Migraine Throughout Women’s Reproductive Life: Unravelling the Cardiovascular and Metabolic Implications

Recognizing Pregnancy-Associated Cardiovascular Risk Factors

Sex Differences in Early Carotid Atherosclerosis (from the Community-Based Gutenberg-Heart Study)

Background: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction (MI) occurring most often in young women without cardiovascular disease (CVD) risk factors. SCAD is associated with fibromuscular dysplasia (FMD), pregnant/postpartum state, and extreme mental stress or physical exertion. Migraine headaches have been reported common in SCAD and may increase CVD risk. The objective was to assess differences in presentation, clinical factors, and outcomes in SCAD patients with migraines (M-SCAD) compared to those without, and determine M-SCAD prevalence. Methods: A retrospective cross-sectional observation study of patients with angiographically confirmed SCAD was conducted using the Mayo Clinic SCAD Registry. Participant-provided data and records were reviewed for migraine history, CVD risk factors, SCAD details, CVD and migraine therapies, and outcomes. Ordinal and nominal variables were compared using Pearson's chi squared test, and continuous variables were compared using Student's t-test. Statistical significance was set at p < 0.05. Results: Among 586 patients with complete questionnaires, 236 had a history of migraines; the lifetime and 1-year prevalence of migraines were 40% and 27% respectively. Migraines are more common in SCAD survivors than a comparable population (40% vs 33%, p=0.0002). M-SCAD patients were more likely to be female (99.6% vs 94%, p=0.001), have SCAD at a younger age (45.3 yrs. vs 47.6 yrs., p=0.004), and report a history of aneurysms (7.6% vs 1.7%, p=0.0004), 46% of which occurred in head or neck vessels. There was a trend toward increased head and neck FMD in M-SCAD (32% vs 23%, p=0.095). Prevalence of depression (27% vs 17%, p=0.005), anxiety (32% vs 24%, p=0.038), recurrent angina (62% vs 44%, p=<0.001) and concern for recurrent SCAD (46% vs 37%, p=0.034) were higher in M-SCAD. Triptans were stopped in 39% of migraineurs at the time of MI. Conclusion: As compared to SCAD survivors without migraines, those with M-SCAD are younger, more often report a history of depression, anxiety, and aneurysms, and have more chest pain after SCAD. Further investigation into this association and development of safe, effective treatments of both headache and angina after SCAD is needed.

Not all women diagnosed with PCOS share the same cardiovascular risk profiles

Background: Spontaneous coronary artery dissection (SCAD) causes acute coronary syndrome via the sudden separation between the coronary arterial wall layers and/or hematoma. The SCAD patient population is >80% female who typically have few or no traditional cardiovascular disease risk factors (e.g., obesity, hypertension). Risk of a recurrent SCAD is reported as high as 19% at 3 years after an initial SCAD. Mechanisms underlying SCAD (re)occurrence are unknown. Common triggers for SCAD include sympathoexcitatory stimuli, including heavy exercise and intense Valsalva-like activities. This study tested the hypothesis that SCAD patients exhibit greater neurocardiovascular responses (e.g., blood pressure, heart rate, muscle sympathetic nerve activity) to isometric handgrip and post-exercise ischemia compared to healthy females. Methods: Eight females with a history of SCAD (age: 56±6 yrs, BMI: 28±4 kg/m2) and 6 age- and BMI-matched healthy female controls (CON, age: 55±8 yrs, BMI: 26±5 kg/m2) participated. Continuous blood pressure (finger photoplethysmography) and heart rate (3-lead ECG) were measured during rest (1 minute), isometric handgrip at 30% maximal voluntary contraction (2 minutes), and post-exercise ischemia at 220 mmHg (2 minutes) to isolate the skeletal muscle metaboreflex. Muscle sympathetic nerve activity (MSNA, peroneal microneurography) was measured in a subset of participants (5 SCAD/4 CON). Data are presented as an absolute change from rest (mean±SD). Two-way independent t-tests were used for statistical analyses. Results: Resting mean blood pressure (SCAD: 96±8 vs CON: 91±9 mmHg, p=0.354), heart rate (SCAD: 56±11 vs CON: 59±10 bpm, p=0.666), and MSNA (SCAD: 50±19 vs CON: 43±32 bursts/100 heartbeats, p=0.697) were not different between groups. Relative to healthy controls, SCAD patients elicited greater increases in mean blood pressure during isometric handgrip (SCAD: Δ9±3 vs CON: Δ4±4 mmHg, p=0.034) and post-exercise ischemia (SCAD: Δ7±4 vs CON: Δ3±3 mmHg, p=0.046). There were no group differences regarding heart rate responses during isometric handgrip (SCAD: Δ3±4 vs CON: Δ4±4 bpm, p=0.359) and post-exercise ischemia (SCAD: Δ3±4 vs CON: Δ2±3 bpm, p=0.861). Responses in MSNA during isometric handgrip (SCAD: Δ12±8 vs CON: Δ9±8 bursts/100 heartbeats, p=0.536) and post-exercise ischemia (SCAD: Δ11±2 vs CON: Δ13±10 bursts/100 heartbeats, p=0.713) also were not different between groups. Conclusion: These preliminary data suggest that compared to healthy females, female patients who experienced a SCAD exhibit greater pressor, but not chronotropic or sympathetic, responses to isometric handgrip and post-exercise ischemia. Exaggerated pressor responses to these perturbations may be a potential risk factor for SCAD (re)occurrence. NIH K23 HL155506, NIH T32 DK07352, NIH K01 HL148144, NIH UL1 TR0022377, and AHA 898649. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Introduction: Poorly controlled hypertension causes damage to the retinal microcirculation, which is predictive and associated to risk of stroke. Studies have shown that retinal microvascular changes can be reliably documented by retinal photographs. This study aims at examine the associative risk and incident of hypertensive retinopathy related serious cardiovascular events in primary care. Methodology: This is a prospective cohort study involving hypertensive patients in one regional primary care clinic of Hong Kong. Eligible digital retinal photographs of hypertensive patients done in the period Jan 1, 2011 to Dec 31, 2012 were graded based on Wong & Mitchell criteria. Consecutive subjects with hypertensive retinopathy (HTR) and without HTR (Non-HTR) were allocated to cohort and control group respectively until ceiling of 138. All patients will be followed prospectively for five years to exam the incidence of serious cardiovascular events. The relative risk of hypertensive retinopathy related serious cardiovascular events were investigated. Results: The cohort group patients are younger (mean age 57.3 versus 61.0, P<0.01), and have higher proportion of comorbid hyperlipidaemia (P=0.02). There are no statistical difference in sex, smoking status, duration of hypertension (HT), number of anti-hypertensive medication taking and mean blood pressure. At five year, both groups have no cardiovascular related mortality. Cohort group has 13 events of cardiovascular disease (incidence rate 9.42%), while control group has 5 events (incidence rate 3.62%). The five year realative risk (RR) of HTR for serious cardiovascular events is 2.77 (95% CI: 0.96-7.98, P=0.051), while five year RR of HTR for stroke is 9.56 (95% CI 1.19-76.5, P=0.010). With logistic regression analyasis, HTR is independent risk factor for stroke, with RR 8.55 (p=0.047). Conclusion: Hypertensive retinopathy is the independent predictive risk factor for stroke. The sensitivity and specificity of HT patients with HTR in predicting stroke in 5 years is 90.0% and 51.5% respectively.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a disease that develops unrelated to intracoronary intervention, atherosclerosis, aortic dissection, or mechanical trauma and causes a false lumen (intramural hematoma) in the wall of the coronary artery (CA) with impaired blood flow in it and myocardial ischemia in the affected region of the CA. SCAD most often develops in young and middle-aged adults (aged ≤50 years); among women, it becomes the culprit in 24%–35% of cases of acute myocardial infarction (MI). SCAD is a risk factor for MI, and incorrect interpretation of the angiographic picture and intravascular imaging methods can lead to incorrect tactics of patient behavior.&#x0D; CLINICAL CASE DESCRIPTION: This article presents a clinical case of SCAD leading to the development of MI in a young woman with concomitant connective tissue dysplasia and hereditary thrombophilia. The angiographic disease course resembled focal atherosclerosis, and in the course of invasive management, complications had arisen, confirming the probable genesis of coronary artery obstruction.&#x0D; CONCLUSION: SCAD is a complex disease, with a sudden onset and an ambiguous prognosis. In most cases, SCAD develops in young women in the absence of cardiovascular factors. It is difficult to diagnose because its signs and symptoms are similar to more common diseases, mainly MI. SCAD can masquerade as focal stenosis on an angiogram, mimicking an atherosclerotic plaque. The «gold standard» for diagnosing SCAD is optical coherence tomography (OCT). OCT enables the visualization of the state of all coronary artery walls and elucidates the pathogenetic mechanisms of MI. If performing OCT is impossible after diagnostic coronary angiography in young patients in suspected cases, the likelihood of DST and SCAD risk must be assessed to avoid errors in choosing treatments. The technical accessibility of intracoronary imaging methods reduces the frequency of diagnostic and, consequently, treatment errors.

This editorial appraises an article in the current issue of Hypertension that examines the prospective relationships between features of the metabolic syndrome (MetS) and early death in a population-based cohort form Northern Italy.1 We also discuss, in light of that study’s findings, how relevant conventional definitions of the MetS are for identifying individuals at high risk of early death. The MetS describes a constellation of metabolic and cardiovascular disease risk factors. Although varying definitions of the MetS exist, all of the commonly used definitions include a measure of obesity, hyperglycemia, hypertension, and dyslipidemia.2–4 These definitions are based on “expert” opinion and not on evidence derived from prospective studies, which would be preferable. Thus, it remains uncertain whether the component features of the MetS or the thresholds at which each component is defined as present or absent are informative and optimal for predicting risk of disease or early death. It is also undetermined whether MetS represents a distinct pathophysiological entity. Notwithstanding these issues, the syndrome is extensively used in research studies, and many advocate its use in clinical practice5 to identify people at high risk of cardiovascular disease and early death. The idea that cardiovascular risk factors with a common etiology cluster in certain individuals at high risk of cardiovascular disease was first popularized by Reaven6 in the 1980s, although the origins of the MetS date back much earlier.7 Reaven’s6 emphasis was on elucidating the underlying pathophysiology of cardiovascular disease, for which he postulated that insulin resistance plays a pivotal role, and not on developing a diagnosis of MetS, which could be used in clinical practice. Superficially, at least, MetS relates strongly with cardiovascular morbidity and early death8; this is perhaps unsurprising, because so too do each of the component features of the …

Background The metabolic syndrome (MS) is a clustering of cardiovascular (CV) risk factors and is noted to be increasing globally. Several studies have shown a link between the MS, chronic kidney disease (CKD) and end-stage renal disease (ESRD) possibly through a process of inflammation. Dialysis therapy may increase inflammation and could worsen MS and increase CV risk and diseases in ESRD patients. ESRD has been associated with increased CV disease in dialysis patients. Although there have been several reports on the prevalence of MS from the general population as well as from other specific groups, there are no known studies in South Africa on the prevalence of MS in ESRD patients on chronic dialysis therapy. The prevalence and risk factors for CV diseases are also currently unknown in the dialysis population in Cape Town. Aim The aim of this study was to determine the prevalence of MS in the dialysis population at Groote Schuur Hospital in Cape Town, to determine the effect of dialysis on MS and its traits and to evaluate CV risk in this patient group. Methods A total of 143 prevalent chronic dialysis patients who consented were used for this study. Demographic and relevant clinical details including systolic and diastolic blood pressures, waist and hip circumference and body mass index were obtained from all patients. Blood was drawn in the fasting state for assessment of full lipogram, glucose, ferritin, iron, calcium and phosphate. The metabolic syndrome was defined using the Adult Treatment Panel III (ATPIII) criteria. To determine the impact of dialysis on MS and its traits in our patients, only incident (new) patients starting dialysis were followed up for assessment of MS traits at timed intervals (at baseline, at 6 months and at 12 months) following initiation of chronic dialysis. To evaluate CV risk in this study, common traditional CV risk factors were assessed and were stratified according to number of risk factors as low ( ≤ 1), moderate (2 – 4) or high ( ≥ 4). Relevant statistical methods were used for analysis. Results Of the 143 patients in the study, 67.8% were on haemodialysis (HD) and 32.2% were on peritoneal dialysis (PD). The mean age of all the patients was 38.5 ± 10.4 years. The MS was present in 37.1% of all patients (PD – 52.2%, HD 29.9%; p = 0.015) and the frequency of increased waist circumference and hypertriglyceridaemia were significantly higher in PD patients than HD patients (p &lt; 0.0001 and p = 0.006 respectively). Hypertension was the most prevalent MS trait in all the patients (89.5%) and was also the most prevalent trait in males (92.4%), females (85.9%) and in HD and PD patients (91.3% and 88.7% respectively). The frequency of CV risk was 3.5, 75.5 and 21.0% respectively for low, moderate and high CV risk and there was no difference in CV risk in HD and PD patients. High CV risk correlated with body mass index (BMI), increased waist circumference (WC), hyperphosphataemia, raised calcium – phosphate product, raised parathyroid hormone (PTH) and elevated C-reactive protein (p &lt; 0.05). There was no significant change in MS prevalence or prevalence of MS traits in patients who were followed up irrespective of gender or modality of dialysis (p &gt; 0.05) Conclusion The prevalence of the MS is higher in dialysis patients compared to the general population in South Africa and among dialysis patients, the prevalence is higher in PD than HD patients. Patients with MS have significantly higher CV risk factors than those without MS. Although dialysis therapy appear to have no significant effects on the prevalence of the MS or its traits in this study, the increased prevalence of the MS and CV risk factors may be related to the underlying disease process associated with ESRD. There is therefore an urgent need to identify and treat dialysis patients with the MS in order to reduce CV morbidity and mortality in this group of patients. Further prolonged prospective studies are needed to clarify the impact of dialysis on the MS and its traits in the ESRD population.

Despite recent advancements in the recognition and diagnosis of spontaneous coronary artery dissection (SCAD), pathophysiologic mechanisms, predisposing and precipitating factors, risk of recurrences remain poorly understood and evidence-based treatment strategies are still unavailable. The goals of the study are to assess the characteristics of SCAD patients highlighting the predisposing and precipitating factors, to analyse the therapeutic management in the acute phase, to evaluate the incidence of SCAD recurrence and cardiovascular events during the follow-up and to assess the factors influencing the quality of life of patients after a SCAD event. We also aim to introduce our experience about the use of intra-aortic balloon pump in acute SCAD setting in order to support the percutaneous coronary intervention (PCI) or its use as part of a conservative management. We performed a retrospective, single-center, observational cohort study of patients with non-atherosclerotic, non-iatrogenic SCAD presenting to our Cath Lab in Santa Maria Annunziata Hospital (Bagno a Ripoli, Florence, Italy) with acute coronary syndrome (ACS). We enrolled 84 patients who presented with acute coronary syndrome and SCAD documented by coronary angiography or intracoronary imaging, from January 2015 to December 2024. We excluded patients with iatrogenic dissection and coronary atherosclerotic disease. Mean age was 56.2 ± 11.6 years and 79 (94%) patients were women. At baseline, 40% had hypertension, 38.8% dyslipidaemia, 29.4% was current smoker, only 2.4% had diabetes mellitus. The most frequent hospital presentation was NSTEMI (70,6%), followed by STEMI (28,2%) and ventricular tachycardia or ventricular fibrillation (3.5%). Majority of SCAD involved a single coronary artery territory (89.3%), and the most common coronary artery dissected was the left anterior descending artery and its branches (40.5%). Majority of patients (82%) were treated conservatively as initial strategy; 15 patients (18%) underwent myocardial revascularization with PCI or coronary artery bypass grafting (CABG). In nine cases (10.6%) IABP was implanted to perform a protect PCI (4.8%), as bridge to emergency CABG in course of hemodynamic instability (2.4%) or as part of conservative management (3.6%) avoiding coronary instrumentation and PCI with positive long-term outcome. During the follow-up period (median follow-up 2.6 years with interquartile range 1.1-5.4 years) the primary endpoint, defined as major adverse cardiovascular events (MACE) incidence and new onset or recurrence of atrial fibrillation (AF), occurred in 18 patients (21.4%). Hypertension emerged as independent predictor of primary outcome (p 0.001, HR 7.965) and low-dosage aspirin at discharge appeared to be protective reducing risk of primary outcome (p < 0.001, HR 0.0034). The secondary outcome was to evaluate quality of life (QoL) of patients who suffered SCAD using EQ-5D-5L questionnaire and Seattle Angina Questionnaire-7. No significative differences emerged between patients treated by PCI and patients treated conservatively. In SCAD patients, hypertension increases risk of primary outcome while low-dosage aspirin reduces risk during follow-up period. In terms of quality of life and post-SCAD chest pain, no significative differences emerged between patients treated by PCI and patients treated conservatively.

Nonalcoholic Fatty Liver Disease and Cardiovascular Disease Risk

Prevention of menstrual migraine with perimenstrual transdermal 17-β-estradiol: a randomized, placebo-controlled, double-blind crossover study

Case presentation: A 36-year-old nonsmoking, normotensive South Asian man presented to the emergency department of a community hospital with retrosternal chest pain of &60 minutes’ duration. His 12-lead ECG demonstrated 10 mm of ST-segment elevation in leads V2 through V6, and he received fibrinolytic therapy within 90 minutes of symptom onset. His pain resolved, but his ST segments only partially normalized; he had a peak creatine kinase of 4564 IU/L, and he showed signs of early heart failure. LDL cholesterol was 135 mg/dL, HDL 32 mg/dL, triglycerides 20 mg/dL, and total cholesterol 206 mg/dL; his body mass index (BMI) was 24 kg/m2. Cardiac catheterization demonstrated severe and diffuse triple-vessel disease, including occlusion of the proximal left anterior descending artery, as well as moderate left ventricular dysfunction. While in the hospital, he was diagnosed with new-onset type 2 diabetes mellitus and subsequently underwent uncomplicated coronary bypass surgery. South Asians are individuals whose ethnic roots originate from the Indian subcontinent, a large geographic area that includes India, Pakistan, Sri Lanka, Nepal, and Bangladesh. Collectively, South Asians represent one fifth of the global population. In North America, more than 2 million South Asians reside in the United States and almost 1 million in Canada. It is important to recognize that the term “South Asian” refers to a heterogeneous population, with important differences in diet, culture, and lifestyle among different South Asian populations and religions. Multiple studies of migrant South Asian populations have, however, confirmed a 3- to 5-fold increase in the risk for myocardial infarction and cardiovascular death as compared with other ethnic groups.1–3 In an analysis of age-standardized coronary heart disease (CHD) mortality in Canada over a 15-year period, South Asians had the highest CHD mortality compared with individuals of Chinese and European descent.4 In …

Osteoprotegerin (OPG), a member of the tumour necrosis factor receptor (TNFR) superfamily of proteins known to be involved in a large number of biological systems, plays a pivotal role in bone remodelling. In addition to the roles of OPG in bone metabolism, it has been reported to be associated with a high cardiovascular risk in patients with metabolic syndrome. In most cases, the exact functions of OPG remain to be established; however, the widespread expression of OPG suggests that this molecule may have multiple biological activities, mainly in the cardiometabolic environment. The aim of this study was to evaluate the value of OPG as a predictive marker for cardiovascular and metabolic risk in osteoporotic patients. The study group comprised patients with osteoporosis, in order to evaluate the association between OPG serum levels and cardiovascular pathology. Our results revealed significant correlations between classical biochemical bone and metabolic parameters, such as osteocalcin and parathyroid hormone with lipid and glucose biomarkers, sustaining the crosstalk between calcium and bone parameters and cardiovascular risk. The OPG serum level proved to have a significant and independent predictive value for metabolic syndrome (MetS) as a cardiovascular risk standard in osteoporotic patients. The OPG serum levels were increased in patients with MetS as a protective response against the atherosclerotic lesions. The serum levels of 25-hydroxy vitamin D had significant and independent predictive value for cardiovascular and metabolic risk in our subjects, sustaining the active role of vitamin D beyond the area of bone metabolism.

Background There is increasing evidence that patients with spontaneous coronary artery dissection (SCAD) have an underlying genetic susceptibility (Goel et al JAMA Intern Med175:821–826, 2015). Moreover, in a collaborative study involving 1,055 SCAD cases and 7,190 controls, we recently reported the first risk allele for SCAD, a variant (rs9349379-A) in the PHACTR1/EDN1 genetic locus (Adlam et al J Amer Coll Cardiol73:58–66, 2019). Purpose We sought to determine the clinical characteristics and initial genetic data for 11 families, in which more than one member has had an episode of SCAD. Methods Participants were recruited largely via a social media platform. Informed consent was obtained in all cases for analysis of genetic information using whole genome sequencing, as well as collection of clinical information. SCAD was confirmed by review of coronary angiogram images and clinical data collected by phone interview, as well as review of specialist letters and hospital records. Results Of 235 participants recruited to date, 23 cases showed familial clustering involving sister-sister pairs in six families, three first-degree cousins in one family (picture), two first-degree cousins in two families, a mother-son pair, and a family with concordant monozygotic twins, that is both twins having had SCAD. In an additional family, SCAD is discordant in monozygotic twins. A comparison of symptoms, age at SCAD, clinical syndrome, cardiovascular risk factors, SCAD risk factors, environmental triggers, SCAD location, acute management, left ventricular function and recurrent SCAD events in these families versus isolated cases, will be presented. Three sister-sister pairs have undergone whole genome sequencing and these data sets are undergoing segregation analysis to identify rare variants that are present exclusively in affected family members. Family E Pedigree. Shaded circles represent first cousins affected with SCAD. The top number represents age (in years) of the SCAD event and the bottom number represents current age (in years). Conclusions To our knowledge, this is the largest assembly of SCAD cases with familial clustering reported to date. It provides strong evidence supporting an underlying genetic basis for SCAD, which most likely is a multi-genic disorder that also involves important gene-environment interactions.