol impair insulin sensitivity in heart failure patients without diabetes?

BACKGROUND: An increased risk for impaired glucose tolerance or diabetes was shown in patients on beta-blockers, whereas alpha1 blockers seem to have favorable effects on glycemic profile. In this study, the metabolic effect of carvedilol in nondiabetic patients with chronic heart failure (CHF) was evaluated. METHODS AND RESULTS: Twenty-eight nondiabetic CHF patients were enrolled. Before being started on carvedilol and on the highest tolerated dose, each patient underwent an oral glucose tolerance test and fasting insulin, glycohemoglobin, lipid concentrations were measured and insulin sensitivity indices (HOMA, ISI-gly, and ISI-composite) were calculated. An impaired glucose tolerance was found (2-hour glycemia 144 +/- 42 mg/dL), with a fasting glycemia at upper limits of normal (108 +/- 13 mg/dL) and no significant differences between basal and carvedilol treatment measurements. Fasting insulinemia significantly decreased during carvedilol treatment (13.6 +/- 7.3 versus 9.8 +/- 5.1 muU/mL; P = .022), with a reduction of the HOMA index (3.75 +/- 1.95 versus 2.73 +/- 1.47; P = 034) and an increase of the ISI-gly index (0.85 +/- 0.22 versus 1.03 +/- 0.31; P = .025). The lipoprotein profile did not significantly change. CONCLUSION: Carvedilol might have some positive metabolic effects on increasing insulin sensitivity that would make it suitable for diabetic patients that have a worse prognosis than non diabetic patients with CHF.     

Adipocytokines mark insulin sensitivity in euthyroid Hashimoto’s patients

The relationship between inflammation, Hashimoto’s thyroiditis (HT) and insulin resistance is still controversial. In this regard, a pretty complete evaluation of adipocytokines levels in patients with HT has not been performed so far. We assessed retinol binding protein-4 (RBP4), adipocyte-fatty acid binding protein (A-FABP), neutrophil gelatinase–associated lipocalin (NGAL) and tumor necrosis factor-α (TNFα) levels in 93 euthyroid HT patients and 51 healthy controls (CTL), also evaluating the possible correlation between adipocytokines levels and markers of insulin resistance. No significant differences between HT patients and CTL in fasting plasma glucose and insulin levels, and HOMA index were observed. HT patients had significantly higher RBP4, NGAL and A-FABP levels than CTL, while TNFα levels did not differ between the two groups. In HT patients, RBP4 was significantly related with fT3 and fT4 levels, while A-FABP with fT4 only. Moreover, in HT patients, either RBP4 or A-FABP was directly associated with plasma insulin and HOMA index. Circulating levels of these adipocytokines were not influenced by the presence of antithyroid peroxidase or antithyroglobulin autoantibodies or only one of them, neither by autoantibodies titer. In conclusion, euthyroid HT patients are characterized by a peculiar inflammatory response of the adipose tissue, apparently related to an early reduction in insulin sensitivity and to serum thyroid hormone levels, although within the normal range. These results suggest that HT patients with high RBP4 and A-FABP levels might deserve a particular attention, being potentially more exposed to develop insulin resistance and increased cardiovascular risk.     

Adipocyte insulin binding and insulin sensitivity in ‘brittle’ diabetes

Summary Adipocyte insulin binding and insulin sensitivity to stimulation of lipogenesis were assessed in a group of extremely brittle diabetic patients who were resistant to subcutaneous insulin therapy and had required frequent and prolonged hospital admission. These patients had significantly lower maximum adipocyte insulin binding (1.78±0.18%) than age-, sex- and weight-matched stable diabetic control subjects (2.57±0.36%; p<0.05). Scatchard analysis suggested that the decreased binding was secondary to reduced receptor affinity with no change in receptor number. Adipocytes from the brittle subjects displayed resistance to insulin stimulation of lipogenesis compared with those from diabetic or normal control groups (half-maximal stimulation at 34±4, 15±3 and 13±2 pmol/l respectively; p<0.01 between brittle and stable diabetic groups). In the one subject who was treated with intraperitoneal insulin, the changes in insulin binding and sensitivity were found to have reverted towards normal. The peripheral tissue abnormalities of brittle diabetes may exacerbate the clinical syndrome although the relationship of these changes to the primary cause of the syndrome is uncertain.     

Do we need to target 'prediabetic' hypertensive patients?

Patients at risk for diabetes development have been recently characterized as those presenting higher baseline serum glucose concentration, increased body mass index, elevated systolic blood pressure, reduced serum high-density lipoprotein-cholesterol and those with history of prior use of antihypertensive drugs. Little is known, however, about the long-term outcome of patients at high risk for diabetes development, so-called 'prediabetic' patients. Prediabetes state has been defined as the presence of either impaired glucose tolerance or impaired fasting glucose, and accumulating evidence suggests that individuals with a non-diabetic range of hyperglycaemia (prediabetic) are already at risk for cardiovascular diseases. This short review analyses the need of targeting 'prediabetic' hypertensive patients in order to develop strategies for cardiovascular protection intended to diminish the consequences of precipitating the development of diabetes and its cardiovascular and renal deleterious effects.     

Is the nocturnal fall in blood pressure reduced in essential hypertensive patients with metabolic syndrome?

OBJECTIVE: The aim of this study was to examine whether an impaired reduction in nocturnal blood pressure (BP), defined on the basis of two periods of ambulatory BP monitoring (ABPM), is present in hypertensive patients with metabolic syndrome, as defined by the NCEP criteria. METHODS: 460 grade 1 and 2 untreated essential hypertensives (mean age 45.9 +/- 11.9 years) referred for the first time to our outpatient hospital clinic underwent the following procedures: 1) medical history and physical examination; 2) repeated clinic BP measurements; 3) routine examinations; 4) ABPM over two 24-hour periods within 4 weeks. Metabolic syndrome was defined as at least three of the following alterations: increased waist circumference, increased triglycerides, decreased HDL-cholesterol, increased BP, or high fasting glucose. Nocturnal dipping was defined as a night-time reduction in average SBP and DBP >10% compared to average daytime values. RESULTS: The 135 patients with metabolic syndrome (group I) were similar for age, gender and known duration of hypertension to the 325 patients without it (group II). There were no significant differences between the two groups in average 48-hour, daytime, night-time SBP/DBP values and the percentage nocturnal SBP and DBP decrease (-17.7 / -15.7 vs. -18.4 / -16.2, p = ns). A reproducible nocturnal dipping (decrease in BP >10% from mean daytime in both ABPM periods) and non-dipping profile (decrease in BP < or =10% in both ABPM periods) was found in 74 (54.8%) and 29 (21.4%) in group I and in 169 (52.1%) and 73 (22.4%) in group II, respectively (p = ns); 32 patients (23.7%) in group I and 83 patients (25.5%) in group II had a variable dipping profile (p = ns). CONCLUSIONS: This study shows that no significant difference exists in nocturnal BP patterns, assessed by two ABPMs, in untreated essential hypertensive patients with metabolic syndrome compared to those without it.     

Advanced emphysema in African-American and white patients: do differences exist?

BACKGROUND: Emphysema is the only smoking-related disease in which white patients have higher prevalence and higher attributable mortality rates than African-American patients. Epidemiologic studies have not addressed, nor explained, the observed racial differences in emphysema. STUDY OBJECTIVES: To determine whether white and African-American patients differ with respect to the magnitude, anatomic distribution, and physiologic impairments of emphysema. PATIENTS: Characteristics of patients with severe and very severe emphysema enrolled in the National Emphysema Treatment Trial were examined and compared. Patient demographics, cardiopulmonary function, quality of life, and severity/distribution of the emphysema by quantitative CT were analyzed. RESULTS: Of the 1,218 patients enrolled in the trial, 42 were African American (3.4%) and 1,156 were white (95%). African Americans were younger (mean age +/- SD, 63 +/- 7 years vs 67 +/- 6 years) and smoked less (26 +/- 14 cigarettes per day vs 32 +/- 14 cigarettes per day) than white patients (p = 0.01). There was no difference between the two racial groups in pulmonary function (FEV1, 27 +/- 6% predicted vs 27 +/- 7% predicted), gas exchange (Pa(O2), 66 +/- 11 mm Hg vs 65 +/- 10 mm Hg), and exercise (33 +/- 14 W vs 36 +/- 21 W), respectively. Quality of life measures were similar between the groups, but African Americans had a lower socioeconomic status, lower education level, and fewer were married. Radiographic analysis of the extent of emphysema in African Americans, who were matched with selected white patients, revealed significantly less emphysema in the former group and different distribution of severe emphysema. CONCLUSIONS: African Americans with emphysema were younger and had a similar degree of lung impairment as the white study population despite smoking less. In a subgroup of matched patients, the severity and distribution of emphysema by quantitative radiographic analysis were different.     

Do antihypertensive drugs really have antitumor effects? Baseline differences in hypertensive and non-hypertensive patients with advanced pancreatic cancer

Although the antitumor effects of antihypertensive drugs for patients with advanced pancreatic cancer (APC) have been investigated, their efficacy remains unclear. Previous studies suggest that hypertensive (HT) patients with APC are significantly older than non-HT patients with APC, and that other major baseline differences in patient characteristics which may affect prognosis exist between HT and non-HT patients. It is also possible that antihypertensive drugs lack antitumor activity. Therefore, we herein retrospectively investigated the baseline differences between HT and non-HT patients with APC. From January 2015 to April 2020, 56 patients with APC received nab-paclitaxel plus gemcitabine as first-line chemotherapy at Higashiosaka City Medical Center (Higashiosaka, Japan). Of these 56 patients, 30 were diagnosed with hypertension (HT group); the remaining 26 did not have hypertension (non-HT group). Differences between the two groups were compared and prognostic factors were evaluated. Patients in the HT group had significantly less sarcopenia, a significantly larger body mass index, were significantly older, and significantly more likely to have a regular doctor and primary site in the body and tail of the pancreas than those in the non-HT group. Although no significant difference was found in the treatment response, patients in the HT group were significantly more likely to move to second-line chemotherapy than those in the non-HT group. Survival curves showed that median overall survival (OS) in the HT group was significantly longer (10.5 months) than in the non-HT group (6.8 months, P = .04). Multivariate analysis did not identify the use of antihypertensive drugs as an independent prognostic factor of OS. We identified key baseline differences in the characteristics of APC patients with and without HT, suggesting that major selection bias could occur when investigating the efficacy of antihypertensive drugs in all populations. Therefore, it is possible that antihypertensive drugs lack antitumor activity. To determine the true efficacy of antihypertensive drugs for APC, HT, and non-HT patients in another population should be investigated, or a prospective, randomized, controlled trial conducted that is stratified by HT or non-HT status.     

Systemic inflammation and insulin sensitivity in obese IFN-γ knockout mice

Adipose tissue macrophages are important mediators of inflammation and insulin resistance in obesity. IFN-γ is a central regulator of macrophage function. The role of IFN-γ in regulating systemic inflammation and insulin resistance in obesity is unknown. We studied obese IFN-γ knockout mice to identify the role of IFN-γ in regulating inflammation and insulin sensitivity in obesity. IFN-γ-knockout C57Bl/6 mice and wild-type control litter mates were maintained on normal chow or a high fat diet for 13 weeks and then underwent insulin sensitivity testing then sacrifice and tissue collection. Flow cytometry, intracellular cytokine staining, and QRTPCR were used to define tissue lymphocyte phenotype and cytokine expression profiles. Adipocyte size was determined from whole adipose tissue explants examined under immunofluorescence microscopy. Diet-induced obesity induced systemic inflammation and insulin resistance, along with a pan-leukocyte adipose tissue infiltrate that includes macrophages, T-cells, and NK cells. Obese IFN-γ-knockout animals, compared with obese wild-type control animals, demonstrate modest improvements in insulin sensitivity, decreased adipocyte size, and an M2-shift in ATM phenotype and cytokine expression. These data suggest a role for IFN-γ in the regulation of inflammation and glucose homeostasis in obesity though multiple potential mechanisms, including effects on adipogenesis, cytokine expression, and macrophage phenotype.     

Anxiety and depression in various functional gastrointestinal disorders: Do differences exist?

OBJECTIVE: To examine the differences in the prevalence and severity of anxiety and depression in patients with functional dyspepsia (FD), nonerosive reflux disease (NERD), irritable bowel syndrome (IBS) and healthy controls. METHODS: Consecutive patients undergoing an index endoscopic examination for various symptoms were interviewed. All the three functional gastrointestinal disorders (FGIDs) were diagnosed according to the Rome III criteria. Anxiety and depression were diagnosed using a locally validated version of the hospital anxiety and depression scale. RESULTS: A total of 248 patients were recruited (62 in FD, NERD, IBS and control groups each) with no differences in the basic characteristics. There was a higher prevalence of anxiety and depression in FD, NERD and IBS groups than that in the control group (43.5%, 45.2% and 67.7% vs 14.5%, P < 0.001; and 22.6%, 33.9% and 38.7% vs 6.5%, P < 0.0001). Using the cut‐off score (> 8) for anxiety or depression, IBS patients had a higher rate of anxiety than FD (P = 0.01) and NERD (P = 0.02), while no significant differences in depression rates were observed among all three groups. CONLUSION: Anxiety is more common in patients with IBS than in those with FD and NERD, indicating a possible causal link in the former.     

Does rational therapy exist in patients with Crohn's disease and ulcerative colitis?

Crohn's disease and ulcerative colitis belong to an autoimmune mediated, civilizing diseases having a rise of incidence. The cause of both disease is still unknown with undoubted importance of diet, a lifestyle and using ofantimicrobial drugs in the last fifty years. The rational therapy is based to use the drugs with high anti-inflammatory efficacy. The choice of therapy is driven due to disease course in individual patient. The integral part of patients follow up are activities directing to minimize of drug's side effects.     

Are ethnic differences in insulin sensitivity explained by variation in carbohydrate intake?

Aims/hypothesis Minority populations are disproportionately affected by diabetes. This health disparity may be due to less healthy diets and/or heritable factors in minority populations. These factors must be assessed concurrently to better appreciate their contribution to insulin sensitivity.Methods We analysed overweight, healthy adults using the National Health and Nutrition Examination Survey 1999–2000. Means for dietary intake variables and insulin sensitivity were calculated by ethnicity. Linear regressions were performed to evaluate the association between ethnicity, dietary variables, dietary glycaemic index and insulin sensitivity. Fasting insulin was used to characterise insulin sensitivity.Results Non-Hispanic whites have higher energy and fat intake, while Hispanics have higher carbohydrate intake and African-Americans have lower fibre intake. In unadjusted analyses both Hispanics and African-Americans have lower insulin sensitivity, but only Hispanics are more likely to have lower insulin sensitivity after controlling for dietary variables and BMI.Conclusions/interpretation Ethnic differences in insulin sensitivity remain after controlling for dietary differences and other factors, suggesting that inherent metabolic differences exist. Further studies are needed to define inherent metabolic factors, as well as other non-dietary factors that affect insulin sensitivity.