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Hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, are associated with an increased risk of CVD.
Objectives
The purpose of this study was to evaluate associations between HDP and long-term CVD and identify the proportion of the association mediated by established CVD risk factors.
Methods
Parous participants without CVD in the Nurses’ Health Study II (n = 60,379) were followed for incident CVD from first birth through 2017. Cox proportional hazards models estimated HRs and 95% CIs for the relationship between HDP and CVD, adjusting for potential confounders, including prepregnancy body mass index, smoking, and parental history of CVD. To evaluate the proportion of the association jointly accounted for by chronic hypertension, hypercholesterolemia, type 2 diabetes, and changes in body mass index, we used the difference method.
Results
Women with HDP in first pregnancy had a 63% higher rate of CVD (95% CI: 1.37-1.94) compared with women with normotensive pregnancies. This association was mediated by established CVD risk factors (proportion mediated = 64%). The increased rate of CVD was higher for preeclampsia (HR: 1.72; 95% CI: 1.42-2.10) than gestational hypertension (HR: 1.41; 95% CI: 1.03-1.93). Established CVD risk factors accounted for 57% of the increased rate of CVD for preeclampsia but 84% for gestational hypertension (bothP <0.0001).
Conclusions
Established CVD risk factors arising after pregnancy explained most (84%) of the increased risk of CVD conferred by gestational hypertension and 57% of the risk among women with preeclampsia. Screening for chronic hypertension, hypercholesterolemia, type 2 diabetes, and overweight/obesity after pregnancy may be especially helpful in CVD prevention among women with a history of HDP.
Introduction
New-onset hypertensive disorders of pregnancy (HDP) (gestational hypertension and preeclampsia) occur in approximately 15% of parous women and are consistently associated with a 2-fold increased risk of cardiovascular disease (CVD) and premature CVD-related mortality, compared with women with a history of normotensive pregnancy.1,2However, few studies of incident CVD after hypertensive pregnancies have adjusted for shared prepregnancy risk factors, such as body mass index (BMI),3-5or had a mean/median follow-up of more than 30 years.4,6-9
Women with a history of HDP have elevated risks of chronic hypertension, hypercholesterolemia, and type 2 diabetes mellitus (T2DM), and the American Heart Association and American College of Cardiology endorse preeclampsia as a risk-enhancing factor for hypercholesterolemia.10,11However, the extent to which the relationship between HDP and CVD events is mediated by these established CVD risk factors remains less clear. Previous studies have examined the role of individual mediators, but no study has examined the joint contribution of chronic hypertension, hypercholesterolemia, T2DM, and BMI in mediating the relationship between HDP and CVD.5,12,13The American Heart Association has recognized gestational hypertension and preeclampsia as risk factors for CVD and encouraged clinicians to evaluate cardiovascular risk by screening women for these adverse pregnancy outcomes since 2011.14Longitudinal investigation of CVD incidence after a hypertensive pregnancy that examines the role of intermediate CVD risk factors is essential to inform screening practices and clinical recommendations for women with a history of HDP.
With up to over 50 years of follow-up after first birth and longitudinal collection of health-related behaviors, reproductive history, and incident CVD risk factors and events, we examined the association between HDP and CVD, controlling for prepregnancy confounders, and examined mediation by subsequent CVD risk factors—chronic hypertension, hypercholesterolemia, T2DM, and changes in BMI—in the NHSII (Nurses’ Health Study II).
Methods
Cohort description
The NHSII is an ongoing cohort of 116,429 female U.S. registered nurses aged 25-42 years at enrollment in 1989. Participants are followed prospectively through biennial questionnaires, which ascertain information on health-related behaviors, medication use, and incident disease. The average active follow-up rate for each questionnaire is >90%. This study protocol was approved by the Institutional Review Boards of Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health (protocol number: 1999P003389).
Hypertensive disorders of pregnancy
The 2009 biennial questionnaire captured complete pregnancy history, including adverse pregnancy outcomes and gestation length. Participants self-reported HDP as “pregnancy-related high blood pressure” (gestational hypertension) or “preeclampsia/toxemia.” Since this questionnaire did not ascertain chronic hypertension during pregnancy, the analysis focused on new-onset hypertension in pregnancy (gestational hypertension and preeclampsia). A validation study among 462 NHSII participants who self-reported preeclampsia on biennial questionnaires from 1991 to 2001 demonstrated that 89% had medical record evidence of preeclampsia.10The primary analysis focused on HDP in first pregnancy (normotension [ref], gestational hypertension, preeclampsia) because HDP predominantly occurs during first pregnancies15and to avoid potential bias induced by selective fertility (wherein the decision to pursue subsequent pregnancies is dependent on previous pregnancy outcomes).16A secondary analysis examined HDP exposure across all lifetime pregnancies, including ever and recurrent HDP (see theSupplemental Appendixfor details).
CVD events
Participants reported history of physician-diagnosed “myocardial infarction (MI) or angina” or “stroke (cerebrovascular accident) or transient ischemic attack” on the 1989 baseline questionnaire. Subsequent biennial questionnaires captured incident CVD events. Participants or next of kin approved medical record access for validation of incident events. MI events were confirmed using the World Health Organization criteria of symptoms plus either diagnostic electrocardiographic results or elevated cardiac-specific enzymes.17,18Fatal coronary artery disease (CAD) events were confirmed using hospital records, autopsy, or death certificates among individuals with evidence of prior CAD. Stroke was confirmed using National Survey of Stroke criteria, requiring neurological deficit with rapid or sudden onset that persisted for >24 hours or until death.19Strokes discovered through radiological imaging alone and cerebrovascular pathology resulting from infection, trauma, or malignancy (“silent” strokes) were not included. CVD events, including CAD (MI or fatal CAD) and stroke, that satisfied these criteria upon medical record review were considered definite. CVD events for which medical records could not be obtained or for which permission was not granted but were confirmed by the participant or a relative were considered probable. Definite and probable CVD cases comprised the outcome of interest.
Covariates
In 1989, participants reported race/ethnicity, current height and weight, weight at age 18 years, physical activity, parental history of MI before age 60 years, medical history (including chronic hypertension and diabetes not during pregnancy), and history of smoking, alcohol consumption, and oral contraceptive use. Biennial questionnaires after 1989 updated health-related behaviors and additionally ascertained diet, an expanded personal medical history (including hypercholesterolemia), and the nurse’s parents’ education level, history of stroke before age 60 years, and ages at and causes of death.
BMI (kg/m2) was calculated from height and weight at age 18 years and at each biennial questionnaire. For ages at which weight was not reported, BMI was derived based on reported weights and incorporating somatograms at ages 20, 30, and 40 years.10Diet was summarized in quintiles using the 2010 Alternative Healthy Eating Index dietary quality score, derived from food frequency questionnaires.20Self-reported weight at age 18 years, current height, diet, and physical activity have been shown to be reliable in previous validation studies (see theSupplemental Methods). Prepregnancy information was drawn from the biennial questionnaire immediately before the first pregnancy. Because most first pregnancies (83%) occurred before NHSII enrollment, information about health-related behavior in high school and within varying age ranges from 13 through 42 years reported at baseline was used to assign prepregnancy values for women with first births before 1989.
Hypercholesterolemia was defined as self-report of hypercholesterolemia or cholesterol-lowering medication use (collected since 1999). Incident diabetes was confirmed through a supplemental questionnaire, which collected information on symptoms, diagnostic tests, and treatment. Diabetes cases were classified into categories established by the National Diabetes Data Group and American Diabetes Association, as described elsewhere.21-23Participants reported the year of diagnosis for incident physician-diagnosed conditions within 3 categories. For chronic hypertension and hypercholesterolemia, the midpoint of each date range was used as the year of diagnosis. For T2DM, year of diagnosis came from the supplemental questionnaire. Medical record validation has previously demonstrated the accuracy of nurse participants’ self-report of chronic hypertension (sensitivity: 94%), hypercholesterolemia (confirmation: 86%), and T2DM (confirmation: ≥98%).24-26
Exclusions
Analyses were restricted to women who completed the 2009 biennial questionnaire, which permitted dating of first birth and assignment of HDP exposure (n = 76,840). After applying additional exclusion criteria (Figure 1), 60,379 parous women free of CVD before first pregnancy were retained in the primary analysis. For the mediation analysis, we further restricted to 57,974 women at risk for the potential mediators of interest. The analysis of lifetime HDP started follow-up at age 40 years (by which point 95% of women had experienced their final pregnancy) and was restricted to 57,137 parous women with their final pregnancy before age 40 years and who remained free of CVD at age 40 years.
Figure 1
Flow Diagram for the Primary, Mediation, and Secondary Analyses
∗Women reporting chronic hypertension within 1 year after first birth (n = 115) were excluded to prevent misclassification of exposure (undetected chronic hypertension before pregnancy may be incorrectly captured as incident chronic hypertension directly following pregnancy) and because the exact date of diagnosis was unknown, which prevented definitive determination as to whether the chronic hypertension arose before, during, or after pregnancy. CVD = cardiovascular disease; HDP = hypertensive disorders of pregnancy.
Statistical analysis
Characteristics of the analytic population at first pregnancy and at 1989 NHSII enrollment were standardized to the age distribution of the population and summarized by HDP status in first pregnancy (Table 1). Cox proportional hazards models estimated HRs and 95% CIs for the association between HDP and CVD. Women contributed person-time to the analysis from first birth until confirmed CVD, death, last returned questionnaire, or 2017 (Figure 2).
Table 1 Age-Standardized Characteristics of Nurses’ Health Study II Participants by Hypertensive Status at First Pregnancy
Hypertensive Disorder in First Pregnancy Status
Normotensive Pregnancy (n = 54,756, 90.7%)
Gestational Hypertension (n = 1,789, 3.0%)
Preeclampsia (n = 3,834, 6.4%)
Age at first birth, ya
27.0 ± 4.6
28.2 ± 4.9
27.0 ± 4.8
Age at NHSII enrollment (1989), ya
35.1 ± 4.7
34.3 ± 4.7
34.5 ± 4.6
Nulliparous at NHSII enrollment
16
18
16
Race/ethnicity
White
94
95
94
Black
1
1
1
Hispanic/Latina
2
1
2
Asian
1
1
1
Other/Multiracial
2
2
2
Participant mother’s education >12 y
32
32
32
Participant father’s education >12 y
38
35
38
Strenuous physical activity, at ages 18-22 y
Never
28
29
27
10-12 months/y
11
11
11
Prepregnancy body mass index, kg/m2
21.8 ± 3.5
23.3 ± 4.4
22.9 ± 4.2
Prepregnancy body mass index ≥30 kg/m2
2
7
6
Prepregnancy type 2 diabetes mellitusb
<1
0
0
Prepregnancy hypercholesterolemia
3
3
4
Parental history of MI/fatal CAD or stroke before age 60 y
20
24
24
Alternative Healthy Eating Index scorec
Lowest quintile (unhealthy)
20
23
22
Highest quintile (healthy)
19
20
18
Prepregnancy smoking status
Never
68
70
68
Past
10
9
10
Current
22
21
22
Prepregnancy alcohol intake
None
26
27
28
≤1 drink/wk
37
36
36
2-6 drinks/wk
29
29
28
≥1 drink/d
8
8
8
Prepregnancy oral contraceptive use
Never
22
21
19
<2 y
25
26
27
2-<4 y
22
21
22
≥4 y
31
32
32
Preterm delivery (<37 wks) in first birth
8
8
16
Final parityd
1 birth
16
21
22
2 births
49
48
49
3 births
26
23
23
≥4 births
9
8
7
Figure 2
Nurses’ Health Study II Data Collection Timeline and Analytic Follow-Up
Ascertainment of exposure and assignment of prepregnancy covariate information for participants with their first birth before cohort enrollment and for those with their first birth during active follow-up. CVD = cardiovascular disease.
We compared the distributions of age at and time to CVD development between HDP groups using log-rank tests. Multivariable models were adjusted for variables identified a priori as prepregnancy confounding variables: age at first birth; age at NHSII enrollment; race/ethnicity; parental education; strenuous physical activity at ages 18-22 years; parental history of CVD before age 60 years; and prepregnancy BMI, alcohol consumption, diet, smoking, oral contraceptive use, and hypercholesterolemia. (As only 11 women developed T2DM before first pregnancy, this was not included in multivariable adjustment.) Models for lifetime HDP additionally adjusted for final parity. Missing covariate data were addressed by missing indicators. To evaluate nonlinear departures from proportional hazards, we used restricted cubic splines to conduct a nonparametric test of whether the HDP-CVD association was modified by time since first birth.27,28As no nonlinearity was revealed, we tested for linear departures through a likelihood ratio test, comparing nested models with and without multiplicative interaction terms between the following: 1) gestational hypertension and time since first birth; and 2) preeclampsia and time since first birth; no linear departures from proportional hazards were found(P =0.12). Multivariable-adjusted cumulative incidence curves for CVD were obtained at the mean and mode values of the continuous and categorical covariates, respectively, using the Breslow estimator.
To evaluate chronic hypertension, hypercholesterolemia, T2DM, and changes in BMI occurring after first pregnancy as potential mediators, we used the difference method, fitting models with and without these established CVD risk factors.29Chronic hypertension, hypercholesterolemia, and T2DM were treated as time-dependent binary mediators and, once a woman developed a mediator, she was considered to have the mediator through end of follow-up. BMI was treated as a time-varying continuous mediator, updated over follow-up according to self-reported changes in weight. Mediation analysis requires the following assumptions: 1) no unmeasured exposure-outcome confounding; 2) no unmeasured mediator-outcome confounding; 3) no unmeasured exposure-mediator confounding; and 4) no mediator-outcome confounder affected by the exposure.30To control for confounding of these relationships, we additionally adjusted for updated behaviors over follow-up in mediation models. We tested for the presence of interactions between each mediator and HDP using likelihood ratio tests of nested models with and without the interactions; no exposure-mediator interactions were found (allP> 0.05). We used the SAS %mediate macro to calculate the proportion of the HDP-CVD jointly mediated by chronic hypertension, T2DM, hypercholesterolemia, and BMI.31,32Several sensitivity analyses were conducted to examine the robustness of our findings (Supplemental Appendix). All analyses were conducted using SAS 9.4 (SAS Institute, Inc).
Results
Approximately 10% of women experienced HDP in their first pregnancy. First births occurred between 1964 and 2008 at an average age of 27.0 ± 4.7 years. Women with HDP in first pregnancy were similar to those with normotensive first pregnancies in demographics and health-related behaviors (Table 1). However, women with HDP were >3 times as likely to have a prepregnancy BMI ≥30 kg/m2and were more likely to have a parent with a premature CVD event.
By the end of follow-up, when participants were a median age of 61 years (IQR: 57-64 years; range 33-71 years) with a median follow-up of 34 years since first birth (IQR: 29-40 years; range 2-54 years), 1,074 (1.8%) women had experienced a first CVD event—560 CAD events (554 MIs and 6 fatal CAD) and 515 strokes (n = 1 woman had both an MI and stroke). In fully adjusted models, women with HDP in first pregnancy had a 63% increased rate of CVD compared with women with a normotensive first pregnancy (95% CI: 1.4-1.9) (Table 2, Model 2). Adjustment for prepregnancy BMI, smoking, and parental history of CVD accounted for most of the modest attenuation between age, race/ethnicity, and parental education-adjusted and fully adjusted estimates. When we separately examined gestational hypertension and preeclampsia with CAD and stroke endpoints, there were significant associations between preeclampsia and CAD (HR: 2.2; 95% CI: 1.7-2.8) and gestational hypertension and stroke (HR: 1.6; 95% CI: 1.0-2.4) (Central Illustration). Further adjustment for updated smoking, diet, alcohol intake, physical activity, and oral contraceptive use after pregnancy resulted in slight attenuation but did not alter conclusions (data not shown). Women with HDP in first pregnancy exhibited elevated rates of CVD relative to women with normotensive first pregnancies, regardless of gestation length (Table 3).
Table 2 Hypertensive Disorders in First Pregnancy and Cardiovascular Disease
Hypertensive Disorder in First Pregnancy Status
Normotensive Pregnancy (n = 54,756, 90.7%)
Gestational Hypertension (n = 1,789, 3.0%)
Preeclampsia (n = 3,834, 6.4%)
Hypertensive Disorders of Pregnancy (n = 5,623, 9.3%)
CVD (CAD or stroke)
Cases/person-y
920/1,885,474
41/57,900
113/128,840
154/186,740
Excess cases per 100,000 person-y
—
22
39
34
Median age at event (IQR), ya
56 (50-62)
58 (52-63)
55 (47-60)
56 (48-62)
Median time to event (IQR), ya
35 (29-40)
32 (27-37)
34 (29-39)
33 (28-38)
Model 1
1.00 (ref)
1.55 (1.13-2.12)
1.87 (1.54-2.28)
1.78 (1.50-2.11)
Model 2
1.00 (ref)
1.41 (1.03-1.93)
1.72 (1.42-2.10)
1.63 (1.37-1.94)
CAD
Cases/person-y
467/1,831,185
19/56,130
74/125,080
93/181,210
Excess cases per 100,000 person-y
—
8
34
26
Median age at event (IQR), ya
56 (51-61)
61 (55-65)
55 (47-61)
57 (50-62)
Median time to event (IQR), ya
34 (28-39)
31 (26-36)
33 (28-38)
32 (27-37)
Model 1
1.00 (ref)
1.42 (0.90-2.25)
2.42 (1.90-3.10)
2.12 (1.70-2.65)
Model 2
1.00 (ref)
1.27 (0.80-2.02)
2.21 (1.73-2.84)
1.93 (1.54-2.41)
Stroke
Cases/person-y
454/1,831,172
22/56,133
39/125,045
61/181,178
Excess cases per 100,000 person-y
—
14
6
9
Median age at event (IQR), yb
57 (50-62)
56 (52-62)
54 (48-60)
55 (48-61)
Median time to event (IQR), yb
34 (28-39)
31 (26-36)
33 (28-38)
32 (27-37)
Model 1
1.00 (ref)
1.67 (1.09-2.56)
1.29 (0.93-1.80)
1.41 (1.08-1.84)
Model 2
1.00 (ref)
1.56 (1.01-2.40)
1.21 (0.87-1.68)
1.32 (1.00-1.73)c
Central Illustration
Differential Associations by Hypertensive Disorder of Pregnancy and Cardiovascular Disease Subtypes
HRs and 95% CIs were obtained from fully adjusted Cox proportional hazards models (
Table 2, Model 2). The overall association between having a hypertensive disorder in first pregnancy and long-term maternal cardiovascular disease appeared to be driven by underlying associations between preeclampsia and coronary artery disease and between gestational hypertension and stroke.
Table 3 Hypertensive Disorders in First Pregnancy and Cardiovascular Disease by Gestation Length
CVD (CAD or Stroke)
HDP and Gestational Length at Delivery Status
Term (≥37 wks)
Preterm (<37 wks)
Normotensive Pregnancy (n = 50,404, 83.5%)
Gestational Hypertension (n = 1,643, 2.7%)
Preeclampsia (n = 3,216, 5.3%)
HDP (n = 4,859, 8.1%)
Gestational Hypertension (n = 146, 0.2%)
Preeclampsia(n = 618, 1.0%)
HDP (n = 764, 1.3%)
Cases/person-y
820/1,737,169
40/53,413
95/109,544
135/162,957
1/4,487
18/19,296
19/23,783
Excess cases per 100,000 person-y
—
28
40
36
a
46
33
Model 1
1.00 (ref)
1.69 (1.23-2.33)
1.89 (1.53-2.34)
1.83 (1.52-2.19)
a
2.21 (1.39-3.53)
1.88 (1.19-2.96)
Model 2
1.00 (ref)
1.53 (1.11-2.11)
1.74 (1.40-2.15)
1.67 (1.39-2.01)
a
2.04 (1.27-3.25)
1.74 (1.10-2.75)
Women with HDP in first pregnancy also developed CVD slightly younger and sooner after their first birth than women with normotensive first pregnancies (Table 2). The increased rate of CVD among women with HDP in first pregnancy became statistically significant between 40-49 years of age, ranging between a 41% and 81% increased rate through age 69 years (Supplemental Table 1). Women with HDP exhibited a higher cumulative incidence of CVD that emerged approximately 10 years after first birth for women with preeclampsia and 30 years after first birth for women with gestational hypertension (Figure 3).
Figure 3
Multivariable-Adjusted Cumulative Incidence of Cardiovascular Disease
Curves were obtained at the mean and mode values of the following continuous and categorical covariates, respectively: age at first birth; age at Nurses’ Health Study II enrollment; race/ethnicity; parental education; physical activity at ages 18-22 years; parental history of cardiovascular disease age <60 years; and prepregnancy smoking, body mass index, alcohol consumption, Alternative Healthy Eating Index score, oral contraceptive use, and hypercholesterolemia.
In total, 12% of women experienced at least 1 lifetime pregnancy characterized by HDP, and 2.2% (n = 1,265) experienced recurrent HDP (Table 4). Ever experiencing HDP was associated with a 63% higher rate of CVD (95% CI: 1.4-1.9) compared with women without HDP(Table 4, Model 3). Women with 1 pregnancy complicated by HDP had a 48% higher rate of CVD (95% CI: 1.2-1.8), and women with 2 or more HDP pregnancies had a 2.3-fold higher rate (95% CI: 1.7-3.1) compared with women with all normotensive pregnancies. Women with a history of 1 or more HDP pregnancies exhibited higher rates of CVD regardless of which pregnancies were complicated by HDP, although the highest relative risk was observed among women with recurrent HDP that affected their first and then a second or later pregnancy (HR: 2.5; 95% CI: 1.8-3.3).
Table 4 Ever and Recurrent Hypertensive Disorders of Pregnancy and Cardiovascular Disease
Pregnancy History at Age 40 y
n (%)
Cases/Person-y
HR (95% CI)
Model 1
Model 2
Model 3
Ever HDPa
6,639 (11.6)
180/137,586
1.78 (1.52-2.10)
1.63 (1.38-1.92)
1.63 (1.39-1.92)
Number of HDP Pregnancies
0
50,498 (88.4)
824/1,084,133
1.00 (ref)
1.00 (ref)
1.00 (ref)
1
5,374 (9.4)
132/111,825
1.61 (1.34-1.94)
1.48 (1.23-1.79)
1.48 (1.23-1.78)
2+
1,265 (2.2)
48/25,761
2.53 (1.89-3.39)
2.26 (1.68-3.04)
2.28 (1.70-3.07)
First Pregnancy
Second or Later Pregnancies
Normotensive
All Normotensive
42,397 (74.2)
670/906,026
1.00 (ref)
1.00 (ref)
1.00 (ref)
Normotensive
No Further Pregnancies
8,101 (14.2)
154/178,107
1.25 (1.04-1.49)
1.19 (0.99-1.42)
1.15 (0.96-1.39)
Normotensive
Any HDP
1,336 (2.3)
38/28,147
1.80 (1.30-2.50)
1.65 (1.19-2.29)
1.67 (1.20-2.32)
HDP
All Normotensive
2,979 (5.2)
63/61,140
1.46 (1.13-1.89)
1.36 (1.05-1.77)
1.36 (1.05-1.76)
HDP
No Further Pregnancies
1,178 (2.1)
33/24,957
2.01 (1.41-2.85)
1.76 (1.23-2.51)
1.71 (1.20-2.45)
HDP
Any HDP
1,146 (2.0)
46/23,342
2.78 (2.06-3.74)
2.45 (1.81-3.32)
2.45 (1.81-3.31)
Comparing models for HDP and CVD with and without CVD risk factors developing after pregnancy, 63.8% (95% CI: 38.6%-83.2%;P <0.0001) of the association between HDP in first pregnancy and CVD was jointly mediated by the subsequent development of chronic hypertension, hypercholesterolemia, T2DM, and changes in BMI (Table 5). The proportion mediated (PM) by these factors was higher for gestational hypertension (PM = 83.8%) than preeclampsia (PM = 57.3%). All CVD risk factors contributed to mediation; however, chronic hypertension accounted for the largest individual proportion followed by changes in BMI, hypercholesterolemia, and T2DM. Chronic hypertension individually mediated 81% and 48% of the associations between gestational hypertension and preeclampsia with CVD, respectively. Among women with CVD events, 95% of those with gestational hypertension (n = 39 of 41) and 89% of those with preeclampsia (n = 101 of 113) developed chronic hypertension between first pregnancy and their CVD event.
Table 5 Mediation of the HDP-CVD Relationship by Chronic Hypertension, Hypercholesterolemia, Type 2 Diabetes, and BMI Changes
Hypertensive Disorder in First Pregnancy Status
Normotensive Pregnancy (n = 52,668, 90.9%)
Gestational Hypertension (n = 1,675, 2.9%)
Preeclampsia (n = 3,631, 6.3%)
Hypertensive Disorders of Pregnancy (n = 5,306, 9.2%)
Cases/person-y
752/1,676,801
37/50,326
95/112,328
132/162,654
Without mediators (total effect)
1.00 (ref)
1.52 (1.09-2.12)
1.73 (1.24-2.42)
1.67 (1.38-2.01)
With mediators (direct effect)a
1.00 (ref)
1.07 (0.77-1.49)
1.26 (0.90-1.77)
1.20 (1.00-1.45)
Proportion mediatedb(95% CI)
Ref
83.8% (3.6%-99.9%)
57.3% (24.2%-84.9%)
63.8% (38.6%-83.2%)
Individually mediated by:
Chronic hypertension
Ref
80.7% (6.1%-99.6%)
48.0% (21.9%-75.3%)
56.2% (35.2%-75.1%)
Hypercholesterolemia
Ref
19.2% (8.0%-39.2%)
15.3% (8.0%-27.4%)
16.2% (10.9%-23.4%)
Type 2 diabetes mellitus
Ref
13.1% (5.3%-29.0%)
9.1% (4.4%-18.0%)
10.1% (6.3%-15.7%)
Changes in BMI
Ref
30.4% (12.1%-58.1%)
23.0% (11.8%-40.2%)
24.8% (16.3%-35.8%)
Sensitivity analyses
Sensitivity analyses to address the potential for outcome misclassification, immortal person-time bias, survival bias, and unmeasured confounding, and to examine an alternative method for handling missing data (multiple imputation by chained equations) did not materially alter the results (Supplemental Appendix,Supplemental Tables 2 and 3).
Discussion
Women with HDP in first pregnancy had a 63% higher rate of future CVD events compared with women with normotension, even after accounting for important shared risk factors, including prepregnancy BMI, smoking, and parental history of CVD. This elevated rate was largely explained by subsequent development of established CVD risk factors—chronic hypertension, hypercholesterolemia, T2DM, and changes in BMI—in the years after a hypertensive first pregnancy. The HDP-CVD relationship appeared to be driven by associations between preeclampsia and CAD and between gestational hypertension and stroke.
This study deepens our understanding of the relationship between HDP and long-term maternal CVD and highlights targets for potential risk reduction. Previous studies, largely unadjusted for prepregnancy cardiometabolic confounding factors, suggested an increased CVD risk of 1.7- to 2.7-fold in women with a history of HDP, depending on the specific exposure and outcome of interest, length of follow-up, and degree of adjustment.1The longitudinal nature of the NHSII permitted thorough adjustment for prepregnancy risk factors; yet, inclusion of prepregnancy demographic and behavioral variables only slightly attenuated HRs for the relationship between HDP and CVD. We found that 64% of the increased CVD risk associated with HDP was explained by subsequent development of chronic hypertension, hypercholesterolemia, T2DM, and changes in BMI. The fact that chronic hypertension accounted for much of this association is consistent with previous mediation analyses.5,12,13For example, an analysis among 220,024 women with a mean age of 57 years at baseline and followed for a median of 7 years in the UK Biobank found that chronic hypertension accounted for 64% of the increased risk of CAD among women with a history of HDP.13The large degree of mediation observed in the HDP-CVD relationship may also partially explain why including HDP in an established CVD risk score does not appear to improve CVD prediction in women ≥40 years of age.33
NHSII participants were followed for a median of 34 years after first birth and provided a complete reproductive history, which allowed examination of CVD risk associated with HDP exposure in any pregnancy. Although history of HDP in any pregnancy increased a woman’s risk of CVD relative to women without HDP, recurrent HDP in 2 or more pregnancies was associated with a more than doubling of CVD risk—findings consistent with those from the Swedish Medical Birth Register.34
Much of the previous literature has focused on preeclampsia or examined the hypertensive disorders jointly; with >60,000 parous women, we were able to examine gestational hypertension and preeclampsia separately, yielding informative differential relationships. Women with a history of preeclampsia in first birth had an increased rate of CAD but not stroke, whereas the opposite was true for women with a history of gestational hypertension, which conferred an increased rate of stroke but not CAD. This finding is consistent with a growing understanding that the HDP subtypes may represent different disease phenotypes rather than a spectrum of severity. The suggestion that gestational hypertension might be more strongly linked to stroke than preeclampsia in our data is consistent with findings from the Northern Finland Birth Cohort 1966.4Further, our mediation findings demonstrated that chronic hypertension accounted for a greater proportion of the association between gestational hypertension and CVD than that between preeclampsia and CVD, and we previously found women with gestational hypertension to have a higher risk of developing chronic hypertension than women with preeclampsia.10Given these findings and the primacy of hypertension as a risk factor for stroke,35it is not surprising to see the association between gestational hypertension and stroke in the current analysis.
Although gestational hypertension appears to be a pure hypertensive phenotype, the pathophysiology underlying preeclampsia is more heterogeneous, stemming from abnormal placentation that results in endothelial dysfunction, systemic vascular impairment, vasoconstriction, and end-organ ischemia during pregnancy.36In the years and decades following delivery, women with a history of preeclampsia exhibit vascular endothelial dysfunction, changes to cardiac structure and function, and increased premature vascular aging and subclinical atherosclerosis.36-41Endothelial dysfunction may serve as a shared risk factor for both preeclampsia and CAD via inadequate vascularization of the uterus during pregnancy and of the myocardium later in life.40
Study limitations
The primary study limitation is the potential for exposure misclassification, given nurse participants’ self-reported HDP. However, an NHSII validation study confirmed medical record evidence of preeclampsia for the majority of women who reported it. Although HDP additionally includes chronic hypertension and superimposed preeclampsia,42this analysis focused on new-onset hypertension during pregnancy (gestational hypertension and preeclampsia), which is consistent with existing HDP-CVD literature.1Although we cannot rule out the potential for residual or unmeasured confounding (such as by social determinants of health), this study provides the most complete prepregnancy covariate adjustment currently available. Further, based on the calculated E-values, an unmeasured confounder would need to be associated with both HDP and CVD by a magnitude of 2.0- to 3.9-fold above and beyond the measured variables included in the model to explain away the observed associations. The only measured confounder within that range was prepregnancy obesity (HR: 2.4; Model 2 for HDP-CVD), so it is unlikely that the observed associations were caused by an unmeasured confounder. Finally, NHSII participants are predominantly White nurses, and our findings should be generalized to other populations with some caution. In particular, non-Hispanic Black women have higher risks of HDP and CVD, relative to non-Hispanic White women, and rates of preeclampsia are increasing more rapidly among Black women than White women43; yet, it remains to be seen whether the magnitude of the HDP-CVD association differs among these and other women of color.
Women who develop HDP typically exhibit a subtle adverse cardiovascular risk profile before pregnancy, as demonstrated in this and previous studies.44Although this suggests the CVD risk trajectory precedes pregnancy, the experience of HDP itself may also induce vascular, endothelial, or organ damage that directly increases a woman’s risk of CVD.45,46However, regardless of whether the HDP-CVD relationship is causal, HDP has the potential to be a powerful clinical risk marker. The “stress test” of pregnancy may help alert women and their providers to their underlying cardiovascular risk, creating an opportunity for primordial prevention of CVD risk factors.43,47,48To leverage this window of opportunity, however, bridges need to be established between obstetric and primary care for risk communication, behavioral intervention, and follow-up; primary care providers and cardiologists should also be sure to obtain reproductive histories from their patients.
Conclusions
To our knowledge, this study presents the most complete control of prepregnancy confounding in the relationship between HDP and long-term CVD and is the first to estimate the proportion of this association jointly mediated by chronic hypertension, hypercholesterolemia, T2DM, and changes in BMI. Even after adjustment for prepregnancy confounders, HDP in first pregnancy remained associated with a 63% higher rate of CVD later in life. Over 80% of the increased risk of CVD among women with gestation hypertension was accounted for by the development of chronic hypertension after pregnancy. Although the majority of the preeclampsia-CVD association was jointly explained by established CVD risk factors, approximately 40% of the association remained unexplained; this suggests that preeclampsia may increase the risk of CVD through nontraditional and/or under-recognized risk factors. Our findings suggest that screening for and treatment of chronic hypertension, hypercholesterolemia, T2DM, and overweight/obesity following a pregnancy may delay, or even prevent, cardiovascular disease among women with a history of HDP.
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At Cross County Cardiology - Mt. Sinai, we strive to keep you healthy, not only now, but in your future too. And as it pertains to our female patients looking ahead to the birth a child(s), it's very important to us that both you and your baby are doing what you can to minimize hypertension during pregnancy. This is why we asked Dr. Christopher Pumill to give us his input on this article.
Dr. Christopher Pumill says, "Women who have hypertensive disorders during pregnancy (ex: gestational hypertension, pre-eclampsia, eclampsia) is associated development of cardiovascular disease long-term. In fact, women who had a hypertensive pregnancy disorder had a 60% increase in risk of developing cardiovascular disease than normotensive patients. In the setting of this increased risk, its prudent to closely monitor and manage all other traditional risk factors of CVD (hypertension, high cholesterol, diabetes, metabolic syndrome, etc)."
So take it from the best heart experts in NJ and make sure to closely monitor both you and your baby's health. If you're feeling any symptoms, please just give us a call at 201-499-7361. We're here with you all the way!
Going on a low-carb diet has long been a popular weight loss strategy. But some doctors and nutrition experts have advised against doing so over fears that it could increase the risk of heart disease, since such diets typically involve eating lots of saturated fats, the kind found in red meat and butter.
But a new study, one of the largest and most rigorous trials of the subject to date, suggests that eating a diet low in carbohydrates and higher in fats may be beneficial for your cardiovascular health if you are overweight.
The new study, which waspublished in the American Journal of Clinical Nutrition, found that overweight and obese people who increased their fat intake and lowered the amount of refined carbohydrates in their diet — while still eating fiber-rich foods like fresh fruits, vegetables, nuts, beans and lentils — had greater improvements in their cardiovascular disease risk factors than those who followed a similar diet that was lower in fat and higher in carbs. Even people who replaced “healthy” whole grain carbs like brown rice and whole wheat bread with foods higher in fat showed striking improvements in a variety of metabolic disease risk factors.
The study suggests that eating fewer processed carbs while eating more fat can be good for yourheart health, said Dr. Dariush Mozaffarian, a cardiologist and dean of the Friedman School of Nutrition Science and Policy at Tufts University, who was not involved with the research. “I think this is an important study,” he said. “Most Americans still believe that low-fat foods are healthier for them, and this trial shows that at least for these outcomes, the high-fat, low-carb group did better.”
Still, Dr. Mozaffarian stressed, the types and balance of fats you eat also appear to be important. People on the low-carb diet consumed foods like butter, red meat and whole milk, which are rich in saturated fats. But most of the fat in their diets — about two thirds — was unsaturated, which is the kind of fat that is predominantly found in olive oil, avocados, nuts, seeds and fish.
“It’s a well controlled trial that shows that eating lower carb and more saturated fat is actually good for you, as long as you have plenty of unsaturated fats and you’re mostly eating a Mediterranean-type diet,” Dr. Mozaffarian added. Many doctors recommend a traditional Mediterranean style diet, rich in fruits and vegetables, fish and heart-healthy fats like nuts and olive oil, for cardiovascular health.Other rigorous studieshave found that following a Mediterranean diet can help to ward off heart attacks and strokes.
The new study included 164 overweight and obese adults, mostly women, and took part in two phases. First, the participants were put on strict, low-calorie diets that lowered their body weights by about 12 percent. Then they were each assigned to follow one of three diets in which 20 percent, 40 percent or 60 percent of their calories came from carbohydrates.
Protein was kept steady at 20 percent of calories in each diet, with the remaining calories coming from fat. The participants were fed just enough calories to keep their weights stable. The participants followed the eating plans for five months, with all of their meals provided to ensure that they stuck to their diets.
The average Americangets about 50 percent of his or her daily caloriesfrom carbs, most of them in the form of highly processed starchy foods like pastries, bread and doughnuts and sugary foods and beverages. In the new study, the low-carb group ate significantly fewer carbs than the average American. But they were not on a super-low-carb ketogenic diet, which severely restricts carbs to less than 10 percent of daily calories and forces the body to burn fat rather than carbohydrates. Nor did they eat unlimited amounts of foods high in saturated fats like bacon, butter and steak.
Instead, the researchers designed what they considered practical and relatively healthy diets for each group. All of the participants ate meals like vegetable omelets, chicken burritos with black beans, seasoned London broil, vegetarian chili, cauliflower soup, toasted lentil salads and grilled salmon. But the high-carb group also ate foods like whole wheat bread, brown rice, multigrain English muffins, strawberry jam, pasta, skim milk and vanilla yogurt. The low-carb group skipped the bread, rice and fruit spreads and sugary yogurts. Instead, their meals contained more high-fat ingredients such as whole milk, cream, butter, guacamole, olive oil, almonds, peanuts, pecans and macadamia nuts, and soft cheeses.
After five months, people on the low-carb diet did not experience any detrimental changes in their cholesterol levels, despite getting 21 percent of their daily calories from saturated fat. That amount is more than doublewhat the federal government’s dietary guidelines recommend. Their LDL cholesterol, the so-called bad kind, for example, stayed about the same as those who followed the high-carb diet, who got just 7 percent of their daily calories from saturated fat. Tests also showed that the low-carb group had a roughly 15 percent reduction in their levels of lipoprotein(a), a fatty particle in the blood that isstrongly linked to the development of heart disease and strokes.
The low-carb group also saw improvements in metabolic measures linked to the development of Type 2 diabetes. The researchers assessed their lipoprotein insulin resistance scores, or LPIR, a measure of insulin resistance that looks at the size and concentration of cholesterol-carrying molecules in the blood.Large studies have foundthat people with high LPIR scores are more likely to develop diabetes. In the new study, people on the low-carb diet saw their LPIR scores drop by 15 percent — reducing their diabetes risk — while those on the high-carb diet saw their scores rise by 10 percent. People on the moderate carb diet had no change in their LPIR scores.
The low-carb group had other improvements as well. They had a drop in their triglycerides, a type of fat in the blood that is linked to heart attacks and strokes. And they had increases in their levels of adiponectin, a hormone that helps to lower inflammation andmake cells more sensitive to insulin, which is a good thing. High levels of body-wide inflammation are linked to a range of age-related illnesses, including heart disease and diabetes.
The low-carb diet that was used in the study largely eliminated highly processed and sugary foods while still leaving room for “high quality” carbs from whole fruits and vegetables, beans, legumes and other plants, said Dr. David Ludwig, an author of the study and an endocrinologist at Harvard Medical School. “It’s mainly focused on eliminating the processed carbs, which many people are now recognizing are among the least healthful aspects of our food supply,” said Dr. Ludwig, who is co-director of the New Balance Foundation Obesity Prevention Center at Boston Children’s Hospital.
Dr. Ludwig stressed that the findings do not apply to the very-low carb levels typical of ketogenic diets, whichhave been shown to cause sharp elevationsin LDL cholesterol in some people. But he said the study does show that people can gain metabolic and cardiovascular benefits by replacing the processed carbs in their diets with fat, including saturated fat, without worsening their cholesterol levels.
The new study cost $12 million and was largely funded by the Nutrition Science Initiative,a nonprofit research group. It was also supported by grants from the National Institutes of Health, the New Balance Foundation and others.
Linda Van Horn, a nutrition expert who served on the federal government’s dietary guidelines advisory committee and who was not involved with the new study, noted that the low-carb group consumed large amounts of unsaturated fat and fiber-rich vegetables — both of which are known to have beneficial effects on cholesterol and cardiovascular risk markers. The low-carb group, for example, consumed an average of 22 grams of fiber per day, which is more than the average American consumes, she said.
“While the study is valuable and carefully designed, as always innutrition research, there are many dietary factors that influence cardiometabolic risk factors that can help to explain the results,” said Dr. Van Horn, who is also chief of nutrition in the department of preventive medicine at the Northwestern University Feinberg School of Medicine.
Dr. Mozaffarian said his take home message for people is to adopt what he calls a high-fat Mediterranean style diet. It entails eating fewer highly-processed carbs and sugary foods and focusing on fruits, vegetables, nuts, seeds, fish, cheese, olive oil and fermented dairy products like yogurt and kefir. “That’s the diet that America should be focusing on. It’s where all the science is converging,” he said.
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The physicians at Cross County Cardiology - Mt. Sinai are here to help you take care of your health. Make an appointment today by calling 201-776-8690 or go online to schedule. Your heart will thank you!
Despite increasing popularity of electronic cigarettes (e-cigarettes), the long-term health effects of habitual e-cigarette use remain unclear.1Many constituents of e-cigarette aerosols, including nicotine, carbonyl compounds, fine particulate matter, and metals, are associated with substantial toxicity.1Inhalation of e-cigarette aerosols among young, healthy adults induces inflammation and oxidative stress.1Two large cross-sectional studies reported no significant association between exclusive e-cigarette use and cardiovascular disease (CVD).2,3However, longitudinal studies are essential to assess the association of e-cigarette use with incident CVD.
Authors say fitness checks should join other, more commonly measured risk factors, given its strong prognostic value.
Cardiorespiratory fitness and age are the two most important variables for predicting all-cause mortality in patients with coronary artery disease, a new artificial intelligence (AI) study shows.
Cardiac complications, particularly myocarditis and pericarditis, have been associated with SARS-CoV-2 (the virus that causes COVID-19) infection (1–3) and mRNA COVID-19 vaccination (2–5). Multisystem inflammatory syndrome (MIS) is a rare but serious complication of SARS-CoV-2 infection with frequent cardiac involvement (6). Using electronic health record (EHR) data from 40 U.S. health care systems during January 1, 2021–January 31, 2022, investigators calculated incidences of cardiac outcomes (myocarditis; myocarditis or pericarditis; and myocarditis, pericarditis, or MIS) among persons aged ≥5 years who had SARS-CoV-2 infection, stratified by sex (male or female) and age group (5–11, 12–17, 18–29, and ≥30 years). Incidences of myocarditis and myocarditis or pericarditis were calculated after first, second, unspecified, or any (first, second, or unspecified) dose of mRNA COVID-19 (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) vaccines, stratified by sex and age group. Risk ratios (RR) were calculated to compare risk for cardiac outcomes after SARS-CoV-2 infection to that after mRNA COVID-19 vaccination. The incidence of cardiac outcomes after mRNA COVID-19 vaccination was highest for males aged 12–17 years after the second vaccine dose; however, within this demographic group, the risk for cardiac outcomes was 1.8–5.6 times as high after SARS-CoV-2 infection than after the second vaccine dose. The risk for cardiac outcomes was likewise significantly higher after SARS-CoV-2 infection than after first, second, or unspecified dose of mRNA COVID-19 vaccination for all other groups by sex and age (RR 2.2–115.2). These findings support continued use of mRNA COVID-19 vaccines among all eligible persons aged ≥5 years.
This study used EHR data from 40 health care systems* participating in PCORnet, the National Patient-Centered Clinical Research Network (7), during January 1, 2021–January 31, 2022. PCORnet is a national network of networks that facilitates access to health care data and interoperability through use of a common data model across participating health care systems (https://pcornet.org/dataexternal icon). The PCORnet Common Data Model contains information captured from EHRs and other health care data sources (e.g., health insurance claims), including demographic characteristics, diagnoses, prescriptions, procedures, and laboratory test results, among other elements. The study population included persons with documented SARS-CoV-2 testing, viral illness diagnostic codes, or COVID-19 vaccination during the study period. Data were obtained through a single query that was executed by participating health care systems to generate aggregated results.
Five cohorts were created using coded EHR data among persons aged ≥5 years: 1) an infection cohort (persons who received ≥1 positive SARS-CoV-2 molecular or antigen test result); 2) a first dose cohort (persons who received a first dose of an mRNA COVID-19 vaccine); 3) a second dose cohort (persons who received a second dose of an mRNA COVID-19 vaccine); 4) an unspecified dose cohort (persons who received an mRNA COVID-19 vaccine dose not specified as a first or second dose); and 5) an any dose cohort (persons who received any mRNA COVID-19 vaccine dose). The any dose cohort is a combination of the other three vaccination cohorts; persons who received 2 doses were included twice in this cohort, once for each dose.†Vaccine doses specifically coded as booster or extra doses were excluded. Persons with a positive SARS-CoV-2 test result ≤30 days before receipt of an mRNA COVID-19 vaccine were excluded from the vaccine cohorts; persons who had received an mRNA COVID-19 vaccine dose ≤30 days before a positive SARS-CoV-2 test result were excluded from the infection cohort. In the infection cohort, there were no other exclusions based on vaccination status. The following index dates were used for cohort entrance: first positive SARS-CoV-2 test result for the infection cohort; first vaccination for the first dose cohort; second vaccination for the second dose cohort; the single vaccination for the unspecific dose cohort; and the first, second, and unspecified vaccination for the any dose cohort. Persons could be represented twice in the any dose cohort if they received a first and second dose; they would have a different index date for each of the doses.
Incidence of three cardiac outcomes (myocarditis; myocarditis or pericarditis; and myocarditis, pericarditis, or MIS) were defined usingInternational Classification of Diseases, Tenth Revision, Clinical Modification(ICD-10-CM) diagnostic codes§within 7-day or 21-day risk windows after the index date; persons who had received any of these diagnoses during the year preceding the index date were excluded. The outcome including MIS was only assessed for the infection cohort because the rare reports of MIS after mRNA COVID-19 vaccination typically had evidence of previous SARS-CoV-2 infection (8); a 42-day risk window also was used for this outcome to allow for a possible long latency between infection and diagnosis of MIS (6).¶Because persons with MIS who have cardiac involvement might only receive an ICD-10-CM code for MIS, rather than myocarditis or pericarditis, this combined outcome allowed for a comprehensive capture of potential cardiac complications after infection. Nearly 80% of cases of MIS have cardiac involvement (9). Cohorts were stratified by sex and age group.
The sex- and age-stratified incidences of the cardiac outcomes (cases per 100,000 persons) were calculated within 7-, 21-, or 42-day risk windows. Unadjusted RRs and 95% CIs were calculated as the incidences of the outcomes within the infection cohort divided by the incidences in the first, second, unspecified, and any dose cohorts separately for each sex and age stratum. RRs whose CIs did not include 1.0 were considered statistically significant; RRs were not compared across outcomes, risk windows, vaccine dose, or sex and age stratum. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.**
The study population consisted of 15,215,178 persons aged ≥5 years, including 814,524 in the infection cohort; 2,548,334 in the first dose cohort; 2,483,597 in the second dose cohort; 1,681,169 in the unspecified dose cohort; and 6,713,100 in the any dose cohort (Table 1).††Among the four COVID-19 vaccination cohorts, 77%–79% of persons were aged ≥30 years; within the SARS-CoV-2 infection cohort, 63% were aged ≥30 years.
Among males aged 5–11 years, the incidences of myocarditis and myocarditis or pericarditis were 12.6–17.6 cases per 100,000 after infection, 0–4 after the first vaccine dose, and 0 after the second dose; incidences of myocarditis, pericarditis, or MIS were 93.0–133.2 after infection (Table 2). Because there were no or few cases of myocarditis or pericarditis after vaccination, the RRs for several comparisons could not be calculated or were not statistically significant. The RRs were significant when comparing myocarditis, pericarditis, or MIS in the 42 days after infection (133.2 cases per 100,000) with myocarditis or pericarditis after the first (4.0 cases per 100,000; RR 33.3) or second (4.7 cases per 100,000; RR 28.2) vaccine dose.
Among males aged 12–17 years, the incidences of myocarditis and myocarditis or pericarditis were 50.1–64.9 cases per 100,000 after infection, 2.2–3.3 after the first vaccine dose, and 22.0–35.9 after the second dose; incidences of myocarditis, pericarditis, or MIS were 150.5–180.0 after infection. RRs for cardiac outcomes comparing infected persons with first dose recipients were 4.9–69.0, and with second dose recipients, were 1.8–5.6; all RRs were statistically significant.
Among males aged 18–29 years, the incidences of myocarditis and myocarditis or pericarditis were 55.3–100.6 cases per 100,000 after infection, 0.9–8.1 after the first vaccine dose, and 6.5–15.0 after the second dose; incidences of myocarditis, pericarditis, or MIS were 97.2–140.8 after infection. RRs for cardiac outcomes comparing infected persons with first dose recipients were 7.2–61.8, and with second dose recipients, were 6.7–8.5; all RRs were statistically significant.
Among males aged ≥30 years, the incidences of myocarditis and myocarditis or pericarditis were 57.2–114.0 cases per 100,000 after infection, 0.9–7.3 after the first vaccine dose, and 0.5–7.3 after the second dose; incidences of myocarditis, pericarditis, or MIS were 109.1–136.8 after infection. RRs for cardiac outcomes among infected persons compared with first dose recipients were 10.7–67.2, and compared with second dose recipients, were 10.8–115.2; all RRs were statistically significant.
Among females aged 5–11 years, incidences of myocarditis and myocarditis or pericarditis were 5.4–10.8 cases per 100,000 after infection, and incidences of myocarditis, pericarditis, or MIS were 67.3–94.2 after infection (Table 3). No cases of myocarditis or pericarditis after vaccination were identified. The incidences of cardiac outcomes did not vary by age among females aged ≥12 years. In this group, the incidences of myocarditis and myocarditis or pericarditis were 11.9–61.7 cases per 100,000 after infection, 0.5–6.2 after the first vaccine dose, and 0.5–5.4 after the second dose; incidences of myocarditis, pericarditis, or MIS were 27.1–93.3 after infection. Among females aged ≥12 years, RRs for cardiac outcomes comparing infected persons with first dose recipients were 7.4–42.6, and with second dose recipients, were 6.4–62.9; all RRs were statistically significant.
Vasovagal syncope (VVS) is a common clinical condition with an estimated lifetime prevalence of 35% (1,2). Although VVS is not associated with an increased rate of mortality, there is a significant deterioration in the quality of life (QoL) in conjunction with the severity and frequency of recurrences (3,4). Existing pharmacological and nonpharmacological therapies for VVS have, if at all, a modest efficacy (5,6). Yoga is one of the most common forms of complementary and alternative medicine therapies and is increasingly being practiced worldwide. Yoga, an ancient Indian practice based on the principles of mind-body medicine, has been observed to have a beneficial effect in hypertension, atrial fibrillation, and postmyocardial infarction rehabilitation (7–9). Several studies have shown yoga to favorably modulate the autonomic system by balancing the central and peripheral sympathetic–parasympathetic drives (10). Mindful practice and meditation, both integral to yoga, help in reducing stress (11,12). VVS is a type of reflex syncope mediated by emotional or orthostatic stress and is associated with an increased and imbalanced autonomic activation (13). Recent studies have shown the benefit of yoga in patients with VVS (14,15). This randomized controlled trial (RCT) was conducted to assess the effectiveness of yoga as adjuvant therapy in patients with VVS.
Previous studies have shown reduced cardiovascular risk with increasing high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high concentrations of HDL-C. Thus, we aimed to study the gender-specific relation between very high HDL-C levels (>80, >100 mg/100 ml) and adverse cardiovascular outcomes and the genetic basis in the general population enrolled in the United Kingdom Biobank.
A total of 415,416 participants enrolled in the United Kingdom Biobank without coronary artery disease were included in this prospective cohort study, with a median follow-up of 9 years.
A high HDL-C level >80 mg/100 ml was associated with increased risk of all-cause death (Hazard ratio [HR] 1.11, confidence interval [CI] 1.03 to 1.20, p = 0.005) and cardiovascular death (HR 1.24, CI 1.05 to 1.46, p = 0.01) after adjustment for age, gender, race, body mass index, hypertension, smoking, triglycerides, LDL-C, stroke history, heart attack history, diabetes, eGFR, and frequent alcohol use (defined as ≥3 times/week) using Cox proportional hazard and Fine and Gray's subdistribution hazard models, respectively.
In gender-stratified analyses, such associations were only observed in men (all-cause death HR 1.79, CI 1.59 to 2.02, p <0.0001; cardiovascular death HR 1.92, CI 1.52 to 2.42, p <0.0001), but not in women (all-cause death HR 0.97, CI 0.88 to 1.06, p = 0.50; cardiovascular death HR 1.04, CI 0.83 to 1.31, p = 0.70). The findings persisted after adjusting for the genetic risk score comprised of known HDL-C–associated single nucleotide polymorphisms.
Very high HDL-C levels are associated with an increased risk of all-cause death and cardiovascular death among men but not in women in the general population free of coronary artery disease.
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At Cross County Cardiology, we care about you and helping you prevent cardiovascular issues and deaths. This is why we recommend annual checkups with one of our skilled and knowledgable doctors. Make an appointment today by calling 201-776-8690 or go online, it could just save your life!
Is the joint association of lipoprotein(a) [Lp(a)] and coronary artery calcification (CAC) with increased risk of atherosclerotic cardiovascular disease (ASCVD) independent? This study recently published by the American College of Cardiology takes a look.
Quick Takes
Lp(a) and CAC are independently associated with ASCVD risk of death, fatal and nonfatal MI, and stroke after adjusting for other risk factors including family history of MI and each other.
Lp(a) has little clinically relevant prognostic implication for guiding primary prevention therapy decisions when CAC is known.
A higher 10-year ASCVD incidence occurs in the Lp(a) 5th quintile when compared with Lp(a) quintiles 1-4, but only among participants with CAC ≥100.
In persons with CAC from 0 to <100, there was no difference in incident ASCVD when the Lp (a) was ≥50 mg/dL, the level at which Lp(a) is considered a risk-enhancing factor.
Methods:
Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis; n = 4,512) and DHA (Dallas Heart Study; n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and three CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor–adjusted Cox regression models. ASCVD events included ASCVD-related death, nonfatal myocardial infarction (MI), or fatal or nonfatal stroke.
Results:
Among MESA participants (61.9 years of age), 476 incident major ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.04-1.61; HR, 1.68; 95% CI, 1.30-2.16; and HR, 2.66; 95% CI, 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. The distribution of CAC scores was similar across quintiles of Lp(a) at about 50% CAC = 0, and 25% for 1-99 and ≥100. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR, 4.71; 95% CI, 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR, 1.31; 95% CI, 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS.
Conclusions:
Lp(a) and CAC are independently associated with ASCVD risk of death, fatal and nonfatal MI, and stroke and may be useful concurrently for guiding primary prevention therapy decisions.
Perspective:
Current national cholesterol management guidelines consider elevated Lp(a) level ≥50 mg/dL as a risk-enhancing factor, and recommend using the CAC score (≥100 or ≥75th percentile for age, sex, and race) measure to guide decisions regarding primary ASCVD prevention. While the relationship of Lp(a) and CAC score and ASCVD are independent and additive, there is minimal clinical value when the CAC score is known. But persons with concomitant Lp(a) and CAC elevation (≥50 mg/dL and ≥100 CAC, respectively) have a >20% cumulative ASCVD incidence (secondary prevention coronary heart disease risk equivalent) over 10 years. These levels justify high-intensity statin therapy, intensifying lifestyle modification, and the addition of aspirin.
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At CCC-Mt Sinai, our patients are monitored for their levels and we adjust therapy/treatment based on results. Give us a call at 201-499-7361 or go online so we can help to check your levels too!
