Edward D. Frohlich

Diabetes, Hypertension, and Cardiovascular Disease: An Update

Abstract—Cardiovascular diseases (CVDs) are the major causes of mortality in persons with diabetes, and many factors, including hypertension, contribute to this high prevalence of CVD. Hypertension is approximately twice as frequent in patients with diabetes compared with patients without the disease. Conversely, recent data suggest that hypertensive persons are more predisposed to the development of diabetes than are normotensive persons. Furthermore, up to 75% of CVD in diabetes may be attributable to hypertension, leading to recommendations for more aggressive treatment (ie, reducing blood pressure to <130/85 mm Hg) in persons with coexistent diabetes and hypertension. Other important risk factors for CVD in these patients include the following: obesity, atherosclerosis, dyslipidemia, microalbuminuria, endothelial dysfunction, platelet hyperaggregability, coagulation abnormalities, and “diabetic cardiomyopathy.” The cardiomyopathy associated with diabetes is a unique myopathic state that appears to be independent of macrovascular/microvascular disease and contributes significantly to CVD morbidity and mortality in diabetic patients, especially those with coexistent hypertension. This update reviews the current knowledge regarding these risk factors and their treatment, with special emphasis on the cardiometabolic syndrome, hypertension, microalbuminuria, and diabetic cardiomyopathy. This update also examines the role of the renin-angiotensin system in the increased risk for CVD in diabetic patients and the impact of interrupting this system on the development of clinical diabetes as well as CVD.

The heart in hypertension.

HYPERTENSIVE heart disease can be defined as the response of the heart to the afterload imposed on the left ventricle by the progressively increasing arterial pressure and total peripheral resistance produced by hypertensive vascular disease. Although the response sometimes appears to be out of proportion to the level of the arterial pressure, it is primarily the result of the hemodynamic overload. Hypertension can cause or is related to various cardiac manifestations, among them left ventricular hypertrophy, congestive heart failure, cardiac dysrhythmias, and ischemic heart disease. Although the risk of atherosclerotic coronary heart disease is related to the systolic and diastolic .xa0.xa0.

The Importance of Population-Wide Sodium Reduction as a Means to Prevent Cardiovascular Disease and Stroke A Call to Action From the American Heart Association

Blood pressure (BP)-related diseases, specifically, stroke, coronary heart disease, heart failure, and kidney disease, are leading causes of morbidity and mortality in the United States and throughout the world. In the United States, coronary heart disease and stroke are the leading causes of mortality, whereas heart failure is the leading cause of hospitalizations.1 Concurrently, the prevalence of chronic kidney disease remains high and is escalating.2,3 The direct and indirect costs of these conditions are staggering, over

Sodium, Blood Pressure, and Cardiovascular Disease Further Evidence Supporting the American Heart Association Sodium Reduction Recommendations

400 billion just for cardiovascular disease (CVD) in 2009.1,4 The human consequences are likewise enormous.nnThe relation between BP and adverse health outcomes is direct and progressive with no evidence of a threshold, that is, the risk of CVD, stroke, and end-stage kidney disease increases progressively throughout the range of usual BP starting at a level of ≈115/75 mm Hg.5,–,7 Overall, elevated BP is the second leading modifiable cause of death, accounting for an estimated 395 000 preventable deaths in the United States in 2005.8 Worldwide, elevated BP accounts for 54% of stroke and 47% of coronary heart disease events; importantly, about half of these events occur in persons without hypertension.9nnThe 2020 goal of the American Heart Association (AHA) is to improve the cardiovascular heath of all Americans by 20% while continuing to reduce deaths from CVD and stroke by 20%.4 Two of the key metrics for ideal cardiovascular health are a BP of <120/80 mm Hg and sodium consumption of <1500 mg/d. The purpose of this advisory is 2-fold: first is to highlight the impressive body of evidence that links sodium intake with elevated BP and other adverse outcomes, and second, to serve as a call to action on behalf of the AHA for individuals, healthcare providers, …

Re-Examination of the Hemodynamics of Hypertension

Recent reports of selected observational studies and a meta-analysis have stirred controversy and have become the impetus for calls to abandon recommendations for reduced sodium intake by the US general population. A detailed review of these studies documents substantial methodological concerns that limit the usefulness of these studies in setting, much less reversing, dietary recommendations. Indeed, the evidence base supporting recommendations for reduced sodium intake in the general population remains robust and persuasive. The American Heart Association is committed to improving the health of all Americans through implementation of national goals for health promotion and disease prevention, including its recommendation to reduce dietary sodium intake to <1500 mg/d.

Salt in Health and Disease — A Delicate Balance

Increased vascular resistance has been considered the hemodynamic hallmark of hypertension since cardiac output has been reported as normal. This assumption was reinvestigated in 25 normotensive subjects and 117 untreated hypertensive patients whose complete evaluation, including renal arteriography, permitted classification of type of hypertension. When the entire hypertensive group by itself was compared with the normals, the traditional conclusion was corroborated; elevated arterial pressure was associated only with increased vascular resistance. However, hemodynamic findings differed significantly when each type of hypertension was studied separately. Thus, cardiac output was normal in pheochromocytoma, renal parenchymal disease, and primary aldosteronism, increased in renal arterial disease (p < .001) and labile hypertension (p < .05), and reduced or low normal (p < .05) in essential hypertension. When essential hypertensive patients were subdivided into those with and without cardiac enlargement, output was reduced (p < .02) in those with nonfailing cardiac enlargement; but all, whether having normal or enlarged hearts had lower output than patients with renal arterial disease (p < .001). Peripheral resistance was elevated in all patients except those with labile hypertension. Therefore, hypertension no longer should be considered a homogeneous disease ascribed only to increased vascular resistance; hemodynamics vary significantly depending upon type and stage of disease.

Predictors of Decline in Medication Adherence: Results From the Cohort Study of Medication Adherence Among Older Adults

This review provides an overview of our current understanding of the relation of salt consumption to hypertension and cardiovascular disease.

Association of Depression with Antihypertensive Medication Adherence in Older Adults: Cross-Sectional and Longitudinal Findings from CoSMO

Few data are available on the predictors of decline in antihypertensive medication adherence and the association of decline in adherence with subsequent blood pressure (BP) control. The current analysis included 1,965 adults from the Cohort Study of Medication Adherence among Older Adults (CoSMO) recruited between August 2006 and September 2007. Decline in antihypertensive medication adherence was defined as a ≥ 2 point decrease on the 8-item Morisky Medication Adherence Scale assessed during telephone surveys 1 and 2 years following baseline. Risk factors for decline in adherence were collected using telephone surveys and administrative databases. BP was abstracted from outpatient records. The annual rate for a decline in adherence was 4.3% (159 participants experienced a decline). After multivariable adjustment, a decline in adherence was associated with an odds ratio (OR) for uncontrolled BP (≥140/90 mm Hg) at follow up of 1.68 (95% CI: 1.01, 2.80). Depressive symptoms (OR 1.84, 95%CI 1.20, 2.82) and a high stressful life events score (OR 1.68, 95% CI 1.19, 2.38) were associated with higher ORs for a decline in adherence. Female gender (OR 0.61, 95% CI 0.42, 0.88); being married (OR 0.68, 95% CI 0.47, 0.98); and calcium channel blocker use (OR 0.68, 95% CI 0.48, 0.97) were associated with lower ORs for decline. In summary, a decline in antihypertensive medication adherence was associated with uncontrolled BP. Modifiable factors associated with decline were identified. Further research is warranted to determine if interventions can prevent the decline in antihypertensive medication adherence and improve BP control.Few data are available on the predictors of decline in antihypertensive medication adherence and the association of decline in adherence with subsequent blood pressure (BP) control. The current analysis included 1965 adults from the Cohort Study of Medication Adherence Among Older Adults recruited between August 2006 and September 2007. Decline in antihypertensive medication adherence was defined as a ≥2-point decrease on the 8-item Morisky Medication Adherence Scale assessed during telephone surveys 1 and 2 years after baseline. Risk factors for decline in adherence were collected using telephone surveys and administrative databases. BP was abstracted from outpatient records. The annual rate for a decline in adherence was 4.3% (159 participants experienced a decline). After multivariable adjustment, a decline in adherence was associated with an odds ratio (OR) for uncontrolled BP (≥140/90 mm Hg) at follow-up of 1.68 (95% CI: 1.01–2.80). Depressive symptoms (OR: 1.84 [95% CI: 1.20–2.82]) and a high stressful life events score (OR: 1.68 [95% CI: 1.19–2.38]) were associated with higher ORs for a decline in adherence. Female sex (OR: 0.61 [95% CI: 0.42–0.88]), being married (OR: 0.68 [95% CI: 0.47–0.98]), and calcium channel blocker use (OR: 0.68 [95% CI: 0.48–0.97]) were associated with lower ORs for decline. In summary, a decline in antihypertensive medication adherence was associated with uncontrolled BP. Modifiable factors associated with decline were identified. Further research is warranted to determine whether interventions can prevent the decline in antihypertensive medication adherence and improve BP control.

Identifying Patients at High Risk of a Cardiovascular Event in the Near Future: Current Status and Future Directions: Report of a National Heart, Lung, and Blood Institute Working Group

BackgroundLittle is known about the associations between depressive symptoms, social support and antihypertensive medication adherence in older adults.PurposeWe evaluated the cross-sectional and longitudinal associations between depressive symptoms, social support and antihypertensive medication adherence in a large cohort of older adults.Methods A cohort of 2,180 older adults with hypertension was administered questionnaires, which included the Center for Epidemiologic Studies-Depression Scale, the Medical Outcomes Study Social Support Index, and the hypertension-specific Morisky Medication Adherence Scale at baseline and 1xa0year later.ResultsOverall, 14.1% of participants had low medication adherence, 13.0% had depressive symptoms, and 33.9% had low social support. After multivariable adjustment, the odds ratios that participants with depressive symptoms and low social support would have low medication adherence were 1.96 (95% confidence interval (CI) 1.43, 2.70) and 1.27 (95% CI 0.98, 1.65), respectively, at baseline and 1.87 (95% CI 1.32, 2.66) and 1.30 (95% CI 0.98, 1.72), respectively, at 1xa0year follow-up.ConclusionDepressive symptoms may be an important modifiable barrier to antihypertensive medication adherence in older adults

Apoptosis, Coronary Arterial Remodeling, and Myocardial Infarction After Nitric Oxide Inhibition in SHR

The National Heart, Lung, and Blood Institute convened a working group to provide basic and clinical research recommendations to the National Heart, Lung, and Blood Institute on the development of an integrated approach for identifying those individuals who are at high risk for a cardiovascular event such as acute coronary syndromes (ACS) or sudden cardiac death in the “near term.” The working group members defined near-term as occurring within 1 year of the time of assessment. The participants reviewed current clinical cardiology practices for risk assessment and state-of-the-science techniques in several areas, including biomarkers, proteomics, genetics, psychosocial factors, imaging, coagulation, and vascular and myocardial susceptibility. This report presents highlights of these reviews and a summary of suggested research directions.nn### Near-Term RisknnThe proper deployment of preventive strategies requires an accurate classification system that allows the physician to target intensive treatments to the highest-risk patients. A commonly recommended approach is a multivariable assessment such as the Framingham Risk Score (FRS).1 Although the FRS is recommended in many guidelines on cardiovascular risk assessment,2 it has some limitations. It does not include several factors of the metabolic syndrome (glucose intolerance, central obesity, and hypertriglyceridemia), nor does it include family history. Moreover, the FRS classifies risk over a period of 10 years rather than in the near term (within 1 year). Indeed, no algorithm has been developed that accurately predicts near-term risk across diverse populations.nnThe ability to forecast near-term risk of ACS or sudden cardiac death would represent an important advance in cardiovascular medicine because it would clarify which individuals are in most urgent need of intervention. It would help identify those rare asymptomatic, apparently healthy individuals who are in imminent danger of a cardiovascular event yet ordinarily would not receive therapy at all. In asymptomatic individuals judged to be at intermediate or …