Nonadherence to antihypertensive treatment is a critical contributor to suboptimal blood pressure control. There are limited and heterogeneous data on the risk factors for nonadherence because few studies used objective-direct diagnostic methods. We used high-performance liquid chromatography-tandem mass spectrometry of urine and serum to detect nonadherence and explored its association with the main demographic- and therapy-related factors in 1348 patients with hypertension from 2 European countries. The rates of nonadherence to antihypertensive treatment were 41.6% and 31.5% in the UK and Czech populations, respectively. Nonadherence was inversely related to age and male sex. Each increase in the number of antihypertensive medications led to 85% and 77% increase in nonadherence (P<0.001) in the UK and Czech populations, respectively. The odds of nonadherence to diuretics were the highest among 5 classes of antihypertensive medications (P≤0.005 in both populations). The predictive model for nonadherence, including age, sex, diuretics, and the number of prescribed antihypertensives, showed area under the curves of 0.758 and 0.710 in the UK and Czech populations, respectively. The area under the curves for the UK model tested on the Czech data and for the Czech model tested on UK data were calculated at 0.708 and 0.756, respectively. We demonstrate that the number and class of prescribed antihypertensives are modifiable risk factors for biochemically confirmed nonadherence to blood pressure–lowering therapy. Further development of discriminatory models incorporating these parameters might prove clinically useful in assessment of nonadherence in countries where biochemical analysis is unavailable.

We hypothesized that screening for nonadherence to antihypertensive treatment using liquid chromatography-tandem mass spectrometry–based biochemical analysis of urine/serum has therapeutic applications in nonadherent hypertensive patients. A retrospective analysis of hypertensive patients attending specialist tertiary care centers was conducted in 2 European countries (United Kingdom and Czech Republic). Nonadherence to antihypertensive treatment was diagnosed using biochemical analysis of urine (United Kingdom) or serum (Czech Republic). These results were subsequently discussed with each patient, and data on follow-up clinic blood pressure (BP) measurements were collected from clinical files. Of 238 UK patients who underwent biochemical urine analysis, 73 were nonadherent to antihypertensive treatment. Their initial urinary adherence ratio (the ratio of detected to prescribed antihypertensive medications) increased from 0.33 (0–0.67) to 1 (0.67–1) between the first and the last clinic appointments. The observed increase in the urinary adherence ratio in initially nonadherent UK patients was associated with the improved BP control; by the last clinic appointment, systolic and diastolic BPs were ≈19.5 and 7.5 mm Hg lower than at baseline (P=0.001 and 0.009, respectively). These findings were further corroborated in 93 nonadherent hypertensive patients from Czech Republic—their average systolic and diastolic BPs dropped by ≈32.6 and 17.4 mm Hg, respectively (P<0.001), on appointments after the biochemical analysis. Our data show that nonadherent hypertensive patients respond to liquid chromatography–tandem mass spectrometry-based biochemical analysis with improved adherence and significant BP drop. Such repeated biochemical analyses should be considered as a therapeutic approach in nonadherent hypertensive patients.

The prevalence of type 2 diabetes (T2D) has reached a pandemic scale. These patients are at a substantially elevated risk of developing cardiovascular disease, with heart failure (HF) being a leading cause of morbidity and mortality. Even in the absence of traditional risk factors, diabetes still confers up to a twofold increased risk of developing HF. This has led to identifying diabetes as an independent risk factor for HF and recognition of the distinct clinical entity, diabetic cardiomyopathy. Despite a wealth of research interest, the prevalence and determinants of diabetic cardiomyopathy remain uncertain. This limited understanding of the pathophysiology of diabetic heart disease has also hindered development of effective treatments. Tight blood-glucose and blood-pressure control have not convincingly been shown to reduce macrovascular outcomes in T2D. There is, however, emerging evidence that T2D is reversible and that the metabolic abnormalities can be reversed with weight loss. Increased aerobic exercise capacity is associated with significantly lower cardiovascular and overall mortality in diabetes. Whether such lifestyle modifications as weight loss and exercise may ameliorate the structural and functional derangements of the diabetic heart has yet to be established. In this review, the link between T2D and myocardial dysfunction is explored. Insights into the structural and functional perturbations that typify the diabetic heart are first described. This is followed by an examination of the pathophysiological mechanisms that contribute to the development of cardiovascular disease in T2D. Lastly, the current and emerging therapeutic strategies to prevent or ameliorate cardiac dysfunction in T2D are evaluated.

OBJECTIVE: To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training. RESEARCH DESIGN AND METHODS: This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (∼810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison. RESULTS: Eighty-seven participants with T2D (age 51 ± 7 years, HbA1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s−1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, LV mass/volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (β = 0.132, P = 0.002) but did not improve with the MRP (β = 0.016, P = 0.731). CONCLUSIONS: In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function.

Heart failure is a major cause of morbidity and mortality in type 2 diabetes. Type 2 diabetes contributes to the development of heart failure through a variety of mechanisms, including disease-specific myocardial structural, functional and metabolic changes. This review will focus on the contemporary contributions of state of the art non-invasive technologies to our understanding of diabetic cardiomyopathy, including data on cardiac disease phenotype, cardiac energy metabolism and energetic deficiency, ectopic and visceral adiposity, diabetic liver disease, metabolic modulation strategies and cardiovascular outcomes with new classes of glucose-lowering therapies.

Background: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison with subjects with bioprosthetic surgical aortic valve replacement (SAVR). Methods: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, computed tomography angiography, and ¹⁸ F-sodium fluoride ( ¹⁸ F-NaF) positron emission tomography. Participants (n=47) were imaged once with ¹⁸ F-NaF positron emission tomography/computed tomography either at 1 month (n=9, 19%), 2 years (n=22, 47%), or 5 years (16, 34%) after valve implantation. Patients subsequently underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made with matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol. Results: In patients with TAVI, native aortic valves demonstrated ¹⁸ F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI ( r =0.36, P =0.023). ¹⁸ F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio, 1.3 [1.2–1.7] versus 1.3 [1.2–1.5], respectively; P =0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8%, respectively; P =0.78), computed tomography (15% versus 14%, respectively; P =0.87), and positron emission tomography (15% versus 29%, respectively; P =0.09). Baseline ¹⁸ F-NaF uptake was associated with a subsequent change in peak aortic velocity for both TAVI ( r =0.7, P <0.001) and SAVR ( r =0.7, P <0.001). On multivariable analysis, ¹⁸ F-NaF uptake was the only predictor of peak velocity progression ( P <0.001). Conclusions: In patients with TAVI, native aortic valves demonstrate evidence of ongoing active disease. Across imaging modalities, TAVI degeneration is of similar magnitude to bioprosthetic SAVR, suggesting comparable midterm durability. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02304276.