Managing Hypertension in Older Adults.

PURPOSE OF REVIEW: The population of older adults 60-79 years globally is projected to double from 800 million to 1.6 billion between 2015 and 2050, while adults ≥ 80 years were forecast to more than triple from 125 to 430 million. The risk for cardiovascular events doubles with each decade of aging and each 20 mmHg increase of systolic blood pressure. Thus, successful management of hypertension in older adults is critical in mitigating the projected global health and economic burden of cardiovascular disease. RECENT FINDINGS: Women live longer than men, yet with aging systolic blood pressure and prevalent hypertension increase more, and hypertension control decreases more than in men, i.e., hypertension in older adults is disproportionately a women's health issue. Among older adults who are healthy to mildly frail, the absolute benefit of hypertension control, including more intensive control, on cardiovascular events is greater in adults ≥ 80 than 60-79 years old. The absolute rate of serious adverse events during antihypertensive therapy is greater in adults ≥ 80 years older than 60-79 years, yet the excess adverse event rate with intensive versus standard care is only moderately increased. Among adults ≥ 80 years, benefits of more intensive therapy appear non-existent to reversed with moderate to marked frailty and when cognitive function is less than roughly the twenty-fifth percentile. Accordingly, assessment of functional and cognitive status is important in setting blood pressure targets in older adults. Given substantial absolute cardiovascular benefits of more intensive antihypertensive therapy in independent-living older adults, this group merits shared-decision making for hypertension targets.

How We Got Where We Are in Blood Pressure Targets.

PURPOSE OF REVIEW: While we started clinical trials evaluating the benefit of lowering systolic BP's >160 mm Hg and diastolic BPs of <130 mm Hg, the latest guideline suggests a target of <130/80 mm Hg in those with hypertension. This article summarizes exactly how we got to where we are looking over the last half-century. RECENT FINDINGS: Our understanding of systolic and diastolic blood pressure targets to improve cardiovascular outcomes has changed substantially over the past 5 decades. Regarding diastolic blood pressure targets to improve cardiovascular outcomes, initially the VA1 in 1967 had set the goal to <115 mmHg. Over time, several studies including the VA2, Hypertension Optimal Treatment (HOT), and United Kingdom Prospective Diabetes Study Group 38 (UKPDS38) highlighted even greater cardiovascular benefit with lower diastolic targets <80 mmHg, especially in diabetic patients. Of equal importance, multiple studies have focused the attention to systolic blood pressure targets. Starting in 1948 with the Framingham study, passing through the Systolic Hypertension in the Elderly Program (SHEP), Syst-Eur and Syst-China trials, all have set the systolic blood pressure goal <150 mmHg. Most recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed an improved cardiovascular outcome with a systolic blood pressure target <140 mmHg in patients with type 2 diabetes, while the Systolic Blood Pressure Intervention Trial (SPRINT) in non-diabetic patients moved it closer to 120 mmHg. There is "no one size fits all" when it comes to blood pressure targets to improve cardiovascular outcomes. To progress our understanding of individual blood pressure goals, future studies might develop a more standardized approach to highlight characteristics such as design and end point definitions while allowing clinical practitioners greater latitude to adapt guideline recommendations to individual patient characteristics and clinical needs.

Self-Measured Blood Pressure Monitoring at Home: A Joint Policy Statement From the American Heart Association and American Medical Association.

The diagnosis and management of hypertension, a common cardiovascular risk factor among the general population, have been based primarily on the measurement of blood pressure (BP) in the office. BP may differ considerably when measured in the office and when measured outside of the office setting, and higher out-of-office BP is associated with increased cardiovascular risk independent of office BP. Self-measured BP monitoring, the measurement of BP by an individual outside of the office at home, is a validated approach for out-of-office BP measurement. Several national and international hypertension guidelines endorse self-measured BP monitoring. Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of white-coat effect and masked uncontrolled hypertension. Other indications include confirming the diagnosis of resistant hypertension and detecting morning hypertension. Validated self-measured BP monitoring devices that use the oscillometric method are preferred, and a standardized BP measurement and monitoring protocol should be followed. Evidence from meta-analyses of randomized trials indicates that self-measured BP monitoring is associated with a reduction in BP and improved BP control, and the benefits of self-measured BP monitoring are greatest when done along with cointerventions. The addition of self-measured BP monitoring to office BP monitoring is cost-effective compared with office BP monitoring alone or usual care among individuals with high office BP. The use of self-measured BP monitoring is commonly reported by both individuals and providers. Therefore, self-measured BP monitoring has high potential for improving the diagnosis and management of hypertension in the United States. Randomized controlled trials examining the impact of self-measured BP monitoring on cardiovascular outcomes are needed. To adequately address barriers to the implementation of self-measured BP monitoring, financial investment is needed in the following areas: improving education and training of individuals and providers, building health information technology capacity, incorporating self-measured BP readings into clinical performance measures, supporting cointerventions, and enhancing reimbursement.

Orthostatic Hypotension in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Blood Pressure Trial: Prevalence, Incidence, and Prognostic Significance.

Orthostatic hypotension (OH) is associated with hypertension and diabetes mellitus. However, in populations with both hypertension and diabetes mellitus, its prevalence, the effect of intensive versus standard systolic blood pressure (BP) targets on incident OH, and its prognostic significance are unclear. In 4266 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial, seated BP was measured 3×, followed by readings every minute for 3 minutes after standing. Orthostatic BP change, calculated as the minimum standing minus the mean seated systolic BP and diastolic BP, was assessed at baseline, 12 months, and 48 months. The relationship between OH and clinical outcomes (total and cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization or death and the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) was assessed using proportional hazards analysis. Consensus OH, defined by orthostatic decline in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, occurred at ≥1 time point in 20% of participants. Neither age nor systolic BP treatment target (intensive, <120 mm Hg versus standard, <140 mm Hg) was related to OH incidence. Over a median follow-up of 46.9 months, OH was associated with increased risk of total death (hazard ratio, 1.61; 95% confidence interval, 1.11-2.36) and heart failure death/hospitalization (hazard ratio, 1.85, 95% confidence interval, 1.17-2.93), but not with the primary outcome or other prespecified outcomes. In patients with type 2 diabetes mellitus and hypertension, OH was common, not associated with intensive versus standard BP treatment goals, and predicted increased mortality and heart failure events.

Cardiovascular Outcomes According to Systolic Blood Pressure in Patients With and Without Diabetes: An ACCOMPLISH Substudy.

To evaluate the effects of achieved systolic blood pressure (SBP) during treatment on cardiovascular (CV) outcomes, the authors measured event rates of a composite primary endpoint (CV death or nonfatal myocardial infarction or stroke) at on-treatment SBPs of ≥140 mm Hg and the 10 mm Hg intervals of <140 mm Hg, <130 mm Hg, and <120 mm Hg in 6459 patients with diabetes (mean age, 67) and 4246 patients without diabetes (mean age, 69) from the Avoiding Cardiovascular Events in Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial. In the diabetic cohort, the primary endpoint was 49% lower (P<.001) at <140 mm Hg than at ≥140 mm Hg, and the separate components of this endpoint were also significantly reduced. Further SBP reductions did not improve outcomes, and at <120 mm Hg they were no longer different (except for stroke) from ≥140 mm Hg. In contrast, in the nondiabetic cohort, the primary endpoint event rate fell steadily (although not significantly) through the decreasing SBP categories until it was reduced by 45% (P=.0413) at <120 mm Hg. Total stroke rates for both the diabetic (-56%, P=.0120) and nondiabetic (-68%, P=.0067) cohorts were lowest at <120 mm Hg, and adverse renal events (serum creatinine increase ≥50%) were significantly lowest in the range of 130 mm Hg to 139 mm Hg for both cohorts. Diabetic patients (<140 mm Hg or <130 mm Hg) and nondiabetic patients (<120 mm Hg) may require different SBP targets for optimal CV protection, although stroke and renal considerations should also influence the selection of blood pressure targets.

A Multifactorial Approach to Reduce Cardiovascular Disease in Type 2 Diabetes Mellitus: Now More Than Ever.

Managing cardiovascular (CV) risk is an important part of caring for patients with type 2 diabetes mellitus, as the disease itself confers CV risk. Many CV risk factors (such as hypertension, dyslipidemia, and obesity) have been found to be more common among individuals with diabetes than in the general population. A growing body of evidence provides guidance for clinicians on how to balance control of hyperglycemia with management of these risk factors. Newer classes of antihyperglycemic agents have been associated with beneficial effects on several CV risk factors; several studies evaluating the effect of these newer diabetic medications on CV outcomes have been published, and several more are in progress. While evidence continues to unfold about the benefits of risk factor control in patients with type 1 diabetes mellitus, this article reviews evidence related to risk-factor control in patients with type 2 diabetes mellitus as well as recent findings on the effect of newer drug classes on CV risk factors and outcomes. Favorably altering CV risk factors appears to improve outcomes, and is more important now than ever before.

Characteristics and long-term follow-up of participants with peripheral arterial disease during ALLHAT.

BACKGROUND: Hypertension is a major risk factor for peripheral artery disease (PAD). Little is known about relative efficacy of antihypertensive treatments for preventing PAD. OBJECTIVES: To compare, by randomized treatment groups, hospitalized or revascularized PAD rates and subsequent morbidity and mortality among participants in the Antihypertensive and Lipid-Lower Treatment to Prevent Heart Attack Trial (ALLHAT). DESIGN: Randomized, double-blind, active-control trial in high-risk hypertensive participants. PARTICIPANTS: Eight hundred thirty participants with specified secondary outcome of lower extremity PAD events during the randomized phase of ALLHAT. INTERVENTIONS/EVENTS: In-trial PAD events were reported during ALLHAT (1994-2002). Post-trial mortality data through 2006 were obtained from administrative databases. Mean follow-up was 8.8 years. MAIN MEASURES: Baseline characteristics and intermediate outcomes in three treatment groups, using the Kaplan-Meier method to calculate cumulative event rates and post-PAD mortality rates, Cox proportional hazards regression model for hazard ratios and 95 % confidence intervals, and multivariate Cox regression models to examine risk differences among treatment groups. KEY RESULTS: Following adjustment for baseline characteristics, neither participants assigned to the calcium-channel antagonist amlodipine nor to the ACE-inhibitor lisinopril showed a difference in risk of clinically advanced PAD compared with those in the chlorthalidone arm (HR, 0.86; 95 % CI, 0.72-1.03 and HR, 0.98; 95 % CI, 0.83-1.17, respectively). Of the 830 participants with in-trial PAD events, 63 % died compared to 34 % of those without PAD; there were no significant treatment group differences for subsequent nonfatal myocardial infarction, coronary revascularizations, strokes, heart failure, or mortality. CONCLUSIONS: Neither amlodipine nor lisinopril showed superiority over chlorthalidone in reducing clinically advanced PAD risk. These findings reinforce the compelling need for comparative outcome trials examining treatment of PAD in high-risk hypertensive patients. Once PAD develops, cardiovascular event and mortality risk is high, regardless of type of antihypertensive treatment.

Renal sympathetic denervation for blood pressure control: a review of the current evidence and ongoing studies.

Hypertensive heart disease is the leading cause of mortality and morbidity in the United States. Despite widespread availability of medical therapy, it remains a challenge to treat. Autonomic nervous system imbalance resulting in overactivity of the sympathetic nervous system is integral to the development of hypertension and ultimately the development of hypertensive heart disease. Although the results with renal sympathetic denervation so far have been encouraging, optimism has recently been tempered with the broadcast alert from Medtronic, the sponsor of Symplicity HTN-3, that the trial did not meet its primary efficacy endpoint. The principal focus of this article is to review the developments in renal sympathetic denervation for the treatment of resistant hypertension.

Pravastatin and cardiovascular outcomes stratified by baseline eGFR in the lipid- lowering component of ALLHAT.

BACKGROUND/AIMS: The role of statins in preventing cardiovascular outcomes in patients with chronic kidney disease (CKD) is unclear. This paper compares cardiovascular outcomes with pravastatin vs. usual care, stratified by baseline estimated glomerular filtration rate (eGFR). METHODS: Post-hoc analyses of a prospective randomized open-label clinical trial; 10,151 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) were randomized to pravastatin 40 mg/day or usual care. Mean follow-up was 4.8 years. RESULTS: Through Year 6, total cholesterol declined in pravastatin (-20.7%) and usualcare groups (-11.2%). Use of statin therapy in the pravastatin group was 89.8% (Year 2) and 87.0% (Year 6). Usual-care group statin use increased from 8.2% (Year 2) to 23.5% (Year 6). By primary intention-to-treat analyses, no significant differences were seen between groups for coronary heart disease (CHD), total mortality or combined cardiovascular disease; findings were consistent across eGFR strata. In exploratory "as-treated" analyses (patients actually using pravastatin vs. not using), pravastatin therapy was associated with lower mortality (HR = 0.76 (0.68 - 0.85), p<0.001) and lover CHD (HR=0.84 (0.73-0.97), p=0.01), but not combined cardiovascular disease (HR=0.95 (0.88-1.04), p=0.30). Total cholesterol reduction of 10 mg/dl from baseline to Year 2 was associated with 5% lower CHD risk. CONCLUSIONS: In hypertensive patients with moderate dyslipidemia, pravastatin was not superior to usual care in preventing total mortality or CHD independent of baseline eGFR level. However, exploratory "as-treated" analyses suggest improved mortality and CHD risk in participants using pravastatin, and decreased CHD events associated with achieved reduction in total cholesterol. Potential benefit from statin therapy may depend on degree of reduction achieved in total and LDL-cholesterol and adherence to therapy.

The potential of sodium glucose cotransporter 2 (SGLT2) inhibitors to reduce cardiovascular risk in patients with type 2 diabetes (T2DM).

Type 2 diabetes mellitus (T2DM) significantly increases morbidity and mortality from cardiovascular disease (CVD). Treatments for patients with T2DM have the potential to reduce cardiovascular (CV) risk. This review focuses on the potential of a new class of antidiabetic agents, the sodium glucose cotransporter 2 (SGLT2) inhibitors, to reduce CV risk in patients with T2DM through reductions in hyperglycemia, blood pressure (BP), and body weight. The results of clinical trials of SGLT2 inhibitors are summarized and discussed.