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March 2010

Current options for the treatment of resistant hypertension.

Patients with resistant hypertension are those who have uncontrolled blood pressure despite use of three or more antihypertensive medications, or those who require four or more medications to achieve control. When evaluating resistant hypertension it is important to rule out pseudoresistant hypertension that may result from factors including poor blood pressure measurement technique and the white coat effect. Potential contributing factors should be identified and reversed if possible, including obesity, excess alcohol intake and use of interfering medications such as NSAIDS, sympathomimetics and oral contraceptives. Modification of lifestyle factors such as weight loss, sodium restriction and physical activity is paramount for treatment success. Secondary causes of hypertension are common in this patient group and, therefore, appropriate screening tests should be carried out as necessary. Pharmacologic therapy is centered on combination therapy of medications from different mechanisms of action, especially diuretics, which are essential in maximizing antihypertensive effects. The role of mineralocorticoid antagonists is expanding, especially in patients with obstructive sleep apnea and obesity where aldosterone excess may be implicated. Finally, when appropriate, specialist referral may facilitate blood pressure reduction and the ability to meet target blood pressure goals.

Expert Rev Cardiovasc Ther. 2009 Nov;7(11):1385-93.

Effect of antihypertensive therapy on serum lipids in newly diagnosed essential hypertensive men.

The effect of antihypertensives on serum lipids in newly diagnosed male essential hypertensive patients was studied. The participants (n = 99) were randomly allocated to receive amlodipine, atenolol, enalapril, hydrochlorothiazide, and a combination of amlodipine and atenolol. Lipid parameters were estimated before and after 8 weeks of therapy. The atenolol and thiazide group showed a significant increase in triglycerides (TGs) and very-low-density lipoprotein cholesterol (VLDL-C). High-density lipoprotein cholesterol (HDL-C) and HDL-C to low-density lipoprotein cholesterol (LDL-C) ratio were significantly increased and TC to HDL-C ratio was significantly decreased in the amlodipine and amlodipine- atenolol combination groups. In the enalapril group, we found a significant reduction in TC, TGs, VLDL-C, non-HDL-C, and TG to HDL-C ratio after treatment. It can be concluded from the present study that some drugs have beneficial effects on the lipid status, whereas others adversely affect the lipid status in hypertension.

Angiology. 2009 Apr-May;60(2):217-20.

The prediabetic problem: development of non-insulin-dependent diabetes mellitus and related abnormalities.

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with approximately two fold increase in coronary heart disease (CHD) in men and fourfold increase in CHD in women. In most studies, the duration of diabetes and severity of glycemia are only weakly related to CHD in NIDDM, suggesting that the prediabetic period may be important for the increased CHD in NIDDM subjects. Both hyperinsulinemia and/or insulin resistance predict the development of NIDDM. A number of studies have shown that increased cardiovascular risk factors (especially high triglyceride, blood pressure, and small dense low-density lipoprotein (LDL) and low high-density liproprotein (HDL) cholesterol) precede the onset of NIDDM. Recent data from the San Antonio Heart Study suggest that the atherogenic pattern of cardiovascular risk factors is more marked in prediabetic women than in prediabetic men, thus partially explaining the higher risk of CHD in prediabetic women than in prediabetic men. The atherogenic changes in cardiovascular risk factors appear to be mainly due to increased hyperinsulinemia and insulin resistance in nondiabetic subjects. Interventions to reduce cardiovascular disease in NIDDM subjects should emphasize the primary prevention of NIDDM and very aggressive treatment of traditional cardiovascular risk factors in prediabetic subjects. Treatment of hypertension and dyslipidemia in high-risk patients for NIDDM should avoid agents that further worsen insulin resistance (nicotinic acid, beta blockers, and thiazides), as subjects with hypertension and dyslipidemia are already at increased risk of NIDDM.

J Diabetes Complications. 1997 Mar-Apr;11(2):69-76.

Metabolic and clinical outcomes in nondiabetic individuals with the metabolic syndrome assigned to chlorthalidone, amlodipine, or lisinopril as initial treatment for hypertension: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

OBJECTIVE: Optimal initial antihypertensive drug therapy in people with the metabolic syndrome is unknown. RESEARCH DESIGN AND METHODS: We conducted a subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) to compare metabolic, cardiovascular, and renal outcomes in individuals assigned to initial hypertension treatment with a thiazide-like diuretic (chlorthalidone), a calcium channel blocker (CCB; amlodipine), or an ACE inhibitor (lisinopril) in nondiabetic individuals with or without metabolic syndrome. RESULTS: In participants with metabolic syndrome, at 4 years of follow-up, the incidence of newly diagnosed diabetes (fasting glucose >or=126 mg/dl) was 17.1% for chlorthalidone, 16.0% for amlodipine (P = 0.49, chlorthalidone vs. amlodipine) and 12.6% for lisinopril (P < 0.05, lisinopril vs. chlorthalidone). For those without metabolic syndrome, the rate of newly diagnosed diabetes was 7.7% for chlorthalidone, 4.2% for amlodipine, and 4.7% for lisinopril (P < 0.05 for both comparisons). There were no differences in relative risks (RRs) for outcomes with amlodipine compared with chlorthalidone in those with metabolic syndrome; in those without metabolic syndrome, there was a higher risk for heart failure (RR 1.55 [95% CI 1.25-1.35]). In comparison with lisinopril, chlorthalidone was superior in those with metabolic syndrome with respect to heart failure (1.31 [1.04-1.64]) and combined cardiovascular disease (CVD) (1.19 [1.07-1.32]). No significant treatment group-metabolic syndrome interaction was noted. CONCLUSIONS: Despite a less favorable metabolic profile, thiazide-like diuretic initial therapy for hypertension offers similar, and in some instances possibly superior, CVD outcomes in older hypertensive adults with metabolic syndrome, as compared with treatment with CCBs and ACE inhibitors.

Diabetes Care. 2008 Feb;31(2):353-60.

Types of dietary fat and risk of coronary heart disease: a critical review.

During the past several decades, reduction in fat intake has been the main focus of national dietary recommendations to decrease risk of coronary heart disease (CHD). Several lines of evidence. however, have indicated that types of fat have a more important role in determining risk of CHD than total amount of fat in the diet. Metabolic studies have long established that the type of fat, but not total amount of fat, predicts serum cholesterol levels. In addition, results from epidemiologic studies and controlled clinical trials have indicated that replacing saturated fat with unsaturated fat is more effective in lowering risk of CHD than simply reducing total fat consumption. Moreover, prospective cohort studies and secondary prevention trials have provided strong evidence that an increasing intake of n-3 fatty acids from fish or plant sources substantially lowers risk of cardiovascular mortality. In this article, we review evidence from epidemiologic studies and dietary intervention trials addressing the relationship between dietary fat intake and risk of CHD, with a particular emphasis on different major types of fat, n-3 fatty acids and the optimal balance between n-3 and n-6 fatty acids. We also discuss the implications of the available evidence in the context of current dietary recommendations.

J Am Coll Nutr. 2001 Feb;20(1):5-19.

Fructose, weight gain, and the insulin resistance syndrome.

This review explores whether fructose consumption might be a contributing factor to the development of obesity and the accompanying metabolic abnormalities observed in the insulin resistance syndrome. The per capita disappearance data for fructose from the combined consumption of sucrose and high-fructose corn syrup have increased by 26%, from 64 g/d in 1970 to 81 g/d in 1997. Both plasma insulin and leptin act in the central nervous system in the long-term regulation of energy homeostasis. Because fructose does not stimulate insulin secretion from pancreatic beta cells, the consumption of foods and beverages containing fructose produces smaller postprandial insulin excursions than does consumption of glucose-containing carbohydrate. Because leptin production is regulated by insulin responses to meals, fructose consumption also reduces circulating leptin concentrations. The combined effects of lowered circulating leptin and insulin in individuals who consume diets that are high in dietary fructose could therefore increase the likelihood of weight gain and its associated metabolic sequelae. In addition, fructose, compared with glucose, is preferentially metabolized to lipid in the liver. Fructose consumption induces insulin resistance, impaired glucose tolerance, hyperinsulinemia, hypertriacylglycerolemia, and hypertension in animal models. The data in humans are less clear. Although there are existing data on the metabolic and endocrine effects of dietary fructose that suggest that increased consumption of fructose may be detrimental in terms of body weight and adiposity and the metabolic indexes associated with the insulin resistance syndrome, much more research is needed to fully understand the metabolic effect of dietary fructose in humans.

Am J Clin Nutr. 2002 Nov;76(5):911-22.

Body composition and dietary intakes in adult celiac disease patients consuming a strict gluten-free diet.

BACKGROUND: Celiac disease responds to dietary gluten withdrawal, but data on the long-term effects of gluten-free diets are discordant. OBJECTIVE: Our aim was to evaluate the nutritional status and body composition of adult celiac disease patients consuming a gluten-free diet who were in clinical, biochemical, and histologic remission. DESIGN: We studied 71 patients (51 women and 20 men; mean age: 27 y; range: 17-58 y) and 142 healthy control subjects matched by sex and age. The subjects’ height, weight, body mass index, fat and lean mass, and bone mineral content (evaluated by dual-energy X-ray absorptiometry) were measured; a 3-d dietary questionnaire was administered; and total daily energy, fat, carbohydrate, and protein intakes were calculated. RESULTS: The weight, height, and body mass index of male celiac disease patients and the weight and body mass index of female celiac disease patients were significantly lower than the corresponding measurements in control subjects. The fat and lean mass of both male and female patients was significantly different from that of control subjects; however, bone mineral content was significantly lower only in females in whom celiac disease was diagnosed in adulthood. Total energy intake was lower in the patients than in the control subjects (9,686 +/- 1,569 and 11,297 +/- 1318 kJ/d in males and 6,736 +/- 1,318 and 7,740 +/- 1,715 kJ/d in females), and the diet of the patients was unbalanced, with a higher percentage of energy as fat and a lower percentage of energy as carbohydrates. CONCLUSIONS: Although strictly compliant with their gluten-free diet and in complete remission, patients with celiac disease showed differences in body composition and dietary intakes compared with control subjects. Strict follow-up and dietary advice in terms of the choice and composition of foods seem necessary to prevent malnutrition.

Am J Clin Nutr. 2000 Oct;72(4):937-9.

Increased serum high-density lipoprotein-cholesterol concentration in celiac disease after gluten-free diet treatment correlates with body fat stores.

BACKGROUND: Low high-density lipoprotein-cholesterol (HDL-C) concentration correlates with increased cardiovascular risk. A great prevalence of celiac disease (CD) was reported among patients with low HDL-C concentration, and gluten-free diet (GFD) treatment seems to normalize lipid profile. We evaluated blood lipids and body composition in 26 CD patients with low HDL-C level (<1.0 mmol/L) at diagnosis and after GFD. STUDY: A case-control study. METHODS: The diagnosis was based on histologic evidence of subtotal or total duodenal villous atrophy. Patients were studied before and after GFD treatment (14.2+/-1.4 mo) with biopsy-proven return to normal of the duodenal mucosa. HDL-C was enzymatically assessed after precipitation of very low-density lipoprotein and low-density lipoprotein with heparin-magnesium. Apolipoprotein (Apo)-AI level was assessed by immunoturbidimetric assay; triglycerides by an enzymatic colorimetric method. Body composition was assessed by dual-energy x-ray absorptiometry. RESULTS: Body composition improved after GFD, with increasing body weight (P<0.05) essentially owing to increased fat mass (FM) (P<0.01), rather than fat-free mass (P=0.064). Total cholesterol and HDL-C were lower in untreated compared with treated patients (P<0.001 and P<0.0001). Apo-AI level increased significantly after GFD (1.20+/-0.22 vs. 1.46+/-0.17 g/L; P<0.0001). Apo-AI, sex, and FM were all significant determinants of HDL-C level; a positive correlation (R=0.68; P<0.0001) was found between increase in HDL-C level and in FM after GFD treatment. CONCLUSIONS: Restoration of lipid profile in CD patients after GFD treatment may be explained by an increase in both Apo-AI secretion by intestinal cells and body fat stores.

J Clin Gastroenterol. 2009 Nov-Dec;43(10):946-9.