Long-term Risk Of Cardiovascular Disease Research Articles

Exaggerated Blood Pressure Response to Exercise Is a Risk of Future Hypertension Even in Healthy, Normotensive Young Individuals—Potential Preventive Strategies for This Phenomenon?

Physical activity and regular exercise are well known to reduce the risks of cerebrovascular and cardiovascular diseases, leading the American College of Sports Medicine to endorse the concept that “exercise is medicine”. However, a single bout of exercise temporarily raises arterial blood pressure (BP) to meet the metabolic demands of working muscle, and this BP response is particularly exaggerated in older adults and patients with cardiovascular conditions, such as hypertension, resulting in an exaggerated BP response during exercise. This presents a paradox: while regular exercise is crucial for preventing these diseases, excessively high BP responses during exercise could increase the risk of vascular damage. The mechanisms underlying this exaggerated BP response during exercise remain unclear, and effective exercise regimens for these populations have yet to be established. Currently, low-intensity exercise is recommended; however, its efficacy in disease prevention is uncertain. Notably, even among healthy individuals, there is significant variation in the BP response to exercise. Some healthy individuals, despite having normal resting BP, exhibit an exaggerated BP response during physical activity. Importantly, these individuals are often unaware that their BP becomes excessively elevated during physical activity. Repeated exposure to these heightened BP responses through regular physical activity may increase their long-term risk of cardiovascular disease. How can we prevent disease development in these individuals while still ensuring the effectiveness of exercise? Some studies have shown that individuals with a family history of hypertension may experience this phenomenon even in children and adolescents. Additionally, left ventricular hypertrophy contributes to an exaggerated BP response to exercise, suggesting a possible genetic influence. Conversely, other reports indicate that factors such as arterial stiffness, obesity, and low exercise capacity also contribute to this exaggerated response. Our recent preliminary data suggest that the cognitive benefits of exercise may be diminished in individuals who exhibit an exaggerated BP response during exercise. This implies that individuals with an exaggerated BP response, despite having normal resting BP, may not fully benefit from exercise. In this perspective paper, we review the physiological aspects of this phenomenon and explore strategies to address it. Additionally, we discuss BP responses in athletes within this content. Our goal is to prevent disease while maximizing the benefits of exercise for healthy individuals with an exaggerated BP response, as well as for elderly and cardiovascular patients.

Long-term association of remnant cholesterol with all-cause and cardiovascular disease mortality: a nationally representative cohort study.

Despite reducing low-density lipoprotein cholesterol (LDL-C) to the normal range, residual cardiovascular risk remain. Remnant cholesterol (RC) exerts a potential residual risk for cardiovascular disease (CVD) prevention, and the long-term longitudinal association between RC and mortality has yet to be well elucidated. This study examined a nationally representative sample of 13,383 adults aged 20 years or older (mean age 45.7 and 52% women) who participated in the NHANES III (from1988 to1994). Causes of death were ascertained by linkage to death records through December 31, 2019. The relations of RC with all-cause and CVD mortality were tested using weighted Cox proportional hazard models. Through a median follow-up of 26.6 years, 5,044 deaths were reported, comprising 1,741 deaths of CVD [1,409 deaths of ischemic heart disease (IHD) and 332 deaths of stroke] and 1,126 of cancer. Compared to those with RC <14.26 mg/dl (lowest quartile), participants with RC ≥29.80 mg/dl (highest quartile) had multivariable-adjusted HRs of 1.23 (95% CI: 1.07-1.42) for all-cause mortality, 1.22 (95% CI: 0.97-1.53) for CVD mortality, and 1.32 (95% CI: 1.03-1.69) for IHD mortality, and 0.89 (95% CI: 0.55-1.43) for stroke mortality, and 1.17 (95% CI 0.90-1.52) for cancer mortality. We observed that elevated RC levels increased CVD risk and IHD mortality despite LDL-C being in the normal range. Elevated blood RC was associated with an increased long-term risk of all-cause, CVD, and IHD mortality. These associations were independent of socioeconomic factors, lifestyles, and history of diseases, and remained robust across the LDL-C stratum. Measuring RC levels might favor clinical assessment of early CVD risk. Further investigation is needed to elucidate the optimal range of RC levels for cardiovascular disease health in the general population.

Cardiovascular Risk Factor Management After Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy (HDP) are associated with significantly increased risk of developing future cardiovascular disease (CVD). Obstetricians play a crucial role in CVD prevention for postpartum women and birthing people with HDP because they are primarily responsible for immediate postpartum management and can assist with care transitions to other health care practitioners for long-term management of CVD risk factors. Standardized calculators can be used to evaluate long-term CVD risk, which can help guide intensity of treatment. Emerging technologies such as remote blood pressure monitoring demonstrate promise for improving outcomes among patients with HDP. After HDP, all patients should be advised of their increased CVD risk. A plan should be made to initiate lifestyle modifications and antihypertensive therapy to achieve optimal blood pressure control with a target of lower than 130/80 mm Hg, assess lipids within 2-3 years of delivery, and evaluate for development of type 2 diabetes. Other CVD risk factors such as nicotine use should similarly be identified and addressed. In this review, we summarize the essential components of managing CVD risk after a pregnancy complicated by HDP, including blood pressure monitoring, risk stratification tools, and evidence-based lifestyle recommendations.

Chest Symptoms and Long-Term Risk of Incident Cardiovascular Disease

BackgroundWe sought to evaluate the associations of chest pain and dyspnea with the long-term risk of cardiovascular disease including coronary disease, heart failure, atrial fibrillation, and stroke. MethodsIn 13,200 participants without cardiovascular disease in the Atherosclerosis Risk in Communities study (1987-1989), chest pain was categorized into definite angina, possible angina, non-anginal chest pain, and no chest pain using the Rose questionnaire. Dyspnea was categorized into grades 3-4, 2, 1, and 0 by the modified Medical Research Council scale. The associations of chest pain and dyspnea with incident myocardial infarction, heart failure, atrial fibrillation, and stroke over a median follow-up of ∼27 years were quantified with multivariable Cox models. ResultsDefinite angina and possible angina were associated with myocardial infarction (adjusted hazard ratios [HR] 1.80 [95%CI 1.45-2.13] and 1.65 [1.27-2.15]). Although lesser magnitude than myocardial infarction, both definite and possible angina were associated with heart failure. For atrial fibrillation, possible angina showed higher HR than definite angina. Dyspnea showed similar HRs for myocardial infarction and heart failure in grades 3-4 (2.00 [1.61-2.49] and 1.94 [1.62-2.32]). Stroke was least associated with chest symptoms. Chest pain and dyspnea significantly improved the discrimination of cardiovascular disease except stroke, beyond traditional risk factors. ConclusionsIn individuals without cardiovascular disease, chest pain and dyspnea were independently associated with incident cardiovascular disease for about 3 decades, suggesting the need for evaluating chest pain from a broader perspective of cardiovascular disease beyond coronary disease and the importance of dyspnea for cardiovascular risk assessment including myocardial infarction.

Advanced cardiovascular physiology in an individual with type 1 diabetes after 10-year ketogenic diet.

Adults with type 1 diabetes (T1D) have an elevated risk for cardiovascular disease (CVD) compared with the general population. HbA1c is the primary modifiable risk factor for CVD in T1D. Fewer than 1% of patients achieve euglycemia (<5.7% HbA1c). Ketogenic diets (KD; ≤50 g carbohydrate/day) may improve glycemia and downstream vascular dysfunction in T1D by reducing HbA1c and insulin load. However, there are concerns regarding the long-term CVD risk from a KD. Therefore, we compared data collected in a 60-day window in an adult with T1D on exogenous insulin who consumed a KD for 10 years versus normative values in those with T1D (T1D norms). The participant achieved euglycemia with an HbA1c of 5.5%, mean glucose of 98 [5] mg/dL (median [interquartile range]), 90 [11]% time-in-range 70-180 mg/dL (T1D norms: 1st percentile for all), and low insulin requirements of 0.38 ± 0.03 IU/kg/day (T1D norms: 8th percentile). Seated systolic blood pressure (SBP) was 113 mmHg (T1D norms: 18th percentile), while ambulatory awake SBP was 132 ± 15 mmHg (T1D target: <130 mmHg), blood triglycerides were 69 mg/dL (T1D norms: 34th percentile), low-density lipoprotein was 129 mg/dL (T1D norms: 60th percentile), heart rate was 56 beats/min (T1D norms: >1SD below the mean), carotid-femoral pulse wave velocity was 7.17 m/s (T1D norms: lowest quartile of risk), flow-mediated dilation was 12.8% (T1D norms: >1SD above mean), and cardiac vagal baroreflex gain was 23.5 ms/mmHg (T1D norms: >1SD above mean). Finally, there was no indication of left ventricular diastolic dysfunction from echocardiography. Overall, these data demonstrate below-average CVD risk relative to T1D norms despite concerns regarding the long-term impact of a KD on CVD risk.NEW & NOTEWORTHY Adults with type 1 diabetes (T1D) have a 10-fold higher risk for cardiovascular disease (CVD) compared with the general population. We assessed cardiovascular health metrics in an adult with T1D who presented with a euglycemic HbA1c after following a ketogenic diet for the past 10 years. Despite concerns about the ketogenic diet increasing CVD risk, the participant exhibited below-average CVD risk relative to others with T1D when considering all outcomes together.

Long-term blood pressure variability and risk of cardiovascular diseases in populations with different blood pressure status: an ambispective cohort study.

We aimed to investigate the correlation between long-term blood pressure variability (BPV) and the risk of cardiovascular diseases (CVDs) among population with different blood pressure statuses (normotension, well-controlled hypertension, and uncontrolled hypertension). In this ambispective cohort study, CVD-free residents aged over 50 years were consecutively enrolled from two community health service centers (CHCs) in Tianjin, China from April 2017 to May 2017. Information on blood pressure was retrospectively extracted from electronic medical records of CHCs between January 2010 and May 2017, and the occurrence of new-onset CVDs was prospectively observed during follow-up until September 2019. Long-term variation of SBP and DBP was assessed using four indicators: SD, coefficient of variation (CV), average successive variability (ASV), and average real variability (ARV). Cox proportional hazards regression model was developed to identify the potential impact of BPV on the incidence of CVDs. The receiver operating characteristic curve (ROC) was utilized to evaluate the predictive value of BPV indicators for the occurrence of CVDs. Of 1275 participants included, 412 (32.3%) experienced new CVD events during the median 7.7 years of follow-up, with an incidence density of 499/10 000 person-year in the whole cohort. Cox regression analysis revealed that almost all SBP and DBP variability indicators (except for SBP-SD) were significantly related to the risk of CVDs, especially among individuals with well-controlled hypertension. A trend toward an increased risk of CVDs across BPV quartiles was also observed. Moderate predictive abilities of BPV were observed, with the area under ROC curves ranging between 0.649 and 0.736. For SBP variability, SD had the lowest predictive ability, whereas for DBP variability, ARV had the lowest predictive ability. No significant association of CVDs with SBP-SD was found in all analyses, no matter as a continuous or categorical variable. Elevated long-term BPV is associated with an increased risk of CVDs, especially among individuals with well-controlled hypertension. CV and ASV had higher predictive values than SD and ARV.

Perinatal depression and risk of maternal cardiovascular disease: a Swedish nationwide study.

Increasing evidence suggests that some reproductive factors/hazards are associated with a future risk of cardiovascular disease (CVD) in women. While major (non-perinatal) depression has consistently been associated with CVD, the long-term risk of CVD after perinatal depression (PND) is largely unknown. A nationwide population-based matched cohort study involving 55 539 women diagnosed with PND during 2001-14 in Sweden and 545 567 unaffected women individually matched on age and year of conception/delivery was conducted. All women were followed up to 2020. Perinatal depression and CVD were identified from Swedish national health registers. Using multivariable Cox models, hazard ratios (HR) of any and type-specific CVD according to PND were estimated. The mean age at the PND diagnosis was 30.8 [standard deviation (SD) 5.6] years. During the follow-up of up to 20 years (mean 10.4, SD 3.6), 3533 (6.4%) women with PND (expected number 2077) and 20 202 (3.7%) unaffected women developed CVD. Compared with matched unaffected women, women with PND had a 36% higher risk of developing CVD [adjusted HR = 1.36, 95% confidence interval (CI): 1.31-1.42], while compared with their sisters, women with PND had a 20% higher risk of CVD (adjusted HR = 1.20, 95% CI 1.07-1.34). The results were most pronounced in women without a history of psychiatric disorder (P for interaction < .001). The association was observed for all CVD subtypes, with the highest HR in the case of hypertensive disease (HR = 1.50, 95% CI: 1.41-1.60), ischaemic heart disease (HR = 1.37, 95% CI: 1.13-1.65), and heart failure (HR 1.36, 95% CI: 1.06-1.74). Women with PND are at higher risk of CVD in middle adulthood. Reproductive history, including PND, should be considered in CVD risk assessments of women.

Acute cardiac complications in colorectal cancer compared to other gastrointestinal malignancies: A 10-year retrospective study.

e15652 Background: Patients diagnosed with gastrointestinal (GI) cancers have long-term risks of cardiovascular disease and mortality. However, research comparing patients with colorectal cancer (CRC) to other GI cancers to assess their risk of acute cardiac complications is lacking. We evaluated the risk of hospitalization with acute cardiac complications (acute myocardial infarction [MI], arrhythmias and heart failure [HF]) among patients with CRC versus other GI cancers. Methods: A ten-year retrospective study using the Nationwide Inpatient Sample (NIS) database (2010-2019) was conducted. Using ICD-9 and ICD-10 codes, patients with diagnoses of GI cancers were identified. Multivariate logistic regression analysis was used to evaluate the odds of admission with an acute cardiac complication among patients with a diagnosis of CRC when compared to other GI cancers (esophageal, gastric, intestinal, hepatobiliary, and pancreatic cancers). Results: Among 4,408,321 GI cancer hospitalizations, 82,592 (0.18%) were for acute cardiac complications. Of these, 43.1% were in CRC patients and 56.9% were in those with other GI malignancies (P &lt; 0.001). Multivariate analyses revealed that patients with CRC had more than two-fold higher odds of acute MI compared to other GI cancer patients (Adjusted Odds Ratio (AOR): 2.47; 95% Confidence interval ( CI): 2.30-2.65), 1.8 times higher risk of arrhythmia (AOR: 1.78; 95% CI: 1.69-1.87) and 2.2 times higher risk of HF (AOR: 2.23; 95% CI:2.11-2.36). Overall, in comparison to other GI cancers, CRC patients were twice as likely to be admitted for acute cardiac complications (AOR: 2.09; 95% CI:2.02-2.16). Conclusions: Colorectal cancer patients have significantly higher odds of hospitalizations with acute cardiac complications relative to other GI malignancies. Older age and pre-existing comorbidities of CRC patients are unlikely to sufficiently explain these findings. CRC patients would benefit from active surveillance for cardiac diseases as well as further research on the long-term survival impact of acute cardiac complications on CRC patients. [Table: see text]

Long-term risk of cardiovascular disease associated with MASLD and different cardiometabolic risk factors in IBD patients: A prospective cohort study.

To examine the cardiovascular disease (CVD) risks associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and different numbers of cardiometabolic risk factors (CMRFs) in patients with inflammatory bowel disease (IBD) based on a long-term prospective cohort. Prevalent IBD patients at baseline who were free of CVD, cancer, alcoholic liver disease, cancer and hepatitis B/C virus seropositive were included (N = 4204). MASLD, MASLD subtypes [pure MASLD, MASLD with increased alcohol intake (MetALD)], lean/non-lean MASLD and CMRFs at baseline were defined according to the latest criteria proposed by AASLD and EASL. The primary outcome was incident CVD, including ischaemic heart disease (IHD), heart failure (HF) and stroke. Multivariable Cox proportional hazard models were used to estimate the relationship. Overall, 1528 (36.4%) were diagnosed with MASLD at baseline. During a median of 13.1-year follow-up, 503 incident CVDs were identified. Compared with IBD-only, IBD-MASLD patients had an increased risk of CVD (HR = 1.77, 95%CI: 1.26-2.49), especially in those with MetALD (HR = 2.34, 1.34-4.11) and lean MASLD (HR = 2.30, 1.13-4.66). As the number of CMRFs increased, the risks of CVD were significantly increased (ptrend <0.001), with a 116% and 92% excess risk in MASLD with 3 CMRFs (HR = 2.16, 1.48-3.15) and ≥4 CMRFs (HR = 1.92, 1.27-2.91). Similar excess risk of incident IHD and HF was observed in IBD-MASLD, either pure MASLD or MetALD, as well as lean/non-lean MASLD. MASLD is associated with increased CVD risk in IBD patients, with greater risk as number of CMRFs increased and evidently higher risk in MetALD and lean MASLD patients.

Potato Consumption and All-Cause and Cardiovascular Disease Mortality – A Long-Term Follow-Up of a Norwegian Cohort

BackgroundPotatoes are a staple food in many traditional cuisines, yet their impact on long-term risk of cardiovascular disease (CVD) and mortality is unclear, hampering evidence-based dietary guidelines. ObjectivesThis study aimed to examine the association between potato consumption and all-cause and CVD-specific death over a substantial follow-up period within a cohort predominantly consuming boiled potatoes. MethodsAdults from 3 Norwegian counties were invited to 3 health screenings in 1974–1988 (>80% attendance). Dietary data were collected using semiquantitative food frequency questionnaires at each screening to categorize weekly potato consumption (≤6, 7–13, or ≥14 potatoes/wk) and calculate daily cumulative mean intakes (grams/day). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression to estimate HRs and 95% CIs for the association between potato consumption and risk of death from all causes, CVD, ischemic heart disease (IHD), and acute myocardial infarction (AMI). ResultsAmong 77,297 participants with a mean baseline age of 41.1 y (range: 18.0–63.9 y), we observed 27,848 deaths, including 9072 deaths due to CVD, over a median follow-up of 33.5 y. Participants who consumed ≥14 potatoes/wk had a lower risk of all-cause death compared with those consuming ≤6 potatoes/wk (HR: 0.88; 95% CI: 0.84, 0.93). Potato consumption was associated with a minor, inverse risk of death due to CVD, IHD, and AMI. In continuous analyses of cumulative intakes, each 100 g/d increment was associated with 4% lower risk of death from all causes (HR: 0.96; 95% CI: 0.94, 0.98), CVD (HR: 0.96; 95% CI: 0.93, 0.99), IHD (HR: 0.96; 95% CI: 0.91, 1.00), and AMI (HR: 0.96, 95% CI: 0.91, 1.01). ConclusionsIn this cohort with a generally high consumption of predominantly boiled potatoes, we find modest, inverse associations between potato consumption and death from all causes, CVD, and IHD.

Cardiovascular outcomes in patients with homozygous familial hypercholesterolaemia on lipoprotein apheresis initiated during childhood: long-term follow-up of an international cohort from two registries

Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disease characterised by extremely high plasma LDL cholesterol from birth, causing atherosclerotic cardiovascular disease at a young age. Lipoprotein apheresis in combination with lipid-lowering drugs effectively reduce LDL cholesterol, but long-term health outcomes of such treatment are unknown. We aimed to investigate the long-term cardiovascular outcomes associated with lipoprotein apheresis initiated in childhood or adolescence. In this cohort study, data were drawn from the HoFH International Clinical Collaboration (HICC) and the international registry for Children with Homozygous Hypercholesterolemia on Lipoprotein Apheresis (CHAIN). An overall cohort included patients diagnosed with HoFH aged 0-18 years who were alive and in follow-up between Jan 1, 2010, and Nov 8, 2021, and whose high plasma LDL cholesterol concentrations made them eligible for lipoprotein apheresis. To compare cardiovascular outcomes, patients who initiated lipoprotein apheresis in childhood (lipoprotein apheresis group) and patients who only received lipid-lowering drugs (pharmacotherapy-only group) were matched by sex and untreated plasma LDL cholesterol concentrations. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischaemic stroke, percutaneous coronary intervention, coronary artery bypass grafting, aortic valve replacement, peripheral artery disease, carotid endarterectomy, angina pectoris, and supra-aortic or aortic stenosis (collectively referred to as atherosclerotic cardiovascular disease), for which survival analyses were performed in the matched cohort. Cox regression analyses were used to compare disease-free survival between cohorts and to calculate hazard ratio (HR) and 95% CI adjusted for sex, age at diagnosis, untreated plasma LDL cholesterol concentration, and number of lipid-lowering therapies other than lipoprotein apheresis. The overall cohort included 404 patients with a median age at diagnosis of 6·0 years (IQR 3·0-9·5) and median untreated plasma LDL cholesterol of 17·8 mmol/L (14·7-20·8). The matched cohorts included 250 patients (125 patients per group), with a median untreated LDL cholesterol of 17·2 mmol/L (14·8-19·7). Mean reduction in plasma LDL cholesterol concentrations between baseline and final follow-up was greater in the lipoprotein apheresis group (-55% [95% CI -60 to -51] vs -31% [-36 to -25]; p<0·0001). Patients in the lipoprotein apheresis group had longer atherosclerotic cardiovascular disease-free survival (adjusted HR 0·52 [95% CI 0·32-0·85]) and longer cardiovascular death-free survival (0·0301 [0·0021-0·4295]). Cardiovascular death was more common in the pharmacotherapy-only group than in the lipoprotein apheresis group (ten [8%] vs one [1%]; p=0·010), whereas median age at coronary artery bypass grafting was lower in the lipoprotein apheresis group than in the pharmacotherapy-only group (15·0 years [IQR 12·0-24·0] vs 30·5 years [19·0-33·8]; p=0·037). Among patients with HoFH, lipoprotein apheresis initiated during childhood and adolescence is associated with reduced long-term risk of atherosclerotic cardiovascular disease and death, and clear benefits of early initiation of high-frequency treatment on reducing plasma cholesterol were found. Consensus recommendations are now needed to guide more widespread and timely use of lipoprotein apheresis for children with HoFH, and research is required to further optimise treatment and ensure benefits of early and aggressive treatment delivery are balanced against effects on quality of life. Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; European Atherosclerosis Society; and the US National Heart, Lung, and Blood Institute, National Institutes of Health.

Long-term cardiovascular disease risk after anthracycline and trastuzumab treatments in US breast cancer survivors.

Although breast cancer survivors are at risk for cardiovascular disease (CVD) from treatment late effects, evidence to inform long-term and age-specific cardiovascular surveillance recommendations is lacking. We conducted a retrospective cohort study of 10 211 women diagnosed with first primary unilateral breast cancer in Kaiser Permanente Washington or Colorado (aged 20 years and older, survived ≥1 year). We estimated multivariable adjusted hazard ratios (HRs) for associations between initial chemotherapy regimen type (anthracycline and/or trastuzumab, other chemotherapies, no chemotherapy [referent]) and CVD risk, adjusted for patient characteristics, other treatments, and CVD risk factors. Cumulative incidence was calculated considering competing events. After 5.79 median years, 14.67% of women developed CVD (cardiomyopathy and/or heart failure [HF], ischemic heart disease, stroke). Women treated with anthracyclines and/or trastuzumab had a higher risk of CVD compared with no chemotherapy (adjusted HR = 1.53, 95% confidence interval [CI] = 1.31 to 1.79), persisting at least 5 years postdiagnosis (adjusted HR5-<10 years = 1.85, 95% CI = 1.44 to 2.39; adjusted HR≥10 years = 1.83, 95% CI = 1.34 to 2.49). Cardiomyopathy and/or HF risks were elevated among women treated with anthracyclines and/or trastuzumab compared with no chemotherapy, especially for those aged younger than 65 years (adjusted HR20-54years = 2.97, 95% CI = 1.72 to 5.12; adjusted HR55-64years = 2.21, 95% CI = 1.52 to 3.21), differing for older women (adjusted HR≥65 years = 1.32, 95% CI = 0.97 to 1.78), and at least 5 years postdiagnosis (adjusted HR5-<10years = 1.89, 95% CI = 1.35 to 2.64; adjusted HR≥10 years = 2.21, 95% CI = 1.52 to 3.20). Anthracyclines and/or trastuzumab receipt was associated with increased ischemic heart disease risks after 5 or more years (adjusted HR5-<10years = 1.51, 95% CI = 1.06 to 2.14; adjusted HR≥10 years = 1.86, 95% CI = 1.18 to 2.93) with no clear age effects, and stroke risk (adjusted HR = 1.33, 95% CI = 1.05 to 1.69), which did not vary by time or age. There was some evidence of long-term cardiomyopathy and/or HF and ischemic heart disease risks with other chemotherapies. Among women aged younger than 65 treated with anthracyclines and/or trastuzumab, up to 16% developed CVD by 10 years (20-54 years = 6.91%; 55-64 years = 16.00%), driven by cardiomyopathy and/or HF (20-54 years = 3.90%; 55-64 years = 9.78%). We found increased long-term risks of cardiomyopathy and/or HF and ischemic heart disease among breast cancer survivors treated with anthracyclines and/or trastuzumab and increased cardiomyopathy and/or HF risk among women aged younger than 65 years.

Independent Relationship of Lipoprotein(a) and Carotid Atherosclerosis With Long-Term Risk of Cardiovascular Disease.

Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.

Blood pressure responses to handgrip exercise but not apnea or mental stress are enhanced in women with a recent history of preeclampsia.

Preeclampsia is a risk factor for future cardiovascular diseases. However, the mechanisms underlying this association remain unclear, limiting effective prevention strategies. Blood pressure responses to acute stimuli may reveal cardiovascular dysfunction not apparent at rest, identifying individuals at elevated cardiovascular risk. Therefore, we compared blood pressure responsiveness with acute stimuli between previously preeclamptic (PPE) women (34 ± 5 yr old, 13 ± 6 mo postpartum) and women following healthy pregnancies (Ctrl; 29 ± 3 yr old, 15 ± 4 mo postpartum). Blood pressure (finger photoplethysmography calibrated to manual sphygmomanometry-derived values; PPE: n = 12, Ctrl: n = 12) was assessed during end-expiratory apnea, mental stress, and isometric handgrip exercise protocols. Integrated muscle sympathetic nerve activity (MSNA) was assessed in a subset of participants (peroneal nerve microneurography; PPE: n = 6, Ctrl: n = 8). Across all protocols, systolic blood pressure (SBP) was higher in PPE than Ctrl (main effects of group all P < 0.05). Peak changes in SBP were stressor specific: peak increases in SBP were not different between PPE and Ctrl during apnea (8 ± 6 vs. 6 ± 5 mmHg, P = 0.32) or mental stress (9 ± 5 vs. 4 ± 7 mmHg, P = 0.06). However, peak exercise-induced increases in SBP were greater in PPE than Ctrl (11 ± 5 vs. 7 ± 7 mmHg, P = 0.04). MSNA was higher in PPE than Ctrl across all protocols (main effects of group all P < 0.05), and increases in peak MSNA were greater in PPE than Ctrl during apnea (44 ± 6 vs. 27 ± 14 burst/100 hb, P = 0.04) and exercise (25 ± 8 vs. 13 ± 11 burst/100 hb, P = 0.01) but not different between groups during mental stress (2 ± 3 vs. 0 ± 5 burst/100 hb, P = 0.41). Exaggerated pressor and sympathetic responses to certain stimuli may contribute to the elevated long-term risk for cardiovascular disease in PPE.NEW & NOTEWORTHY Women with recent histories of preeclampsia demonstrated higher systolic blood pressures across sympathoexcitatory stressors relative to controls. Peak systolic blood pressure reactivity was exacerbated in previously preeclamptic women during small muscle-mass exercises, although not during apneic or mental stress stimuli. These findings underscore the importance of assessing blood pressure control during a variety of experimental conditions in previously preeclamptic women to elucidate mechanisms that may contribute to their elevated cardiovascular disease risk.

Associations between hysterectomy and metabolic syndrome: the Multi-Ethnic Study of Atherosclerosis

Metabolic syndrome is linked to an increased risk of incident cardiovascular disease and all-cause mortality. Notable associations exist between hysterectomy with bilateral salpingo-oophorectomy and metabolic syndrome. However, there is emerging evidence that even with ovarian conservation, hysterectomy may be independently associated with long-term cardiovascular disease risk. To examine the associations between hysterectomy with ovarian preservation and metabolic syndrome risk in a multiethnic cohort. We studied 3367 female participants in the Multi-Ethnic Study of Atherosclerosis who had data on self-reported history of hysterectomy, oophorectomy, hystero-oophorectomy, and metabolic syndrome at baseline (2000-2002). We used adjusted logistic regression to assess the cross-sectional associations between hysterectomy and or oophorectomy subgroups and prevalent metabolic syndrome at baseline. Furthermore, we investigated 1355 participants free of baseline metabolic syndrome and used adjusted Cox regression models to evaluate incident metabolic syndrome from examinations 2 (2002-2004) to 6 (2016-2018). The mean age was 59.0±9.5 years, with 42% White, 27% Black, 19% Hispanic, and 13% Chinese American participants. 29% and 22% had a history of hysterectomy and oophorectomy, respectively. Over a median follow-up of 10.5 (3.01-17.62) years, there were 750 metabolic syndrome events. Hysterectomy (hazard ratio, 1.32 [95% confidence interval, 1.01-1.73]) and hystero-oophorectomy (hazard ratio, 1.40 [95% confidence interval, 1.13-1.74]) were both associated with incident metabolic syndrome compared with having neither hysterectomy nor oophorectomy. Hysterectomy, even with ovarian preservation, may be independently associated with a higher risk of metabolic syndrome. If other studies confirm these findings, screening and preventive strategies focused on females with ovary-sparing hysterectomies and the mechanisms underpinning these associations may be explored.

Use of melatonin supplements and risk of type 2 diabetes and cardiovascular diseases in the USA: insights from three prospective cohort studies

Use of melatonin supplements has been increasing substantially in both children and adults in the USA; however, their long-term cardiometabolic effects remain unclear. We aimed to assess the associations between regular use of melatonin supplements and the risk of developing type 2 diabetes or cardiovascular disease in adults. In this study, we included individuals from three US cohorts: the Nurses' Health Study (women only), the Health Professionals Follow-up Study (men only), and the Nurses' Health Study II (women only). Women aged 25-55 years and men aged 45-75 years at baseline, who had no diagnosis of cancer at baseline, and who responded to the question about melatonin supplement use (yes or no) were included. We excluded baseline prevalent cardiovascular disease and baseline prevalent type 2 diabetes for the main analyses. The main outcomes were cardiovascular disease and type 2 diabetes incidence. In secondary analyses, we stratified by duration of rotating night shift work in the Nurses' Health Study and Nurses' Health Study II to examine whether the associations with melatonin supplement use differed by rotating night shift work. For the cardiovascular disease analysis, we included 67 202 women from the Nurses' Health Study (follow-up 1998-2019, mean age at baseline: 63·6 years [SD 7·1]), 26 629 men from the Health Professionals Follow-up Study (1998-2020, 62·9 years [8·8], and 65 241 women from the Nurses' Health Study II (2003-19, 48·2 years [4·7]). Follow-up for incident type 2 diabetes was from 1998 to June 30, 2021, for the Nurses' Health Study; 2003 to Jan 31, 2023, for the Nurses' Health Study II; and from 1998 to Jan 31, 2020, for the Health Professionals' Follow-up Study. Melatonin supplement use in the study cohorts doubled over recent decades from less than 2% in 1998-2007 to 4% or higher in 2014-15 (4·0% in men and 5·3% in women). We documented 16 917 incident cardiovascular disease events during 2 609 068 person-years of follow-up and 12 730 incident cases of type 2 diabetes during 2 701 830 person-years of follow-up. In a pooled analysis of the three cohorts, comparing users with non-users of melatonin supplements, the pooled multivariable-adjusted hazard ratios were 0·94 (95% CI 0·83-1·06, p=0·32) for cardiovascular disease and 0·98 (0·86-1·12, p=0·80) for type 2 diabetes. In secondary analyses, melatonin supplement use appeared to attenuate the positive association between long-term shift work (>5 years) and risk of cardiovascular disease (pinteraction=0·013) among the female nurses. With up to 23 years of follow-up of three large prospective cohorts of middle-aged and older men and women, self-reported melatonin supplement use was not associated with risk of type 2 diabetes or cardiovascular disease. Further research is warranted to assess if melatonin supplement use could mitigate the potential risks of type 2 diabetes and cardiovascular disease associated with rotating night shift work. US National Institutes of Health.

OBSTRUCTIVE SLEEP APNEA REMAINS A RISK FACTOR FOR MAJOR ADVERSE CARDIOVASCULAR AND CEREBROVASCULAR EVENTS IN HYPERTENSVIE PATIENTS UNDER TREATMENT: THE UROSAH DATA

Objective: The impact of the co-occurrence of hypertension and obstructive sleep apnea (OSA) on the risk of long-term cardiovascular disease (CVD) outcomes has not been extensively studied in the Asian population, and the residual effect of OSA on CVD in patients under antihypertensive treatment is not clear. The study aimed to explore the impact of OSA on the risk of CVD outcomes in a large-scale Asian cohort under antihypertensive treatment using retrospective design. Design and method: Hypertensive patients who underwent polysomnography (PSG) test in January 2011 to December 2013 were recruited from the UROSAH cohort, which was conducted in Hypertension Center of People's Hospital. OSA was defined as apnea hypopnea index over 5. Outcomes were extended major adverse cardiovascular and cerebrovascular events (MACCE), including the first occurrence of nonfatal myocardial infarction, nonfatal stroke, revascularization, rehospitalization due to unstable angina or heart failure and all-cause death. Cox regression analysis was performed to explore the effect of OSA and hypertension coexistence on MACCE. Results: A total of 3329 hypertension patients were enrolled, of whom 2585 patients (about 77.7%) suffered from OSA. During a median follow-up period of 7.0 years, 415 patients developed extended MACCE. The incidence of extended MACCE was significantly greater in patients with OSA than those without OSA (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.27-1.99; P&lt;0.001). Overall, patients with OSA had an increased risk of cardiac events of 57% compared to those without OSA [HR (95%CI): 1.57 (1.04-2.39), P=0.034] and the association did not change in further sensitivity analysis. Particularly in uncontrolled hypertension, OSA was found to have a 93% increased risk of cardiac events, compared with patients without OSA (P=0.036). Conclusions: Untreated OSA seemed to be a factor affecting the prognosis of cardiac events in hypertensive patients, although the association between OSA and cardiac events would be attenuated by the pharmacological-induced blood pressure control, which highlights the need to treat OSA.

Socioeconomic disadvantage in pregnancy and postpartum risk of cardiovascular disease

Pregnancy is an educable and actionable life stage to address social determinants of health (SDOH) and lifelong cardiovascular disease (CVD) prevention. However, the link between a risk score that combines multiple neighborhood-level social determinants in pregnancy and the risk of long-term CVD remains to be evaluated. To examine whether neighborhood-level socioeconomic disadvantage measured by the Area Deprivation Index (ADI) in early pregnancy is associated with a higher 30-year predicted risk of CVD postpartum, as measured by the Framingham Risk Score. An analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study longitudinal cohort. Participant home addresses during early pregnancy were geocoded at the Census-block level. The exposure was neighborhood-level socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]) measured in the first trimester. Outcomes were the predicted 30-year risks of atherosclerotic cardiovascular disease (ASCVD, composite of fatal and nonfatal coronary heart disease and stroke) and total CVD (composite of ASCVD plus coronary insufficiency, angina pectoris, transient ischemic attack, intermittent claudication, and heart failure) using the Framingham Risk Score measured 2 to 7years after delivery. These outcomes were assessed as continuous measures of absolute estimated risk in increments of 1%, and, secondarily, as categorical measures with high-risk defined as an estimated probability of CVD ≥10%. Multivariable linear regression and modified Poisson regression models adjusted for baseline age and individual-level social determinants, including health insurance, educational attainment, and household poverty. Among 4309 nulliparous individuals at baseline, the median age was 27years (interquartile range [IQR]: 23-31) and the median ADI was 43 (IQR: 22-74). At 2 to 7years postpartum (median: 3.1years, IQR: 2.5, 3.7), the median 30-year risk of ASCVD was 2.3% (IQR: 1.5, 3.5) and of total CVD was 5.5% (IQR: 3.7, 7.9); 2.2% and 14.3% of individuals had predicted 30-year risk ≥10%, respectively. Individuals living in the highest ADI tertile had a higher predicted risk of 30-year ASCVD % (adjusted ß: 0.41; 95% confidence interval [CI]: 0.19, 0.63) compared with those in the lowest tertile; and those living in the top 2 ADI tertiles had higher absolute risks of 30-year total CVD % (T2: adj. ß: 0.37; 95% CI: 0.03, 0.72; T3: adj. ß: 0.74; 95% CI: 0.36, 1.13). Similarly, individuals living in neighborhoods in the highest ADI tertile were more likely to have a high 30-year predicted risk of ASCVD (adjusted risk ratio [aRR]: 2.21; 95% CI: 1.21, 4.02) and total CVD ≥10% (aRR: 1.35; 95% CI: 1.08, 1.69). Neighborhood-level socioeconomic disadvantage in early pregnancy was associated with a higher estimated long-term risk of CVD postpartum. Incorporating aggregated SDOH into existing clinical workflows and future research in pregnancy could reduce disparities in maternal cardiovascular health across the lifespan, and requires further study.

Sex Differences in Hemodynamic and Autonomic Reactivity during Cold Pressor Test in Chronic Kidney Disease

Introduction: Chronic kidney disease (CKD) is characterized by sympathetic nervous system (SNS) overactivity that contributes to increased cardiovascular risk. Hemodynamic reactivity during the cold pressor test (CPT) has been widely used to evaluate sympathetic neural control in patient populations, and increased neurocardiovascular reactivity to CPT has been shown to predict greater risk of future cardiovascular events. Prior studies have suggested that males with CKD have higher long-term cardiovascular disease risk compared to females with CKD; however, whether sex differences in neurocardiovascular responsivity during CPT exists within CKD remains unknown. Objectives: Our primary objective was to evaluate potential sex differences in hemodynamic and autonomic reactivity during CPT in patients with CKD. Hypothesis: Males with CKD have an augmented pressor and sympathetic response to sympathoexcitation induced by CPT compared with females with CKD. Methods: Patients with CKD (Stage III and IV) with stable renal function were included. Continuous beat to beat blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) by microneurography were measured at rest for 10 minutes and during CPT that consisted of immersion of the hand to the wrist in ice water (4–5 °C) for one minute, followed by a 5-min recovery period. Results: 25 participants with CKD were included (N= 14 male, N=11 female). There were no differences in baseline characteristics, resting hemodynamics or MSNA between male and female groups. Males with CKD had a steeper rate of increase and higher peak levels of diastolic BP (DBP, 101±3 vs 87±3; p=0.008) and mean arterial BP (MAP, 130±4 vs 112±5 mm Hg, p=0.023) during CPT compared to females with CKD, respectively. Conversely, females with CKD had a steeper rate of increase in HR during CPT compared to males. MSNA increased in both males and females during CPT; however, there was no difference in MSNA reactivity during CPT between groups. Conclusions: Males with CKD had greater BP reactivity during CPT compared to females with CKD, while females with CKD had greater HR reactivity during CPT compared to males. There was no difference in sympathetic reactivity between groups. Augmented BP reactivity during CPT in males with CKD may contribute to sex differences in cardiovascular disease risk in patients with CKD. Supported by NIH Grants R33AT010457 and R01HL135183. 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.

Association of Disrupted Delta Wave Activity During Sleep With Long-Term Cardiovascular Disease and Mortality

BackgroundDelta wave activity is a prominent feature of deep sleep, which is significantly associated with sleep quality. ObjectivesThe authors hypothesized that delta wave activity disruption during sleep could predict long-term cardiovascular disease (CVD) and CVD mortality risk. MethodsThe authors used a comprehensive power spectral entropy-based method to assess delta wave activity during sleep based on overnight polysomnograms in 4,058 participants in the SHHS (Sleep Heart Health Study) and 2,193 participants in the MrOS (Osteoporotic Fractures in Men Study) Sleep study. ResultsDuring 11.0 ± 2.8 years of follow-up in SHHS, 729 participants had incident CVD and 192 participants died due to CVD. During 15.5 ± 4.4 years of follow-up in MrOS, 547 participants had incident CVD, and 391 died due to CVD. In multivariable Cox regression models, lower delta wave entropy during sleep was associated with higher risk of coronary heart disease (SHHS: HR: 1.46; 95% CI: 1.02-2.06; P = 0.03; MrOS: HR: 1.79; 95% CI: 1.17-2.73; P < 0.01), CVD (SHHS: HR: 1.60; 95% CI: 1.21-2.11; P < 0.01; MrOS: HR: 1.43; 95% CI: 1.00-2.05; P = 0.05), and CVD mortality (SHHS: HR: 1.94; 95% CI: 1.18-3.18; P < 0.01; MrOS: HR: 1.66; 95% CI: 1.12-2.47; P = 0.01) after adjusting for covariates. The Shapley Additive Explanations method indicates that low delta wave entropy was more predictive of coronary heart disease, CVD, and CVD mortality risks than conventional sleep parameters. ConclusionsThe results suggest that delta wave activity disruption during sleep may be a useful metric to identify those at increased risk for CVD and CVD mortality.