Kobina Wilmot

Mediterranean Dietary Patterns and Cardiovascular Health

The Mediterranean dietary pattern has been linked with reduced cardiovascular disease incidence and mortality. Components of the Mediterranean diet associated with better cardiovascular health include low consumption of meat and meat products, moderate consumption of ethanol (mostly from wine), and high consumption of vegetables, fruits, nuts, legumes, fish, and olive oil. Increasing evidence indicates that the synergy among these components results in beneficial changes in intermediate pathways of cardiometabolic risk, such as lipids, insulin sensitivity, oxidative stress, inflammation, and vasoreactivity. As a result, consumption of a Mediterranean dietary pattern favorably affects numerous cardiovascular disease risk factors, such as dyslipidemia, hypertension, metabolic syndrome, and diabetes. Moreover, strong evidence links this dietary pattern with reduced cardiovascular disease incidence, reoccurrence, and mortality. This review evaluates the current evidence behind the cardioprotective effects of a Mediterranean dietary pattern.

Prevalence of Resistant Hypertension and Eligibility for Catheter-Based Renal Denervation in Hypertensive Outpatients

BACKGROUND Studies of endovascular renal denervation (RDN) have demonstrated significant blood pressure reduction in eligible patients with resistant hypertension. These trials have used stringent inclusion and exclusion criteria in patient enrollment, potentially selecting for a small subset of patients with resistant hypertension. In this study, we examined the changes in estimated prevalence of resistant hypertension when using increasingly stringent definitions of resistant hypertension in a fixed population and assessed the generalizability of RDN when applying study criteria to a community-based hypertensive population. METHODS A retrospective chart review was done of hypertensive outpatients. Four increasingly stringent interpretations of the American Heart Association definition of resistant hypertension were used to calculate prevalence estimates. Patients eligible for RDN were identified using criteria from SYMPLICITY HTN-3. Demographic and clinical characteristics were compared. RESULTS We identified 1,756 hypertensive outpatients; 55.0% were male, 53.9% were white, and subjects had a mean age of 66.6 ± 12.5 years and a body mass index (BMI) of 30.1 ± 10.7 kg/m(2). Only 14 (0.8%) were eligible for RDN. Among these patients, 10 (71.4%) were female and all were black, with a mean age of 69.9 ± 8.8 and BMI of 35.7 ± 6.6. Congestive heart failure was more common in patients eligible for RDN. CONCLUSIONS Patients eligible for RDN based on published studies represent an exceedingly small proportion of the total hypertensive population. Further studies are necessary to determine if the benefits of RDN can be generalized to a broader range of hypertensive patients than those included in previous trials.

Sex Differences in Mental Stress‐Induced Myocardial Ischemia in Patients With Coronary Heart Disease

Background Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress‐induced myocardial ischemia (MSIMI). Methods and Results We studied 686 patients (191 women) with stable coronary heart disease (CHD). Patients underwent 99mTc‐sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more‐adverse psychosocial profile than men whereas there were few differences in medical history and CHD risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction, P<0.001) and the incidence of MSIMI was 82.6% higher (interaction, P=0.004) in women than in men. Incidence of MSIMI in women ≤50 years was almost 4‐fold higher than in men of similar age and older patients. These results persisted when adjusting for sociodemographic and medical risk factors, psychosocial factors, and medications. There were no significant sex differences in inducible ischemia with conventional stress. Conclusions Young women with stable CHD are susceptible to MSIMI, which could play a role in the prognosis of this group.

Statins in the Elderly: A Patient‐Focused Approach

Individuals age >65 years represent the fastest‐growing subpopulation in the United States. Although these individuals with the highest cardiovascular risk profile would be anticipated to be the most aggressively treated, paradoxically, treatment and baseline risk are inversely related. Presumably, the elderly population would benefit from high‐intensity statin therapy; however, as per the 2013 American College of Cardiology/American Heart Association guidelines, given the scarcity of evidence in patients age >75, there are only sufficient data from randomized controlled trials to support use of moderate‐intensity statin therapy for secondary prevention. Despite evidence demonstrating statins are beneficial in the elderly, the decision to initiate and sustain treatment should be a well‐informed and collaborative decision. One must balance the benefits (secondary atherosclerotic cardiovascular prevention, stroke reduction, decreased morbidity and mortality) with the potential risks to the elderly (altered metabolism, comorbidities, polypharmacy and drug‐drug interactions, side effects, cognitive limitations, and cost).

Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes

Rationale: Leukocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow–derived circulating progenitor cells are involved in tissue repair and regeneration. Objective: Main objective of this study was to examine the relationship between LTL and progenitor cells and their impact on adverse cardiovascular outcomes. Methods and Results: We measured LTL by quantitative polymerase chain reaction in 566 outpatients (age: 63±9 years; 76% men) with coronary artery disease. Circulating progenitor cells were enumerated by flow cytometry. After adjustment for age, sex, race, body mass index, smoking status, and previous myocardial infarction, a shorter LTL was associated with a lower CD34+ cell count: for each 10% shorter LTL, CD34+ levels were 5.2% lower (P<0.001). After adjustment for the aforementioned factors, both short LTL (<Q1) and low CD34+ levels (<Q1) predicted adverse cardiovascular outcomes (death, myocardial infarction, coronary revascularization, or cerebrovascular events) independently of each other, with a hazard ratio of 1.8 and 95% confidence interval of 1.1 to 2.0, and a hazard ratio of 2.1 and 95% confidence interval of 1.3 to 3.0, respectively, comparing Q1 to Q2–4. Patients who had both short LTL (<Q1) and low CD34+ cell count (<Q1) had the greatest risk of adverse outcomes (hazard ratio =3.5; 95% confidence interval, 1.7–7.1). Conclusions: Although shorter LTL is associated with decreased regenerative capacity, both LTL and circulating progenitor cell levels are independent and additive predictors of adverse cardiovascular outcomes in coronary artery disease patients. Our results suggest that both biological aging and reduced regenerative capacity contribute to cardiovascular events, independent of conventional risk factors.

The Mental Stress Ischemia Prognosis Study: Objectives, Study Design, and Prevalence of Inducible Ischemia

Objective Mental stress–induced myocardial ischemia (MSIMI) is a common phenomenon in patients with coronary artery disease (CAD), but contemporary studies of its prognostic significance and its underlying pathophysiology are limited. Methods We prospectively enrolled patients with confirmed CAD in the Mental Stress Ischemia Prognosis Study (MIPS) between 2011 and 2014. All patients underwent mental stress testing using a standardized public speaking task, and ischemia was detected by 99mTc-sestamibi myocardial perfusion imaging. Patients also underwent conventional stress testing for myocardial ischemia (CSIMI) using exercise or pharmacological stress testing. Furthermore, digital microvascular flow, endothelial function, arterial stiffness, and blood sample collections were performed before, during, and after mental stress. Two-year adverse clinical outcomes are being assessed. Results Six-hundred ninety-five patients completed baseline enrollment in the MIPS. Their mean (standard deviation) age was 62.9 (9.1) years, 72% were men, 30% were African American, and 32% had a history myocardial infarction. The prevalence of MSIMI and CSIMI is 16.1% and 34.7%, respectively. A total of 151 patients (22.9%) had only CSIMI, 28 (4.2%) had only MSIMI, and 78 (11.8%) had both MSIMI and CSIMI. Patients with ischemia had a lower ejection fraction and higher prevalence of previous coronary artery bypass grafting compared with those without inducible ischemia (p < .050). The prevalence of obstructive CAD was not statistically different between patients with and without MSIMI (p = .426); in contrast, it was higher in patients with CSIMI (p < .001). Conclusions The MIPS data will provide useful information to assess the prognostic significance and underlying mechanisms of MSIMI.

Mental Stress–Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction: Sex Differences and Mechanisms

Background: Mental stress-induced myocardial ischemia (MSIMI) is frequent in patients with coronary artery disease and is associated with worse prognosis. Young women with a previous myocardial infarction (MI), a group with unexplained higher mortality than men of comparable age, have shown elevated rates of MSIMI, but the mechanisms are unknown. Methods: We studied 306 patients (150 women and 156 men) ⩽61 years of age who were hospitalized for MI in the previous 8 months and 112 community controls (58 women and 54 men) frequency matched for sex and age to the patients with MI. Endothelium-dependent flow-mediated dilation and microvascular reactivity (reactive hyperemia index) were measured at rest and 30 minutes after mental stress. The digital vasomotor response to mental stress was assessed using peripheral arterial tonometry. Patients received 99mTc-sestamibi myocardial perfusion imaging at rest, with mental (speech task) and conventional (exercise/pharmacological) stress. Results: The mean age of the sample was 50 years (range, 22–61). In the MI group but not among controls, women had a more adverse socioeconomic and psychosocial profile than men. There were no sex differences in cardiovascular risk factors, and among patients with MI, clinical severity tended to be lower in women. Women in both groups showed a higher peripheral arterial tonometry ratio during mental stress but a lower reactive hyperemia index after mental stress, indicating enhanced microvascular dysfunction after stress. There were no sex differences in flow-mediated dilation changes with mental stress. The rate of MSIMI was twice as high in women as in men (22% versus 11%, P=0.009), and ischemia with conventional stress was similarly elevated (31% versus 16%, P=0.002). Psychosocial and clinical risk factors did not explain sex differences in inducible ischemia. Although vascular responses to mental stress (peripheral arterial tonometry ratio and reactive hyperemia index) also did not explain sex differences in MSIMI, they were predictive of MSIMI in women only. Conclusions: Young women after MI have a 2-fold likelihood of developing MSIMI compared with men and a similar increase in conventional stress ischemia. Microvascular dysfunction and peripheral vasoconstriction with mental stress are implicated in MSIMI among women but not among men, perhaps reflecting women’s proclivity toward ischemia because of microcirculatory abnormalities.

Hemodynamic, catecholamine, vasomotor and vascular responses: Determinants of myocardial ischemia during mental stress

AIMS Mental stress-induced myocardial ischemia (MSIMI) in patients with coronary artery disease (CAD) is associated with adverse cardiovascular outcomes. We aim to assess hemodynamic, neuro-hormonal, endothelial, vasomotor and vascular predictors of MSIMI. METHODS AND RESULTS We subjected 660 patients with stable CAD to 99mTc sestamibi myocardial perfusion imaging at rest, with mental (speech task) and with conventional (exercise/pharmacological) stress. Endothelium-dependent flow-mediated dilation (FMD), microvascular reactivity [reactive hyperemia index (RHI)] and arterial stiffness [pulse wave velocity (PWV)] were measured at rest and 30-min after mental stress. The digital microvascular vasomotor response during mental stress was assessed using peripheral arterial tonometry (PAT). A total of 106(16.1%) patients had MSIMI. Mental stress was accompanied by significant increases in rate-pressure-product (heart rate x systolic blood pressure; RPP), epinephrine levels and PWV, and significant decreases in FMD and PAT ratio denoting microvascular constriction. In comparison to those with no MSIMI, patients with MSIMI had higher hemodynamic and digital vasoconstrictive responses (p<0.05 for both), but did not differ in epinephrine, endothelial or macrovascular responses. Only presence of ischemia during conventional stress (OR of 7.1, 95%CI of 4.2, 11.9), high hemodynamic response (OR for RPP response≥vs<ROC cutoff of 1.8, 95%CI of 1.1, 2.8), and high digital vasoconstriction (OR for PAT ratio<vs≥ROC cutoff of 2.1, 95%CI of 1.3, 3.3) were independent predictors of MSIMI. CONCLUSION Ischemia during conventional stress testing and hemodynamic and vasoconstrictive responses to mental stress can help predict subjects with CAD at greater risk of developing MSIMI.

Sex Differences in Hemodynamic and Microvascular Mechanisms of Myocardial Ischemia Induced by Mental Stress

Objective— To investigate sex-specific vascular mechanisms for mental stress-induced myocardial ischemia (MSIMI). Approach and Results— Baseline data from a prospective cohort study of 678 patients with coronary artery disease underwent myocardial perfusion imaging before and during a public speaking stressor. The rate-pressure product response was calculated as the difference between the maximum value during the speech minus the minimum value during rest. Peripheral vasoconstriction by peripheral arterial tonometry was calculated as the ratio of pulse wave amplitude during the speech over the resting baseline; ratios <1 indicate a vasoconstrictive response. MSIMI was defined as percent of left ventricle that was ischemic and as a dichotomous variable. Men (but not women) with MSIMI had a higher rate-pressure product response than those without MSIMI (6500 versus 4800 mm Hg bpm), whereas women (but not men) with MSIMI had a significantly lower peripheral arterial tonometry ratio than those without MSIMI (0.5 versus 0.8). In adjusted linear regression, each 1000-U increase in rate-pressure product response was associated with 0.32% (95% confidence interval, 0.22–0.42) increase in inducible ischemia among men, whereas each 0.10-U decrease in peripheral arterial tonometry ratio was associated with 0.23% (95% confidence interval, 0.11–0.35) increase in inducible myocardial ischemia among women. Results were independent of conventional stress-induced myocardial ischemia. Conclusions— Women and men have distinct cardiovascular reactivity mechanisms for MSIMI. For women, stress-induced peripheral vasoconstriction with mental stress, and not increased hemodynamic workload, is associated with MSIMI, whereas for men, it is the opposite. Future studies should examine these pathways on long-term outcomes.

The association between acute mental stress and abnormal left atrial electrophysiology

Acute stress may trigger atrial fibrillation (AF), but the underlying mechanisms are unclear. We examined if acute mental stress results in abnormal left atrial electrophysiology as detected by more negative deflection of P‐wave terminal force in lead V1 (PTFV1), a well‐known marker of AF risk.