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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. Summary Given substantial absolute cardiovascular benefits of more intensive antihypertensive therapy in independent-living older adults, this group merits shared-decision making for hypertension targets.

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.

In a randomized trial, 4733 patients with type 2 diabetes mellitus who were at high risk for cardiovascular events received treatment aimed at a target systolic blood pressure of less than 120 mm Hg or less than 140 mm Hg. At a mean follow-up of 4.7 years, the rates of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) were not significantly different between the two trial groups. Patients with type 2 diabetes mellitus who were at high risk for cardiovascular events received treatment aimed at a target systolic blood pressure of less than 120 mm Hg or less than 140 mm Hg. At a mean follow-up of 4.7 years, the rates of the primary end point were not significantly different between the two groups. Diabetes mellitus increases the risk of cardiovascular disease by a factor of two to three at every level of systolic blood pressure. 1 Because cardiovascular risk in patients with diabetes is graded and continuous across the entire range of levels of systolic blood pressure, even at prehypertensive levels, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended beginning drug treatment in patients with diabetes who have systolic blood pressures of 130 mm Hg or higher, with a treatment goal of reducing systolic blood pressure to below 130 mm Hg. . . .

Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes. ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA 1c concentrations (>7·5%), and cardiovascular disease (or ≥2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A 1c [HbA 1c] of <6·0%) or standard (7·0–7·9%) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291·7 μmol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620. 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1·00, 95% CI 0·88–1·14; p=1·00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0·96, 0·89–1·02; p=0·19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0·95, 95% CI 0·85–1·07, p=0·42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0·95, 0·89–1·01, p=0·12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Six secondary measures at study end favoured intensive therapy (p<0·05). Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia. US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.

Catheter-based renal denervation is a new approach to treat hypertension via modulation of the renal sympathetic nerves. Although nonrandomized and small, open-label randomized studies resulted in significant reductions in office blood pressure 6months after renal denervation with monopolar radiofrequency catheters, the first prospective, randomized, sham-controlled study (Symplicity HTN-3) failed to meet its blood pressure efficacy end point. New clinical trials with new catheters have since been designed to address the limitations of earlier studies. Accordingly, the RADIANCE-HTN and REQUIRE studies are multicenter, blinded, randomized, sham-controlled trials designed to assess the blood pressure–lowering efficacy of the ultrasound-based renal denervation system (Paradise) in patients with established hypertension either on or off antihypertensive medications, is designed to evaluate patients in 2 cohorts—SOLO and TRIO, in the United States and Europe. The SOLO cohort includes patients with essential hypertension, at low cardiovascular risk, and either controlled on 1 to 2 antihypertensive medications or uncontrolled on 0 to 2 antihypertensive medications. Patients undergo a 4-week medication washout period before randomization to renal denervation (treatment) or renal angiogram (sham). The TRIO cohort includes patients with hypertension resistant to at least 3 antihypertensive drugs including a diuretic. Patients will be stabilized on a single-pill, triple-antihypertensive-drug combination for 4weeks before randomization to treatment or sham. Reduction in daytime ambulatory systolic blood pressure (primary end point) will be assessed at 2months in both cohorts. A predefined medication escalation protocol, as needed for blood pressure control, is implemented between 2 and 6months in both cohorts by a study staff member blinded to the randomization process. At 6months, daytime ambulatory blood pressure and antihypertensive treatment score will be assessed. REQUIRE is designed to evaluate patients with resistant hypertension on standard of care medication in Japan and Korea. Reduction in 24-hour ambulatory systolic blood pressure will be assessed at 3months (primary end point). Both studies are enrolling patients, and their results are expected in 2018.

Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (DM) and is associated with markers of poor glycemic control; however, the impact of glycemic control on incident AF and outcomes is unknown. The aims of this study were to prospectively evaluate if intensive glycemic control in patients with DM affects incident AF and to evaluate morbidity and mortality in patients with DM and incident AF. A total of 10,082 patients with DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) cohort were studied in a randomized, double-blind fashion. Participants were randomized to an intensive therapeutic strategy targeting a glycated hemoglobin level of <6.0% or a standard strategy targeting a glycated hemoglobin level of 7.0% to 7.9%. Incident AF occurred in 159 patients (1.58%) over the follow-up period, at a rate of 5.9 per 1,000 patient-years in the intensive-therapy group and a rate of 6.37 per 1,000 patient-years in the standard-therapy group (p = 0.52). In a multivariate model, predictors of incident AF were age, weight, diastolic blood pressure, heart rate, and heart failure history. Patients with DM and new-onset AF had a hazard ratio of 2.65 for all-cause mortality (95% confidence interval 1.8 to 3.86, p <0.0001), a hazard ratio of 2.1 for myocardial infarction (95% confidence interval 1.33 to 3.31, p = 0.0015), and a hazard ratio of 3.80 for the development of heart failure (95% confidence interval 2.48 to 5.84, p <0.0001). In conclusion, intensive glycemic control did not affect the rate of new-onset AF. Patients with DM and incident AF had an increased risk for morbidity and mortality compared with those without AF. •Intensive glycemic control did not alter the rate of incident AF.•The investigators describe a number of predictors of AF in patients with diabetes.•Incident AF is associated with adverse outcomes in patients with diabetes.

Background In clinical practice, anthropometric measures other than BMI are rarely assessed yet may be more predictive of cardiovascular (CV) risk. We analyzed the placebo group of the REWIND CV Outcomes Trial to compare several anthropometric measures as baseline risk factors for cardiovascular disease (CVD)-related outcomes in participants with type 2 diabetes (T2D). Methods Data from the REWIND trial placebo group (N = 4952) were analyzed. All participants had T2D, age ≥ 50 years, had either a previous CV event or CV risk factors, and a BMI of ≥ 23 kg/m 2 . Cox proportional hazard models were used to investigate if BMI, waist-to-hip ratio (WHR), and waist circumference (WC) were significant risk factors for major adverse CV events (MACE)-3, CVD-related mortality, all-cause mortality, and heart failure (HF) requiring hospitalization. Models were adjusted for age, sex, and additional baseline factors selected by LASSO method. Results are presented for one standard deviation increase of the respective anthropometric factor. Results Participants in the placebo group experienced 663 MACE-3 events, 346 CVD-related deaths, 592 all-cause deaths, and 226 events of HF requiring hospitalization during the median follow-up of 5.4 years. WHR and WC, but not BMI, were identified as independent risk factors of MACE-3 (hazard ratio [HR] for WHR: 1.11 [95% CI 1.03 to 1.21]; p = 0.009; HR for WC: 1.12 [95% CI 1.02 to 1.22]; p = 0.012). WC adjusted for hip circumference (HC) showed the strongest association with MACE-3 compared to WHR, WC, or BMI unadjusted for each other (HR: 1.26 [95% CI 1.09 to 1.46]; p = 0.002). Results for CVD-related mortality and all-cause mortality were similar. WC and BMI were risk factors for HF requiring hospitalization, but not WHR or WC adjusted for HC (HR for WC: 1.34 [95% CI 1.16 to 1.54]; p < 0.001; HR for BMI: 1.33 [95% CI 1.17 to 1.50]; p < 0.001). No significant interaction with sex was observed. Conclusions In this post hoc analysis of the REWIND placebo group, WHR, WC and/or WC adjusted for HC were risk factors for MACE-3, CVD-related mortality, and all-cause mortality; while BMI was only a risk factor for HF requiring hospitalization. These findings indicate the need for anthropometric measures that consider body fat distribution when assessing CV risk.

Hypertension affects up to 50% of US adults and resistant hypertension (rHTN) occurs in 10-20% of cases. Endogenous hypercortisolism (eHC) may contribute to rHTN in some individuals, but the prevalence of eHC in individuals with rHTN is currently unknown. The CATALYST study assessing eHC prevalence in individuals with difficult-to-control type 2 diabetes, reported a 40% prevalence of eHC in participants with systolic blood pressure (BP) ≥135 mm Hg despite taking ≥3 BP medications (Handelsman Y, et al. WCIRDC 2024. Poster 0050). MOMENTUM is the first large, prospective study to examine the prevalence of eHC in people with rHTN in the US. MOMENTUM is an observational study of ∼1,000 adults with rHTN using American Heart Association criteria. Key exclusion criteria are investigator-determined white coat hypertension, nonadherence to BP medications, and individuals in whom the dexamethasone suppression test is difficult to interpret. The primary endpoint is to assess the eHC prevalence in this population. Key secondary endpoints are to assess clinical and laboratory features associated with increased eHC risk. Hyperaldosteronism will also be screened for. Descriptive statistics will be used to characterize participants with and without eHC. In conclusion, the MOMENTUM study, as designed and currently enrolling, will provide an estimate of eHC prevalence and its associated clinical characteristics in people with rHTN. (ClinicalTrials.gov Identifier: NCT06829537)

The fixed-dose combination of any two antihypertensive drugs from different drug classes is typically more effective in reducing blood pressure than a dose increase of component monotherapy. We assessed the efficacy and safety of a fixed-dose combination of a vasodilating β blocker (nebivolol) and an angiotensin II receptor blocker (valsartan) in adults with hypertension. We did an 8-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group trial at 401 US sites. Participants (age ≥18 years) with hypertension but with blood pressure less than 180/110 mm Hg were randomly assigned (2:2:2:2:2:2:2:1) by a 24-h interactive web response system in blocks of 15 to 4 weeks of double-blind treatment with nebivolol and valsartan fixed-dose combination (5 and 80 mg/day, 5 and 160 mg/day, or 10 and 160 mg/day), nebivolol (5 mg/day or 20 mg/day), valsartan (80 mg/day or 160 mg/day), or placebo. Doses were doubled in weeks 5–8; results are reported according to the final dose. Participants and research staff were masked to treatment allocation. The primary and key secondary endpoints were changes from baseline to week 8 in diastolic and systolic blood pressure, respectively. The primary statistical comparison was between the highest fixed-dose combination dose and the highest monotherapy doses; lower doses were then compared if this comparison was positive (Hochberg method for multiple testing). Efficacy analyses were by intention to treat. Safety assessments included monitoring of adverse events. Continuous efficacy parameters were analysed using an ANCOVA model; binary outcomes were analysed using a logistic regression model. This study is registered with ClinicalTrials.gov, NCT01508026. Between Jan 6, 2012, and March 15, 2013, 4161 patients were randomly assigned (277 to placebo and 554–555 to each active comparator group), 4118 of whom were included in the primary analysis. At week 8, the fixed-dose combination 20 and 320 mg/day group had significantly greater reductions in diastolic blood pressure from baseline than both nebivolol 40 mg/day (least-squares mean difference −1·2 mm Hg, 95% CI −2·3 to −0·1; p=0·030) and valsartan 320 mg/day (−4·4 mm Hg, −5·4 to −3·3; p<0·0001); all other comparisons were also significant, favouring the fixed-dose combinations (all p<0·0001). All systolic blood pressure comparisons were also significant (all p<0·01). At least one treatment-emergent adverse event was experienced by 30–36% of participants in each group. Nebivolol and valsartan fixed-dose combination is an effective and well-tolerated treatment option for patients with hypertension. Forest Research Institute.

The blood pressure (BP) lowering response to renal denervation (RDN) remains variable with about one-third of patients not responding to ultrasound or radiofrequency RDN. Identification of predictors of the BP response to RDN is needed to optimize patient selection for this therapy. This is a post-hoc analysis of the RADIANCE-HTN SOLO study. BP response to RDN was measured by the change in daytime ambulatory systolic blood pressure (dASBP) at 2 months post procedure. Univariate regression was used initially to assess potential predictors of outcome followed by multivariate regression analysis. In the univariate analysis, predictors of response to RDN were higher baseline daytime ambulatory diastolic blood pressure (dADBP), the use of antihypertensive medications at screening, and presence of orthostatic hypertension (OHTN) whilst the presence of untreated accessory arteries was a negative predictor of response. Multivariate analysis determined that dADBP and use of antihypertensive medications were predictors of response to RDN with a trend for OHTN to predict response. Obese females also appeared to be better responders to RDN in an interaction model. RDN is more effective in patients with elevated baseline dADBP and those with OHTN, suggesting increased peripheral vascular resistance secondary to heightened sympathetic tone. These assessments are easy to perform in clinical setting and may help in phenotyping patients who will respond better to RDN.