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Background Younger age at final menstrual period (FMP) is associated with increased risk for cardiovascular disease events. This paper evaluated whether older age at FMP is associated with more favorable patterns of lipid changes during the menopause transition and whether these changes are associated with less subclinical carotid disease in the postmenopausal years. Methods and Results Lipids and lipoproteins were measured repeatedly among 1554 premenopausal women who had a natural menopause during follow‐up years (median=18.8 years); a subset of 890 women also had measures of carotid intima media thickness, adventitial diameter, and plaque. Women who had an older FMP age had less adverse changes in cholesterol from 1 to 3 years after FMP, and in triglycerides from FMP to 3 years after FMP, but they had more adverse changes in ApoB and Apo A1 from 3 years before to 1 year after the FMP. Increasing cholesterol and ApoB from 1 to 3 years after FMP were associated with greater intima media thickness and adventitial diameter, and the greater likelihood of a plaque score >2 the older the age at FMP. Conclusions Despite the epidemiological literature showing early age at FMP is associated with elevated risk for cardiovascular disease events, older age at FMP had inconsistent associations with less adverse lipid changes in midlife, which did not translate into less risk for subclinical carotid disease and in some cases more risk. These findings are restricted to women who experience FMP in the normative age range for the menopausal transition.

Background Arterial stiffness predicts the risk of cardiovascular events and all‐cause mortality and is associated with age and hypertension. However, the magnitude of the relationship between blood pressure (BP) and progression of arterial stiffness is unclear, limiting our understanding of how arterial stiffness mediates clinical effects of hypertension and planning of clinical trials. Methods and Results Medline and EMBASE were searched for prospective studies reporting linear models between baseline BP and progression of arterial stiffness, with and without adjustment for demographic characteristics and baseline stiffness. Standardized and unstandardized β coefficients for pulse wave velocity were combined by fixed and random effects meta‐analysis, weighted by the inverse variance. Of 566 fully reviewed articles from 30, 524 titles, 22 populations from 21 reports were included. In 9 cohorts, there were consistent, adjusted associations between baseline systolic BP and progression of arterial stiffness (11 781 patients; standardized β=0.041; 95% CI, 0.026–0.055; P P value for heterogeneity=0.70), equivalent to a 1.14‐m/s increase in standard carotid‐femoral pulse wave velocity per decade per 20–mm Hg systolic BP, independent of age. Unstandardized, adjusted associations were similar (1762 patients; β=0.0047; 95% CI, 0.004–0.006; P P value for heterogeneity=0.64), equivalent to a 0.94‐m/s increase per decade per 20–mm Hg systolic BP. In limited studies, standardized associations between mean BP and arterial stiffness progression were not significant and heterogeneous (913 patients; β=0.039; 95% CI, −0.008 to 0.086; P =0.11; P value for heterogeneity=0.03). Conclusions Baseline systolic BP was associated with a clinically important progression of arterial stiffness, independent of age, providing a reference for the potential effect of arterial stiffness in mediating changes in clinical outcomes associated with hypertension and providing a reference value to aid clinical trial design.

Background Women who deliver preterm infants ( Methods and Results We identified 1306 women (51% Black) with births between baseline (1985–1986) and year 30 in the CARDIA (Coronary Artery Risk Development in Young Adults) study. We compared life course changes in blood pressure, body mass index, waist circumference, and lipids in women with preterm deliveries (n=318) with those with all term deliveries (n=988), using piecewise linear mixed‐effects models. Specifically, we evaluated group differences in rates of change before and after the childbearing period and change in level across the childbearing period. After adjusting for the covariates, women with preterm deliveries had a higher change in diastolic blood pressure across the childbearing period than those with all term deliveries (1.59 versus −0.73 mm Hg, P 2 , P =0.03) compared with those with all term deliveries, followed by a steeper increase after the childbearing period (0.22 versus 0.17 kg/m 2 per year, P =0.02). Conclusions Preterm delivery was associated with unfavorable patterns of change in diastolic blood pressure and adiposity that originate during the childbearing years and persist or exacerbate later in life. These adverse changes may contribute to the elevated cardiovascular risk among women with preterm delivery.

Background Childhood adversity and trauma have been shown to be associated with poorer cardiovascular disease (CVD) outcomes in adulthood. However, longitudinal studies of this association are rare. Methods and Results Our study used the CARDIA (Coronary Artery Risk Development in Young Adults) Study, a longitudinal cohort that has followed participants from recruitment in 1985–1986 through 2018, to determine how childhood psychosocial environment relates to CVD incidence and all‐cause mortality in middle age. Participants (n=3646) completed the Childhood Family Environment (CFE) questionnaire at the year 15 (2000–2001) CARDIA examination and were grouped by high, moderate, or low relative CFE adversity scores. We used sequential multivariable regression models to estimate hazard ratios of incident (CVD) and all‐cause mortality. Participants were 25.1±3.6 years old, 47% black, and 56% female at baseline and 198 participants developed CVD (17.9 per 10 000 person‐years) during follow‐up. CVD incidence was >50% higher for those in the high CFE adversity group compared with those in the low CFE adversity group. In fully adjusted models, CVD hazard ratios (95% CI) for participants who reported high and moderate CFE adversity versus those reporting low CFE adversity were 1.40 (0.98–2.11) and 1.25 (0.89–1.75), respectively. The adjusted hazard ratios for all‐cause mortality was 1.68 (1.17–2.41) for those with high CFE adversity scores and 1.55 (1.11–2.17) for those with moderate CFE adversity scores. Conclusions Adverse CFE was associated with CVD incidence and all‐cause mortality later in life, even after controlling for CVD risk factors in young adulthood.

Background Atrial fibrillation ( AF ) is associated with cognitive decline. Whether left atrial enlargement ( LAE ), a critical substrate for AF, is also associated is less well established. Therefore, we assessed the association of LAE and AF with cognitive decline in the ARIC‐NCS (Atherosclerosis Risk in Communities Neurocognitive Study). Methods and Results Participants (n=3391; mean age, 75±5 years; 59% women) underwent cognitive tests and 2‐dimensional echocardiograms at visit 5 (2011–2013) and follow‐up cognitive tests at visit 6 (2016–2017). LAE was defined as left atrium volume index ≥34 mL/m 2 . AF was ascertained using study ECG s and hospitalization discharge codes. We assessed the association of AF and LAE with (a) cognitive domain scores at visit 5 and (b) cognitive domain score changes between visit 5 and visit 6. At visit 5, compared with the reference group (without AF , normal left atrium), participants with LAE and AF had significantly lower global cognition ( Z score, −0.24; 95% CI, −0.38 to −0.10), whereas participants with AF and without LAE and participants with LAE and without AF did not have lower global cognition. In longitudinal analysis, compared with the reference group, participants with AF but without LAE had significantly greater decline in global cognition ( Z score, −0.13; 95% CI, −0.21 to −0.06). However, LAE, with or without AF, was not associated with greater cognitive decline. Conclusion Although LAE with AF was significantly associated with lower cognitive function in cross‐sectional analysis, LAE, with or without AF, was not associated with greater cognitive decline over 5 years, highlighting the importance of evaluating longitudinal cognitive function. Future studies should have longer follow‐up and evaluate left atrium function.

Background The association between low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and triglycerides with cardiovascular disease ( CVD ) has been well studied. No previous studies considered trajectory of these lipids jointly. This study aims to characterize longitudinal trajectories of lipid profile jointly and examine its impact on incident CVD . Methods and Results A total of 9726 participants (6102 men), aged from 20 to 58 years who had lipids repeatedly measured 3 to 9 times, were included in the study. Three distinct trajectories were identified using the multivariate latent class growth mixture model: inverse U‐shape (18.72%; n=1821), progressing (66.03%; n=6422), and U‐shape (15.25%; n=1483). Compared with the U‐shape class, the adjusted hazard ratio and 95% CI were 1.33 (1.05–1.68) and 1.49 (1.14–1.95) for the progressing and inverse U‐shape class, respectively. The area under the curve was calculated using the integral of the model parameters. In the adjusted model, total and incremental area under the curve of lipid profile were significantly associated with CVD risk. Furthermore, the model‐estimated levels and linear slopes of lipids were calculated at each age point according to the latent class growth mixture model model parameters and their first derivatives, respectively. After adjusting for covariates, standardized odds ratio of slope increases gradually from 1.11 (1.02, 1.21) to 1.21 (1.12, 1.31) at 20 to 40 years and then decreased to 1.02 (0.94, 1.11) until 60 years. Conclusions These results indicate that the lipids profile trajectory has a significant impact on CVD risk. Age between 20 and 42 years is a crucial period for incident CVD , which has implications for early lipids intervention.

Background Although hypertension and microalbuminuria are closely interrelated, the magnitude and temporal sequence of the bidirectional association between hypertension and microalbuminuria are largely unknown. We aimed to delineate the bidirectional and temporal relationship between hypertension and microalbuminuria. Methods and Results Leveraging a longitudinal cohort of Chinese adults who had blood pressure and urinary albumin measured twice 4 years apart, we examined the temporal association between hypertension and microalbuminuria by bidirectional and cross‐lagged panel analysis. All participants were free of cardiovascular disease and chronic kidney disease at baseline. Bidirectional association analysis found that baseline microalbuminuria predicted the risk of incident hypertension (odds ratio=1.75, P =0.028), and baseline blood pressure also significantly predicted the risk of microalbuminuria (odds ratios=1.27 and 1.21 for a per‐SD increase in systolic and diastolic blood pressure, respectively; all P P =0.079), which is significantly weaker than the other direction of the relationship of baseline urinary albumin to follow‐up blood pressures (all P Conclusions These findings indicate a significant bidirectional association between microalbuminuria and hypertension in Chinese adults. Elevated urinary albumin excretion is more likely to precede hypertension. The causality between microalbuminuria and hypertension needs further investigation.

Elevated blood pressure is a leading cause of cardiovascular disease and related disability worldwide.1 It is a largely preventable condition influenced by a range of lifestyle behaviors, including but not limited to level of physical activity, poor diet, and alcohol consumption. In this issue of the Journal of the American Heart Association (JAHA), 2 articles make important incremental contributions in extending the evidence base of the latter. Roerecke and colleagues2 carried out a systematic review and dose–response meta‐analysis of the association between alcohol consumption, defined using average number of drinks consumed per day, and incident hypertension separately in men and women. They found that no level of alcohol intake was associated with a lower risk of developing hypertension in either sex, which is in contrast to previous systematic reviews of this topic as well as observational studies of alcohol consumption and some cardiovascular outcomes.3, 4 Piano and co‐workers5 provide complementary findings, focusing on the cross‐sectional association of episodic heavy drinking (often referred to as “binge drinking” as the authors chose to, defined as men or women consuming 5 or 4 or more drinks in a single day, respectively) and indicators of cardiometabolic health, including blood pressure, in younger people. They found that frequency of binge drinking was associated with elevated levels of systolic blood pressure in men but not women. This result is in some ways supported by the work of Roerecke et al,2 who similarly found a less pronounced effect of average alcohol intake on risk of developing hypertension in women. However, this study regrettably falls short of “completing the puzzle” of whether this difference in association with blood pressure by sex is driven by variation in drinking pattern (ie, episodes of heavy drinking being more common in men) through having not included either adjustment for, or the formal testing of an interaction with, overall volume of alcohol consumed. Notwithstanding this unfortunate missed opportunity, the results of the study by Piano et al5 are valuable in their own right through reminding us that the drinking habits we adopt in early adulthood and middle age (a time when we are typically free from disease) correlate with premorbid indicators of cardiovascular health. Considering their findings, both sets of authors rightly call for changes in clinical practice to reduce the burden of alcohol‐related hypertension. This viewpoint is by no means controversial, given the wealth of data now available suggesting that alcohol consumption, even at levels typically considered “moderate”, is causally associated with elevated blood pressure (and increased risk of developing certain types of cancer and other disorders).6 However, it could be argued that the suggestion from both teams that screening and counseling for alcohol consumption should be carried out when hypertension is present is not proactive enough if the goal of doing so is to minimize raised blood pressure (and through doing so lower the burden of cardiovascular disease) at a population level. It is vital that one considers cardiovascular health and its determinants from a life course perspective.1, 7, 8 Raised blood pressure with advancing age is not observed in all societies,9 suggesting that this is not an inevitable part of the aging process. It is for this reason that ensuring healthy lifestyle behaviors are adopted early and maintained across the life course has the potential to substantially reduce, and perhaps even eliminate, cardiovascular disease in the population. The benefits of intervening early in the health‐disease continuum have already been elegantly demonstrated for systolic blood pressure.10 Exposure to (“genetically determined”) higher levels of systolic blood pressure is associated with more rapid increases in blood pressure with age, even before the development of hypertension. This indicates that lowering systolic blood pressure before it becomes elevated may slow or attenuate age‐related changes in blood pressure. While this finding should be enough to convince most that adopting a life course perspective is crucial to the prevention of cardiovascular disease, the same study also revealed that systolic blood pressure appears to have a cumulative effect on risk of developing coronary heart disease, such that the reduction in risk is proportional to the average time exposed to lower blood pressure. The public health mantra that an ounce of prevention is worth a pound of cure certainly applies in this scenario. Waiting until the problem is overt is suboptimal for at least 2 reasons: first, we are not reducing the collective time an individual is subjected to a state of elevated systolic blood pressure, and second, it may be too late if hypertension (which is usually asymptomatic in the initial stages) has already led to accelerated atherosclerosis or irreversible damage to major organs. However, as Roerecke et al2 note, the association of alcohol consumption with cardiovascular end points is not always linear, or necessarily negative (this is echoed in the work of Piano et al5 also).3 This leaves public health officials and clinicians in some ways stuck between a rock and a hard place when it comes to providing advice on alcohol consumption. While it might appear a simple task on paper, the reality of what counsel to provide a patient seeking advice on alcohol consumption and health is not necessarily straightforward.11 This is perhaps one of the reasons why clinicians may be reluctant to inquire about, or provide advice on, alcohol consumption in primary care, even in situations where it might be beneficial to do so.12 For example, barely a of quarter of individuals in the United States presenting to their general practitioner with hypertension are recommended to reduce their alcohol intake as a nonpharmacological means of controlling their blood pressure.13 On the other hand, there are clinicians who have gone as far as recommending that nondrinkers over 40 years of age consider taking up drinking as a means of extending their life and lowering their risk of developing cardiovascular disease.14 However, this has mostly been met with cynicism,15 even among proponents of the hypothesis that moderate drinking confers cardiovascular benefits11, 16 and certainly no major public health body endorses such advice. The largest study to date of the dose–response association between alcohol consumption and selected cardiovascular outcomes and all‐cause mortality, among those who choose to drink, calculated that the excess risk associated with each additional standard alcoholic drink within the confines of most international drinking guidelines is at a level most would consider acceptable for practically all outcomes investigated.4 It is important to remember that people consume alcohol for pleasure and most do so responsibly. The majority of researchers do not actively advocate that people stop drinking but merely seek to emphasize that reductions in consumption can reduce one's overall risk of prematurely developing disease and/or dying. However, this subtle point can occasionally be lost in translation when findings from studies are communicated to the public via the media (sometimes without the involvement of the researchers themselves in this process). As such, public health professionals can quickly be branded as enemies of the people17 for being perceived as trying to push a temperance agenda upon people who are perfectly content with their current level of consumption. Nevertheless, it is clear that a substantial proportion of the population are not fully aware of the risks associated with (even minimal) alcohol consumption,18 and there is evidence that those who believe alcohol confers cardioprotective effects tend to drink more on average than those who do not.19 As such, it is important that the evidence base for alcohol consumption and health continues to be debated in public (including the strengths, limitations, sources of bias, and degree of uncertainty of the collective pool of knowledge). But perhaps rather than messages simply re‐stating that drinking alcohol (or not drinking as it may be) is associated with an increased risk of disorder X, that can sometimes be perceived as condescending (and may lead to people disengaging),20 they might instead be packaged in a way that is easily interpretable and/or tailored to an individual, such as absolute differences in risk for someone of their age with otherwise similar characteristics. It is also important to remember that health is dynamic and there is no such thing as a one‐size‐fits‐all approach to managing risk. An individual's decision to drink, and at what level, should be motivated by their own personal circumstances.3 Population‐level initiatives, such as recommended drinking limits, can only go so far, after which individual‐level approaches are needed. Therefore, it is vital that an open and honest dialogue about alcohol consumption be initiated and maintained.18 What level of alcohol consumption might be considered acceptable for 1 individual may not be for another; equally, an individual might wish to consider changing their drinking habits if their situation changes. Ultimately, our job boils down to empowering an individual to make an informed decision about their level of alcohol intake and how this may influence their long‐ and short‐term health through transparent communication.

Background Few data exist on the association between strength training and mortality rates. We sought to examine the association between strength training and all‐cause, cardiovascular disease, and cancer mortality. Methods and Results Beginning in 2001 to 2005, 28 879 women throughout the United States (average baseline age, 62.2 years) from the Women's Health Study who were free of cardiovascular disease, diabetes mellitus, and cancer reported their physical activities, including strength training. During follow‐up (average, 12.0 years) through 2015, investigators documented 3055 deaths (411 from cardiovascular disease and 748 from cancer). After adjusting for covariables, including aerobic activity, time in strength training showed a quadratic association with all‐cause mortality (P=0.36 for linear trend; P1.00 for ≥146 min/wk of strength training. However, confidence intervals were wide at higher levels of strength training. Conclusions Time in strength training showed a J‐shaped association with all‐cause mortality in older women. A moderate amount of time in strength training seemed beneficial for longevity, independent of aerobic activity; however, any potential risk with more time (≈≥150 min/wk) should be further investigated.

Background In contrast to the effects of preterm birth, the extent to which shorter gestational age affects the cardiorespiratory fitness ( CRF ) levels of individuals who were born at term (ie, between 37 and 42 weeks) is largely unknown. The aim of this study was to examine whether life‐course CRF levels varied across different gestational ages within the at‐term range. Methods and Results The association between gestational age (in weeks) obtained from Child Health Services records and CRF , estimated from field and laboratory tests and expressed by maximal oxygen uptake level through adolescence to young adulthood, was examined in 791 participants in the Northern Ireland Young Hearts Study, all singletons born at term. Longitudinal data were analyzed with generalized estimating equations, accounting for important potential confounders. Mean levels of CRF were 45.6, 43.7, and 33.0 mL/kg per minute when participants were aged 12, 15, and 22 years, respectively. After adjustment for confounders, each week increase in gestational age was associated with 0.46 mL/kg per minute (95% confidence interval , 0.14–0.79) in CRF . Compared with individuals born full term (39–40 weeks, n=533) or late term (41–42 weeks, n=148), those who were born early term (37–38 weeks, n=110) had a higher incidence of poor CRF (risk ratio, 1.57; 95% confidence interval , 1.14–2.16). The changes in CRF through adolescence to young adulthood were similar across groups, with those born early term consistently displaying the lowest CRF. Conclusions These findings suggest that early‐term births within the at‐term range are linked to poorer CRF through adolescence to young adulthood, and may have important clinical and public health implications for policies about (avoidable) early‐term deliveries given their recent increasing trends.

Background Emerging evidence suggests that arterial stiffness, an important marker of cardiovascular health, is associated with alcohol consumption. However, the role of longer‐term consumption patterns in the progression of arterial stiffness over time remains unclear. A longitudinal cohort design was used to evaluate the association between alcohol consumption over 25 years and subsequent changes in arterial stiffness. Methods and Results Data (N=3869; 73% male) were drawn from the Whitehall II cohort study of British civil servants, in which participants completed repeat pulse wave velocity assessments of arterial stiffness across a 4‐ to 5‐year interval. Repeated alcohol intake measurements were used to categorize participants into alcohol consumer types, accounting for longitudinal variability in consumption. Sex‐stratified linear mixed‐effects modeling was used to investigate whether drinker types differed in their relationship to pulse wave velocity and its progression over time. Males with consistent long‐term heavy intake >112 g of ethanol/week had significantly higher baseline pulse wave velocity (b=0.26 m/s; P=0.045) than those who drank consistently moderately (1–112 g of ethanol/week). Male former drinkers showed significantly greater increases in arterial stiffness longitudinally compared to consistently moderate drinkers (b=0.11 m/s; P=0.009). All associations were nonsignificant for females after adjustment for body mass index, heart rate, mean arterial pressure, diabetes mellitus, high‐density lipoprotein, and triglycerides. Conclusions This work demonstrates that consistently heavy alcohol consumption is associated with higher cardiovascular risk, especially among males, and also provides new insights into the potential impact of changes in drinking levels over time. It discusses the additional insights possible when capturing longitudinal consumption patterns in lieu of reliance on recent intake alone. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02663791.

Background There are few longitudinal studies that have comprehensively examined the intima‐media thickness ( IMT ) growth pattern and its determinants among racial population groups. Methods and Results Mean and maximum IMT were measured by B‐mode ultrasonography up to 3 times in 253 white and 268 black participants, aged 13 to 36 years (mean age±standard deviation 24±3.2 years old). The development of IMT was assessed using individual growth curve modeling. A total of 521 participants with 1015 IMT measurements were eligible for this study. We found higher IMT in both left and right sides in blacks compared to whites ( P IMT with age. Body mass index and father's education level were associated with mean IMT , and only body mass index was associated with maximum IMT ( P IMT , suggesting that blacks and whites developed IMT in similar patterns. Interestingly, we found a faster increase in mean left‐side IMT than mean right‐side IMT (χ 2 =11.5, P Conclusions Our findings provide compelling prospective evidence that blacks may have thicker IMT compared to whites as young adults. These racial differences could not be explained by traditional risk factors. This implies that differences in this precursor of atherosclerosis may explain racial disparity in cerebrovascular disease.

Background Although research has demonstrated that depressive symptoms predict stroke incidence, depressive symptoms are dynamic. It is unclear whether stroke risk persists if depressive symptoms remit. Methods and Results Health and Retirement Study participants (n=16 178, stroke free and noninstitutionalized at baseline) were interviewed biennially from 1998 to 2010. Stroke and depressive symptoms were assessed through self-report of doctors’ diagnoses and a modified Center for Epidemiologic Studies - Depression scale (high was ≥3 symptoms), respectively. We examined whether depressive symptom patterns, characterized across 2 successive interviews (stable low/no, onset, remitted, or stable high depressive symptoms) predicted incident stroke (1192 events) during the subsequent 2 years. We used marginal structural Cox proportional hazards models adjusted for demographics, health behaviors, chronic conditions, and attrition. We also estimated effects stratified by age (≥65 years), race or ethnicity (non-Hispanic white, non-Hispanic black, Hispanic), and sex. Stroke hazard was elevated among participants with stable high (adjusted hazard ratio 2.14, 95% CI 1.69 to 2.71) or remitted (adjusted hazard ratio 1.66, 95% CI 1.22 to 2.26) depressive symptoms compared with participants with stable low/no depressive symptoms. Stable high depressive symptom predicted stroke among all subgroups. Remitted depressive symptoms predicted increased stroke hazard among women (adjusted hazard ratio 1.86, 95% CI 1.30 to 2.66) and non-Hispanic white participants (adjusted hazard ratio 1.66, 95% CI 1.18 to 2.33) and was marginally associated among Hispanics (adjusted hazard ratio 2.36, 95% CI 0.98 to 5.67). Conclusions In this cohort, persistently high depressive symptoms were associated with increased stroke risk. Risk remained elevated even if depressive symptoms remitted over a 2-year period, suggesting cumulative etiologic mechanisms linking depression and stroke.