Marion R. Wofford

HYPERTENSION AND ANTIHYPERTENSIVE THERAPY AS RISK FACTORS FOR TYPE 2 DIABETES MELLITUS

BACKGROUND Previous research has suggested that thiazide diuretics and beta-blockers may promote the development of type 2 diabetes mellitus. However, the results of previous studies have been inconsistent, and many studies have been limited by inadequate data on outcomes and by potential confounding. METHODS We conducted a prospective study of 12,550 adults 45 to 64 years old who did not have diabetes. An extensive health evaluation conducted at base line included assessment of medication use and measurement of blood pressure with a random-zero sphygmomanometer. The incidence of new cases of diabetes was assessed after three years and after six years by measurement of serum glucose concentrations while the subjects were fasting. RESULTS After simultaneous adjustment for age, sex, race, education, adiposity, family history with respect to diabetes, physical-activity level, other health-related behavior, and coexisting illnesses, subjects with hypertension who were taking thiazide diuretics were not at greater risk for the subsequent development of diabetes than were subjects with hypertension who were not receiving any antihypertensive therapy (relative hazard, 0.91; 95 percent confidence interval, 0.73 to 1.13). Likewise, subjects who were taking angiotensin-converting-enzyme inhibitors and calcium-channel antagonists were not at greater risk than those not taking any medication. In contrast, subjects with hypertension who were taking beta-blockers had a 28 percent higher risk of subsequent diabetes (relative hazard, 1.28; 95 percent confidence interval, 1.04 to 1.57). CONCLUSIONS Concern about the risk of diabetes should not discourage physicians from prescribing thiazide diuretics to nondiabetic adults who have hypertension. The use of beta-blockers appears to increase the risk of diabetes, but this adverse effect must be weighed against the proven benefits of beta-blockers in reducing the risk of cardiovascular events.

Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study

BACKGROUND Retinal microvascular abnormalities reflect damage from hypertension and other vascular processes. We examined the relation of such abnormalities to incident stroke. METHODS A cohort of 10358 men and women (aged 51 to 72 years) living in four US communities underwent retinal photography and standard grading for retinal microvascular abnormalities. The calibres of all retinal arterioles and venules were measured after digital conversion of the photographs, and a summary arteriole-to-venule ratio (AVR) was calculated as an index of arteriolar narrowing (smaller AVR indicates greater narrowing). Cases of incident stroke admitted to hospital were identified and validated by case record reviews. FINDINGS Over an average of 3.5 years, 110 participants had incident strokes. After adjustment for age, sex, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, most retinal microvascular characteristics were predictive of incident stroke, with adjusted relative risks of 2.58 (1.59-4.20) for any retinopathy, 3.11 (1.71-5.65) for microaneurysms, 3.08 (1.42-6.68) for soft exudates, 2.55 (1.27-5.14) for blot haemorrhages, 2.26 (1.00-5.12) for flame-shaped haemorrhages, and 1.60 (1.03-2.47) for arteriovenous nicking. The relative risk of stroke increased with decreasing AVR (p=0.03). The associations were similar for ischaemic strokes specifically, and for strokes in individuals with hypertension, either with or without diabetes. INTERPRETATION Retinal microvascular abnormalities are related to incident stroke. The findings support a microvascular role in the pathogenesis of stroke. They suggest that retinal photography may be useful for cerebrovascular-risk stratification in appropriate populations.

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.

Antihypertensive effect of α- and β-adrenergic blockade in obese and lean hypertensive subjects

The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients. Thirteen obese, hypertensive patients with a body mass index (BMI) ≥28 kg/m2 (obese) and nine lean patients with a BMI ≤25 kg/m2 (lean) were recruited. After a 1-week washout period, participants underwent daytime ambulatory blood pressure monitoring (ABPM). Participants were then treated with the α-adrenergic antagonist doxazosin, titrating to 4 mg QHS in 1 week. In the next week, the β-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week. One month after the addition of atenolol, all patients underwent a second ABPM session. There were no differences between the obese and lean subjects in baseline systolic (SBP), diastolic (DBP), or mean arterial pressures (MAP) measured by office recording or ABPM. However, obese subjects had higher heart rates than lean subjects (87.5 ± 2.4 v 76.8 ± 4.9 beats/min). After 1 month of treatment with the adrenergic blockers, obese patients had a significantly lower SBP (130.0 ± 2.5 v 138.9 ± 2.1 mm Hg, P = .02) and MAP (99.6 ± 2.3 v 107.0 ± 1.5 mm Hg, P = .02) than lean patients. Obese patients also tended to have a lower DBP than lean patients (84.3 ± 2.5 v 90.9 ± 1.6 mm Hg, P = .057), but there was no significant difference in heart rate after 1 month of adrenergic blockade. These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity.

Pathophysiology and treatment of obesity hypertension.

Excess weight gain accounts for as much as 65-75% of the risk for essential hypertension and also greatly increases the risk for end stage renal disease (ESRD). Obesity raises blood pressure by increasing renal tubular reabsorption, impairing pressure natriuresis, and causing volume expansion due to activation of the sympathetic nervous system (SNS) and renin-angiotensin aldosterone system (RAAS), and by physical compression of the kidneys, especially when visceral obesity is present. The mechanisms of SNS activation in obesity are still unclear but may be due, in part, to hyperleptinemia that stimulates the hypothalamic pro-opiomelanocortin (POMC) pathway. With prolonged obesity, there may be a gradual loss of kidney function that worsens with time, exacerbates hypertension, and makes blood pressure more difficult to control. Lifestyle modifications, including weight reduction and increased physical activity, are essential first steps in the management of obesity hypertension and renal disease. Anti-obesity drugs offer potential pharmacotherapy for obesity hypertension, but current drugs are very limited and additional long-term studies are needed to test their safety and efficacy. Clinical trials are also needed to determine the most effective antihypertensive drugs for obese hypertensive patients. Special considerations for the obese patient, in addition to adequately controlling the blood pressure, include correcting the metabolic abnormalities and protecting the kidneys from further injury.

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.

Cognitive Impairment Associated with Atorvastatin and Simvastatin

Clinical guidelines for cholesterol testing and management have been updated recently. With the evolving recognition of benefits and intensified recommendations for cholesterol management, many more patients will require cholesterol‐lowering drugs. All the statins share similar adverse‐effect profiles, with a low overall frequency of undesirable effects. Emerging data associate statins with a decreased risk of Alzheimers disease; however, we report two women who experienced significant cognitive impairment temporally related to statin therapy. One woman took atorvastatin, and the other first took atorvastatin, then was rechallenged with simvastatin. Clinicians should be aware of cognitive impairment and dementia as potential adverse effects associated with statin therapy.

Hypertension in Postmenopausal Women

Blood pressure is typically lower in premenopausal women than in men. However, after menopause, the prevalence of hypertension in women is higher than it is in men. Hypertension is a major risk factor for cardiovascular disease in women and men, but cardiovascular disease is the leading cause of death in women. Furthermore, there is evidence that blood pressure may not be as well-controlled in women as in men, despite the fact that most women adhere better to their therapeutic regimens and medications than do men, and have their blood pressures measured more frequently than do men. This review describes possible mechanisms by which blood pressure may be increased in postmenopausal women.

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.

Effect of Dietary Protein Supplementation on Blood Pressure

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.