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Thomas D Giles

Publications and source records attributed to Thomas D Giles.

At least 19 recordsLinked to original sources

Should we redefine hypertension?

In the past, hypertension has been defined as a systemic arterial blood pressure chronically exceeding certain levels. However, it is now apparent that there is no blood pressure threshold that separates those with increased cardiovascular risk from those with no or low risk. Hypertension is a complex disease that eventually leads to an increase in blood pressure above optimal values for an individual. Moreover, levels of blood pressure, a physical force, need to be evaluated in the context of other cardiovascular risk factors. This definition of hypertension will permit physicians to treat patients with the goal of reducing global risk for myocardial infarction, stroke, and chronic kidney disease.

Antihypertensive Agents↗

Circadian rhythm of blood pressure and the relation to cardiovascular events.

Incidences of potentially life-threatening cardiovascular events display a diurnal pattern, tending to be higher in the morning than at other times of day. The recording of blood pressure at pre-defined intervals under everyday circumstances is facilitated by ambulatory blood pressure monitoring (ABPM). This technique shows that systolic and diastolic blood pressures display a circadian rhythm in most individuals. Typically, at the end of the night on arousal, blood pressure surges. This surge coincides with increased cardiovascular events. A recent prospective study conducted in Japan, where the incidence of stroke is high, provides further evidence for the link between cardiovascular events and morning blood pressure surge. Prevalence of both silent ischaemic events and multiple cerebrovascular infarcts was highest among the elderly subjects studied, with the largest increase in blood pressure on awakening. An increased risk of cardiovascular morbidity and mortality is also seen in 'non-dippers' (i.e. individuals in whom the normal nocturnal fall in blood pressure is absent or blunted). ABPM is superior to clinic blood pressure in predicting cardiovascular morbidity and mortality, and this suggests that 24-h blood pressure control may be necessary to gain complete benefit from blood pressure-lowering therapy. Antihypertensive agents with a long duration of action have the potential to provide blood pressure control throughout the dosing interval and thus cover the critical early morning period when the blood pressure surges. Clinical studies that have compared telmisartan with shorter-acting angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors demonstrate that telmisartan has a sustained duration of action, with proven efficacy over the entire 24-h period between doses, including the critical early morning period.

Angiotensin II Type 1 Receptor Blockers↗

An effectiveness study comparing algorithm-based antihypertensive therapy with previous treatments using conventional and ambulatory blood pressure measurements.

Effectiveness trials in hypertension enable the efficacy and safety of new drugs to be compared with previous therapy. Since these open-label trials could inadvertently be influenced by observer bias, this study has used ambulatory blood pressure monitoring (ABPM) to provide a rigorous blinded end point to validate the study conclusions. The study was performed in 675 patients with stage 1 or 2 hypertension despite receiving single-agent or fixed-dose combination therapy. After baseline ABPM, the previous treatment was replaced by telmisartan 40 mg daily; if control (office blood pressure <140/90 mm Hg) was not achieved in 2 weeks, the dose was increased to 80 mg, and if necessary, a fixed combination with hydrochlorothiazide 12.5 mg was used after a further 4 weeks. ABPM was repeated after 4 weeks on final therapy. Overall, 50% of patients finished on monotherapy and 50% on combination therapy. By office measurements, there was a decrease (mean +/- SEM) of 16.8+/-0.5/10.3+/-0.3 mm Hg (p<0.001) when telmisartan-based treatment replaced previous treatment; by ABPM, the decrease was 8.2+/-0.4/5.0+/-0.2 mm Hg (p<0.001). The decreases were significant for comparisons with each of the prior drug classes. A treatment algorithm based on the angiotensin receptor blocker, telmisartan, was confirmed by the blinded end point of ABPM as an efficacious alternative to other antihypertensive regimens in clinical practice.

Aged↗

Atherosclerotic renal artery stenosis and renovascular hypertension: clinical diagnosis and indications for revascularization.

Atherosclerotic renal artery stenosis (RAS) is relatively common and often associated with reversible hypertension, progressive renal insufficiency, and/or coronary-independent pulmonary edema. Not all RAS is associated with renovascular hypertension. Historical and physical findings may suggest renovascular hypertension and warrant investigation for RAS. Noninvasive diagnostic imaging options include renal artery duplex ultrasonography, magnetic resonance angiography, computed tomographic angiography, and CO2 angiography, with each method having its own advantages and limitations. Functional tests of renal flow, which characterize RAS significance, include captopril-stimulated plasma renin activity and captopril renography. To date, no single approach has shown clear superiority either in diagnosis or identification of patients most likely to benefit from revascularization. Revascularization of RAS is recommended for severe/drug-refractory hypertension, preservation of renal function, recurrent flash pulmonary edema, or recurrent severe heart failure. Intervention response is variable, but the ongoing Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, comparing medical therapy with and without stenting, should provide management guidance.

Angiography↗

Assessment of global risk: a foundation for a new, better definition of hypertension.

The prevalence of individuals with increased blood pressure (BP) is growing. A greater understanding of the various pathogenetic mechanisms of hypertension and associated BP increases would provide a better strategy for preventing and treating this condition. Hypertension is strongly associated with other cardiovascular risk factors. Additionally, there is no threshold of BP >115/70 mm Hg that identifies cardiovascular risk (i.e., risk is linear and doubles for each 20/10-mm Hg BP rise). These insights have led a group of hypertension experts to propose a new definition of hypertension as "a progressive cardiovascular syndrome arising from complex and interrelated etiologies," which features early markers that are "often present before blood pressure elevation is sustained." Early cardiovascular markers include widened pulse pressure, left ventricular hypertrophy, increased arterial stiffness, endothelial dysfunction, and microalbuminuria. Importantly, antihypertensive treatment for patients with prehypertension (systolic BP of 120-139 mm Hg or diastolic BP of 80-89 mm Hg) has recently been shown to prevent the development of frank hypertension. This revision of the definition of hypertension and the need to assess BP levels in the context of global cardiovascular risk should lead to earlier detection of at-risk patients.

Age Factors↗

Aspects of nitric oxide in health and disease: a focus on hypertension and cardiovascular disease.

Nitric oxide (nitrogen monoxide) (NO) plays an important role in a wide range of physiologic processes. A major mediator of endothelial function, NO regulates vasodilatory and antithrombotic actions in the vasculature and plays a role in reproductive functions, bronchodilation, bone formation, memory, insulin sensitivity, and gastrointestinal relaxation. NO is formed from NO synthase. Impaired NO bioactivity is strongly associated with endothelial dysfunction and cardiovascular disease, but is also implicated in a broad range of other disorders, including pulmonary hypertension, insulin resistance, erectile dysfunction, and preeclampsia. Numerous therapies designed to target NO are being investigated and developed, including NO donors and stimulants. The recent African-American Heart Failure Trial (A-HeFT) showed that the NO donor isosorbide dinitrate, combined with the vasodilator hydralazine, significantly reduced morbidity and mortality in black patients with moderate-to-severe heart failure. Antihypertensive drugs, including angiotensin-converting enzyme inhibitors, calcium channel blockers, and third-generation beta-blockers, are NO stimulants that have demonstrated significant improvement of endothelial function and NO bioactivity. Other cardiovascular therapies that may improve NO bioactivity include statins, l-arginine, and nonpharmacologic approaches such as exercise and dietary changes.

Acetylcholine↗

Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss.

Obesity is becoming a global epidemic in both children and adults, and it is associated with numerous co-morbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, is an independent risk factor for CVD and CVD risks have been also documented in obese children, and is associated with reduced life expectancy. A variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amount. As a whole, overweight/obesity predispose or is associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death through its impact on the cardiovascular system.

Arrhythmias, Cardiac↗

Inhibiting the renin-angiotensin system to prevent cardiovascular diseases: do we need a more comprehensive strategy?

The renin-angiotensin system (RAS) plays a pivotal role in the progression of some forms of hypertension and cardiovascular disease. The development of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has provided physicians with effective and well-tolerated inhibitors of the RAS. However, it remains open to question whether ACE inhibitors and ARBs have fully delivered the reductions in cardiovascular risk that we might have expected. There is little doubt that in conditions such as chronic and acute heart failure or diabetic nephropathy these drugs have provided significant protection. But, in patients with high-risk hypertension, for instance, the anticipated benefits of RAS blockade have been less obvious. This article provides a critical assessment of the results of clinical trials of ACE inhibitors and ARBs across a variety of clinical conditions and assesses the potential need for new methods for blocking the renin system, including the use of renin inhibitors.

Amides↗

Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism.

Obesity is becoming a global epidemic in both children and adults. It is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD, and CVD risks have also been documented in obese children. Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. Besides an altered metabolic profile, a variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amounts, even in the absence of comorbidities. Hence, obesity may affect the heart through its influence on known risk factors such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, obstructive sleep apnea/hypoventilation, and the prothrombotic state, in addition to as-yet-unrecognized mechanisms. On the whole, overweight and obesity predispose to or are associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death because of their impact on the cardiovascular system. The pathophysiology of these entities that are linked to obesity will be discussed. However, the cardiovascular clinical evaluation of obese patients may be limited because of the morphology of the individual. In this statement, we review the available evidence of the impact of obesity on CVD with emphasis on the evaluation of cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system.

American Heart Association↗

Alcohol and the cardiovascular system: research challenges and opportunities.

Excessive alcohol consumption has long been associated with cardiovascular disorders, including cardiomyopathy, hypertension, coronary artery disease, and stroke. However, recent evidence suggests that moderate alcohol intake can actually provide a measure of cardioprotection, particularly against coronary heart disease and ischemia-reperfusion injury. To explore the various dimensions of these opposing actions of alcohol, the National Institute on Alcohol Abuse and Alcoholism and the National Heart, Lung, and Blood Institute sponsored a state-of-the-art workshop on "Alcohol and the Cardiovascular System: Research Challenges and Opportunities" in Bethesda, Maryland, in May 2003. Speakers discussed the following topics: the epidemiology of alcohol and cardiovascular disease, clinical manifestations of alcohol, genetics of alcohol and cardiovascular disease, mechanisms underlying the molecular and cellular effects of alcohol, the application of new and emerging technology, and translation from discovery to therapeutic modalities of treatment. The panel concluded that future studies are needed to: 1) determine the role of genes and the environment in assessing mechanisms underlying the benefits of alcohol use and cardiovascular disease risk; 2) define the biological mechanisms underlying alcohol-induced peripheral vascular damage; 3) clarify the role of genetic variation in alcohol-metabolizing enzymes, genetic susceptibility, and pharmacogenomics in determining cardiovascular disease risk and effective treatment; 4) determine common mechanisms underlying alcohol-induced cardiovascular disease, such as oxidative stress and inflammation; 5) assess the role of insulin resistance, blood clotting, protein kinase C isoforms, and signal transduction mechanisms mediating alcohol's beneficial effects; and 6) explore the potential of stem cells in myocardial regeneration and repair in hearts damaged by alcohol.

Alcohol Drinking↗

Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF.

BACKGROUND: The objective of the current study was to examine the efficacy and tolerability of the beta-blocker metoprolol succinate controlled release/extended release (CR/XL) in patients with diabetes in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF). METHODS: The Cox proportional hazards model was used to calculate hazard ratios (HR) for convenience expressed as relative risks (risk reduction = 1-HR), and 95% confidence intervals (CI). RESULTS: The risk of hospitalization for heart failure was 76% higher in diabetics compared to non-diabetics (95% CI 38% to 123%). Metoprolol CR/XL was well tolerated and reduced the risk of hospitalization for heart failure by 37% in the diabetic group (95% CI 53% to 15%), and by 35% in the non-diabetic group (95% CI 48% to 19%). Pooling of mortality data from the Cardiac Insufficiency Bisoprolol Study II (CIBIS II), MERIT-HF, and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed similar survival benefits in patients with diabetes (25%; 95% CI 40% to 4%) and without diabetes (36%; 95% CI 44% to 27%); test of diabetes by treatment interaction was non-significant. Adverse events were reported more often on placebo than on metoprolol CR/XL. CONCLUSIONS: Patients with heart failure and diabetes have a much higher risk of hospitalization than patients without diabetes. Regardless of diabetic status, a highly significant reduction in hospitalizations for heart failure was observed with metoprolol CR/XL therapy, which was very well tolerated also by patients with diabetes. Furthermore, the pooled data showed a statistically significant survival benefit in patients with diabetes.

Adrenergic beta-Antagonists↗

Treating stage 2 hypertension.

The prevalence of hypertension increases with advancing age, due primarily to increases in systolic blood pressure. Systolic hypertension is the most common form of hypertension in individuals over 50 years of age and reflects pathologic decreases in arterial compliance. Systolic blood pressure elevation is a more important risk factor for cardiovascular disease than is diastolic blood pressure elevation. Stage 2 hypertension, defined as blood pressure > or =160/100 mm Hg, is often found in older persons, who are at highest risk for cardiovascular events. In this clinical review, hypertension experts utilize a case study to provide a paradigm for treating older patients with stage 2 hypertension.

Age Factors↗

Comparative antihypertensive efficacy of angiotensin receptor blocker-based treatment in African-American and white patients.

Blood pressure (BP) reductions with agents that block the renin-angiotensin system are regarded as less effective as monotherapy in African Americans than other ethnic groups. This practice-based study compares the efficacy of an angiotensin receptor blocker-based regimen in African-American and Caucasian patients. Included in the 10-week study were 173 African-American and 1296 Caucasian patients. Efficacy was based on differences in 24-hour ambulatory BP. After baseline ambulatory BP monitoring and office BPs were obtained, all patients were started or switched to the angiotensin receptor blocker telmisartan, 40-80 mg daily, plus hydrochlorothiazide 12.5 mg daily (if needed for office BP control: <140/90 mm Hg). More African Americans required the addition of a low-dose thiazide diuretic than Caucasians (47.3% vs. 34.9%; p=0.021). Once patients with white coat hypertension were excluded (i.e., those with baseline ambulatory BP monitoring <130/80 mm Hg), ambulatory BP monitoring changes were similar between groups. A greater proportion of African Americans than Caucasians without white coat hypertension also needed combination therapy (52.1% vs. 39.5%; p=0.04). While achievement of BP goal was similar between groups by office criterion (<140/90 mm Hg), differences were noted by ambulatory BP monitoring (<130/80 mm Hg) (48.0% in African American vs. 63.2% in Caucasians; p=0.01) despite the same BP reductions, reflecting higher baseline values in African Americans. We conclude that an angiotensin receptor blocker as part of a BP-lowering strategy is effective in previously untreated African-American patients, although a higher proportion will require the use of a diuretic compared with Caucasians.

Adult↗