Recent Insights into Pharmacologic Cardiovascular Risk Reduction in Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) affects nearly 30 million Americans and carries an increased risk of macrovascular complications of myocardial infarction, stroke, and cardiovascular death. While aggressive cardiovascular risk factor reduction has long been advocated in patients with diabetes, clinical trials have only recently demonstrated that such reductions result in improved outcomes. This review discusses recent evidence for risk reduction strategies and therapies with a focus on the management of glycemia, dyslipidemia, and hypertension. Although the degree to which aggressive glycated hemoglobin reduction decreases the risk of macrovascular outcomes remains unclear, the use of specific agents, such as the newer sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) agonists, may reduce cardiovascular events in patients with diabetes, irrespective of glycated hemoglobin reduction. Statins have been the mainstay of dyslipidemia management, with recent guidelines recommending statin use in all patients aged 40-75 years with diabetes. There is an emerging role for the recently developed proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in diabetes, as these agents further reduce serum cholesterol and clinical cardiovascular events beyond the maximum tolerated statin therapy. Lastly, most evidence suggests that aggressive blood pressure lowering in diabetic patients with hypertension reduces macrovascular events. Recent studies have re-affirmed a goal blood pressure of 140/90, and a lower pressure is likely prudent in most patients with diabetes. Specifically, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) may reduce cardiovascular risk in patients with diabetes beyond their blood pressure-lowering effect. In conclusion, there is a growing literature which shows that the risk of cardiovascular outcomes can be reduced in most patients with diabetes, as outlined in this review.

Impact of atherosclerosis imaging-quantitative computed tomography on diagnostic certainty, downstream testing, coronary revascularization, and medical therapy: the CERTAIN study.

AIMS: The incremental impact of atherosclerosis imaging-quantitative computed tomography (AI-QCT) on diagnostic certainty and downstream patient management is not yet known. The aim of this study was to compare the clinical utility of the routine implementation of AI-QCT versus conventional visual coronary CT angiography (CCTA) interpretation. METHODS AND RESULTS: In this multi-centre cross-over study in 5 expert CCTA sites, 750 consecutive adult patients referred for CCTA were prospectively recruited. Blinded to the AI-QCT analysis, site physicians established patient diagnoses and plans for downstream non-invasive testing, coronary intervention, and medication management based on the conventional site assessment. Next, physicians were asked to repeat their assessments based upon AI-QCT results. The included patients had an age of 63.8 ± 12.2 years; 433 (57.7%) were male. Compared with the conventional site CCTA evaluation, AI-QCT analysis improved physician's confidence two- to five-fold at every step of the care pathway and was associated with change in diagnosis or management in the majority of patients (428; 57.1%; P < 0.001), including for measures such as Coronary Artery Disease-Reporting and Data System (CAD-RADS) (295; 39.3%; P < 0.001) and plaque burden (197; 26.3%; P < 0.001). After AI-QCT including ischaemia assessment, the need for downstream non-invasive and invasive testing was reduced by 37.1% (P < 0.001), compared with the conventional site CCTA evaluation. Incremental to the site CCTA evaluation alone, AI-QCT resulted in statin initiation/increase an aspirin initiation in an additional 28.1% (P < 0.001) and 23.0% (P < 0.001) of patients, respectively. CONCLUSION: The use of AI-QCT improves diagnostic certainty and may result in reduced downstream need for non-invasive testing and increased rates of preventive medical therapy.

Contribution of the left atrial remodeling to the elevated pulmonary capillary wedge pressure in patients with WHO Group II pulmonary hypertension.

BACKGROUND: The contribution of progressive left atrial (LA) enlargement to elevated pulmonary capillary wedge pressure (PCWP) in patients with WHO Group II pulmonary hypertension (PH) has not been well studied. We hypothesized that progressive LA enlargement is associated with increased PCWP. METHODS: A cross-sectional retrospective cohort consisted of 166 patients with HF and WHO Group II PH, confirmed by right heart catheterization (RHC). LA anteroposterior dimension and volume were measured on TTE. PCWP and other hemodynamic parameters were measured by RHC. Univariate and multivariate logistic regression models were used for analysis. RESULTS: LA enlargement was associated with advanced age, increased BMI, and LV ejection fraction < 40%. PCWP was progressively increased in patients with dilated LA: 16.9 ± 7.4 mmHg in normal LA, 17.6 ± 7.2 mmHg in mildly dilated LA, 22.6 ± 6.3 mmHg in moderately and 22 ± 7.6 in severely dilated LA (p < 0.001). In multiple logistic regression, after adjustment for echocardiographic and clinical variables, severe LA enlargement was independently predictive of elevated PCWP (OR 3.468; 95% CI 1.046-11.504; p = 0.042). After excluding significant mitral regurgitation, progressive LA dilatation was associated with higher PCWP V-wave amplitude: from 21.3 ± 10.4 mmHg in patients with normal LA size, to 30.9 ± 11.7 mmHg in moderately dilated and 31.0 ± 11.6 mmHg in severely dilated LA (p < 0.001). CONCLUSIONS: In patients with HF and WHO Group II PH, progressive LA enlargement was independently associated with elevated PCWP. After excluding significant mitral regurgitation, LA enlargement was also associated with increased V-wave amplitude, indicative of decreased atrial compliance.

Pulmonary tumour thrombotic microangiopathy as a cause of new-onset pulmonary hypertension in a patient with metastatic low-grade serous ovarian cancer.

A 78-year-old woman with metastatic low-grade serous ovarian cancer presented with rapidly progressive exertional dyspnoea and hypoxia, and was found to have new-onset severe pulmonary hypertension (PH) by right heart catheterisation. A diagnosis of pulmonary tumour thrombotic microangiopathy (PTTM) was made at autopsy. PTTM is a rare complication of advanced cancer that often presents as rapidly progressive PH or acute hypoxic respiratory failure. Widespread tumour cell emboli in the pulmonary arteries and arterioles are hypothesised to induce fibrocellular subintimal proliferation and microthrombi, leading to increased pulmonary vascular resistance and PH. PTTM arising from serous ovarian cancer is exceedingly rare, with only two previously reported cases. A discussion of the pathophysiology, diagnosis and management of PTTM is presented.