Greater Risk Of Cardiovascular Disease Mortality Research Articles

Abstract 4132159: Dietary Intake of Niacin and Risk of Cardiovascular Mortality in The Golestan Cohort Study

Introduction: Recent studies have linked niacin metabolism with vascular inflammation and cardiovascular disease (CVD); however, the association is still inconclusive regarding dietary intake, and the findings may not be generalizable to various populations. In this longitudinal study within a Middle Eastern population, we aimed to assess the relationship between dietary intake of B vitamins, including niacin, and the risk of CVD mortality. Methods: Our study utilized data from the Golestan Cohort Study, which has tracked 50,045 participants aged 40-75 years since 2004. We excluded subjects who reported extreme total energy intake or had a positive history of cancer, CVD, or diabetes at baseline. Vitamin B intake estimations including thiamin, riboflavin, niacin, pyridoxamine, folate, and cobalamin intake were derived from the baseline food frequency questionnaire, noting that supplement use was uncommon in this cohort. To adjust for calorie intakes, we employed the nutrient density method. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for cardiovascular mortality, using the lowest quintile of intake as the reference group for vitamins and adjusting for potential confounders. Results: We analyzed 42,456 subjects with a mean age of 51.5 ± 8.7 years at baseline. During 579,339 person-years of follow-up (median: 14.1 years), 3,065 CVD deaths were recorded. The median dietary intake of niacin was 25.3 mg/d (Recommended Dietary Allowance = 14-16 mg/d). We observed significant associations between niacin intake (HR Q5 vs. Q1 = 1.13, 95% CI = 1.01-1.26, P trend <0.05) and CVD mortality. When niacin was modeled as a continuous linear variable, it was associated with a greater risk of CVD mortality (HR = 1.05, 95% CI = 1.01-1.09) per 2 mg/1000Kcal/d increase. None of the other B vitamin intakes evaluated were associated with CVD mortality in this population. Conclusion: These findings suggest that among B vitamins, only dietary niacin intake was positively associated with CVD mortality. Further confirmation in larger studies is needed.

Distal ascending aortic dilatation portends a near 2-fold greater risk of cardiovascular mortality than proximal enlargement: results from 120,000 patients in a nationwide echocardiographic database

Abstract Background The management of thoracic aortic dilatation is clinically challenging and acute aortic dissection (AD) is under-recognised as a primary cause of death. Despite the majority of AD occurring in non-severely dilated aortas, absolute aortic diameter remains the most utilised criterion for adjudging preventative surgical correction. In order to improve outcomes and guide management, greater prognostic understanding is needed. Purpose We examined a nationwide echocardiographic dataset linked to mortality outcomes to determine how ascending thoracic aortic dilatation and its site affects cardiovascular disease (CVD) mortality over time. Methods The National Echocardiography Database Australia (NEDA) was examined for aortic dimensions at the sinuses of Valsalva (SoV), sinotubular junction (STJ) and ascending aorta (AscAo) in patients who had undertaken >1 echocardiographic study. Following separation of those who had undergone corrective aortic surgery, patients were stratified according to absolute aortic diameters and grouped as normal (<4cm), mild (4.0-4.5cm), moderate (4.5-5cm) and severely (>5cm) dilated at the prescribed thoracic aortic sites. Mortality data was then linked from the National Death Index (NDI). Results 398,905 echocardiographs from 121,115 patients with a mean age of 62.6±16.2 years were included. At the time of mortality data linkage, 38,681 (32%) had died, of whom 13,292 (34%) died from CVD causes and only 276 (0.007%) had aortic dissection recorded as their primary cause of death. Severe aortic dilatation at any site increased the likelihood of 10-year CVD mortality (29% vs. 15% in those with normal diameters; HR 3.00; CI 1.60-5.63; p<0.0001), with an incremental increase in the probability of CVD death when moving from the proximal to distal ascending aorta; 10-year CVD mortality at the SoV 26% (HR 1.93; CI 1.29-2.87; p<0.001), STJ 39% (HR 2.82; CI 1.64-4.86; p<0.001) and AscAo 44% (HR 4.74; CI 2.46-9.13; p<0.001) respectively (Figure 1). When examining those patients who had undergone corrective aortic surgery, the likelihood of 10-year CVD mortality was comparable to the population with normal aortic diameters (17 vs. 15%, HR 1.1; CI 0.9-1.36; p=0.3) (Figure 2). Conclusion Severe aortic dilatation increases the probability of 10-year cardiovascular mortality. Interestingly, there is an incremental increase in the likelihood of CVD mortality when moving from the proximal to distal ascending aorta, with severe AscAo dilatation conferring a near 2-fold greater risk of CVD mortality compared with severe SoV aneurysms. Additionally, surgical aortic intervention nearly normalises survival probability to the population with healthy aortic diameters. These results identify new considerations for prognostication, risk stratification and surgical guidance of aortic repair.CVD mortality by aortic dilatationCVD mortality after aortic intervention

The association of the platelet/high-density lipoprotein cholesterol ratio with self-reported stroke and cardiovascular mortality: a population-based observational study

BackgroundPrevious studies have shown that the relationship between high-density lipoprotein cholesterol (HDL-C) and stroke is controversial, and the association between the platelet/high-density lipoprotein cholesterol ratio (PHR), a novel marker for inflammation and hypercoagulability states, and stroke has not been established.MethodsThis study presents an analysis of cross-sectional data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES). Stroke history, HDL-C levels, and platelet counts were obtained during cross-sectional surveys. The PHR was calculated as the ratio of the number of platelets to HDL-C concentration. Weighted logistic regression was used to assess the associations of HDL-C and the PHR with stroke. Nonlinearity of this relationship was determined through restricted cubic splines (RCSs) and two-piecewise linear regression for identifying inflection points. Furthermore, Cox regression was utilized to prospectively analyze the associations of the PHR and HDL-C concentration with cardiovascular disease (CVD) mortality in stroke survivors.ResultsA total of 27,301 eligible participants were included in the study; mean age, 47.28 years and 50.57% were female, among whom 1,040 had a history of stroke. After full adjustment, the odds ratio (OR) of stroke associated with a per standard deviation (SD) increase in the PHR was estimated at 1.13 (95% confidence interval (CI): 1.03 − 1.24, P = 0.01), and the OR of stroke associated with a per SD increase in HDL-C was 0.95 (95% CI: 0.86–1.05, P = 0.30). The RCS indicated a nonlinear relationship for both variables (PPHR = 0.018 and PHDL-C = 0.003), and further piecewise linear regression identified inflection points at PHR = 223.684 and HDL-C = 1.4 mmol/L. Segmental regression indicated that in the PHR ≥ 223.684 segment, the estimated OR of stroke associated with a per-SD increase in the PHR was 1.20 (95% CI: 1.09 − 1.31, P < 0.001), while the association of stroke with HDL-C was not significant before or after the inflection point (P > 0.05). Furthermore, Cox regression and RCS showed that a per-SD increase in the PHR was linearly associated with a greater risk of CVD mortality among stroke survivors (HR: 1.14, 95% CI: 1.06 − 1.22, P < 0.001; nonlinear, P = 0.956), while HDL-C was not significantly associated with CVD mortality.ConclusionThe association between the PHR and stroke incidence exhibited a significant threshold effect, with an inflection point at 223.684. A PHR exceeding 223.684 was positively associated with stroke, while the association between HDL-C and stroke was not significant. Additionally, the PHR was positively and linearly associated with CVD mortality among stroke survivors.

Cognitive impairment assessed by Mini-Mental State Examination predicts all-cause and CVD mortality in Chinese older adults: A 10-year follow-up study.

Cognitive impairment (CI) has been demonstrated as a useful proxy measure of mortality in Western populations. However, the predictive value of CI in Chinese populations is unknown. We aimed to explore whether CI is independently associated with increased long-term all-cause and cardiovascular disease (CVD) mortality in Chinese older adults and the association of performance in specific MMSE sub-domains to subsequent mortality. A total of 4,499 older adults [mean (SD) age, 70.3(6.7) years] who received a sample investigation from 2011 to 2014 were followed up till 2021 for mortality. The Mini-Mental State Examination was used to assess cognitive function, and Cox's proportional hazard models were used to evaluate the effects of cognitive function on the risk of all-cause and CVD mortality. Demographic characteristics, lifestyle, and health status were included as covariates. During a 10-year follow-up, a total of 667 (14.8%) died. In the fully adjusted model, compared with cognitively normal participants with CI had a 1.33-fold [HR, 1.33; (95% CI, 1.10-1.61)] greater risk of all-cause mortality and a 1.45-fold [HR, 1.45; (95% CIs, 1.11-1.92)] greater risk of CVD mortality. After a similar multivariable adjustment, a per-SD increase in MMSE scores was associated with a reduced risk of all-cause mortality [HR, 0.85; (95% CI, 0.78-0.93)] and CVD mortality [HR, 0.74; (95% CI, 0.65-0.84)]. In the unadjusted model, MMSE sub-domains (apart from immediate recall) were associated with mortality. But only orientation and calculation and attention were still independently associated with all-cause and CVD mortality in a multivariable model. These findings confirmed that CI is a marker of all-cause and CVD mortality risk in Chinese older adults, independently of other commonly assessed risk factors, and some sub-domains of the MMSE may have stronger associations with mortality. Further research is needed to identify the mechanisms underlying the observed associations.

Abstract 13468: Dietary Intake of Minerals and Risk of Cardiovascular Mortality in the Golestan Cohort Study

Introduction: Several studies have linked cardiovascular disease (CVD) to dietary intake of a few minerals, although the link is still unclear, and the findings may not apply to various populations. In a prospective study in a Middle Eastern population, we aimed to assess the relationship between dietary intakes of calcium, selenium, zinc, iron, magnesium, and copper and the risk of CVD mortality. Methods: We used data from the Golestan Cohort Study, which has followed 50,045 participants aged 40-75 years since 2004. We excluded subjects reporting extreme intakes of total energy and a positive history of cancer, CVD, or diabetes at baseline. Mineral intake was estimated from the baseline food frequency questionnaire. Supplement use was not common in this population. Mineral intakes were adjusted by the nutrient density method. We used Cox proportional hazards models to estimate hazards ratio (HR) and 95% confidence intervals (CI) for cardiovascular mortality using the lowest quintile of intake as a reference group for each mineral with adjustment for potential confounders. Results: We analyzed 41,863 subjects that had a mean age of 51.5+8.7 years at baseline . During 579,339 person-years of follow-up (median: 14.1 Years), 3,065 (7.22%) participants died due to CVD. Calcium was the only mineral with a mean intake below the US Recommended Dietary Allowance. We observed significant associations between calcium intake (HR Q5 vs Q1 =0.82, 95% CI=0.73-0.93), selenium intake (HR Q5 vs Q1 =1.14, 95% CI=1.01-1.29), and CVD mortality (P-values &lt;0.05). We observed no statistically significant associations with zinc (HR Q5 vs Q1 =1.10, 95% CI=0.98-1.24), iron (HR Q5 vs Q1 =1.08, 95% CI=0.96-1.22), magnesium (HR Q5 vs Q1 =1.01, 95% CI=0.90-1.14), or copper (HR Q5 vs Q1 =1.11, 95% CI=0.99-1.26) intake and CVD mortality. When modeled as continuous linear variables, iron and copper intake were associated greater risk of CVD mortality (P-values&lt;0.05). Conclusion: Dietary calcium intake was associated with decreased, whereas selenium and possibly copper intake were associated with increased risk of CVD mortality in this Middle Eastern population.

Abstract 12463: Low-Density-Lipoprotein Cholesterol and Mortality Outcomes Among Healthy Older Adults Not Taking Lipid-Lowering Agents: A Cohort Study With 12,334 Participants

Introduction: Clinical uncertainty remains about the relationship between cholesterol levels and risk of death in older persons. Hypothesis: Lower low-density lipoprotein (LDL) cholesterol level was associated with a decreased mortality risk from cardiovascular disease (CVD) and an increased mortality risk due to non-CVD causes in primary prevention older populations. Methods: We examined the relationship between LDL cholesterol levels and mortality outcomes in a cohort of older individuals aged ≥65 years enrolled into a clinical trial. At baseline, participants had no diagnosed dementia, physical disability or CVD events, and were not taking lipid-lowering agents. Multivariable Cox proportional-hazards models were used to examine associations of LDL cholesterol with all-cause, CVD, cancer, and combined non-CVD/non-cancer mortality. Restricted cubic splines were used to depict non-linear relationships. Results: Among 12,334 participants included in this analysis [mean (SD) age: 75.2 (4.6) years; 54% females], who were followed for a median of 6.9 (5.7-8.0) years, 1250 (10%) died (24% due to CVD, 43% cancer, and 33% non-CVD/non-cancer). There was a U-shaped relation linking LDL cholesterol and all-cause mortality (nadir: 3.3mmol/L) and a curvilinear relation for other mortality outcomes. Each 1-mmol/L higher LDL cholesterol was associated with a lower risk of all-cause mortality (HR=0.91, 95% CI 0.85-0.98), cancer mortality (0.83, 0.74-0.94) and non-CVD/non-cancer mortality (0.81, 0.71-0.93), but a higher risk of CVD mortality (1.19, 1.03-1.38). Reduced risks of all-cause and non-CVD/non-cancer mortality were only significant in males and but not females (P values for sex interaction &lt;0.05). When deaths in the five years after baseline were excluded, the HRs for all-cause, cancer, non-CVD/non-cancer and CVD mortality were 1.03, 1.05, 0. 91 and 1.21 respectively (all P&gt;0.10). Conclusions: Higher LDL cholesterol is associated with a greater risk of CVD mortality in older adults. Reduced risks for non-CVD mortality were likely driven by reverse causality, evidenced by the absence of associations after excluding deaths that occurred within the initial five years of follow-up.

Abstract LB084: High cardiovascular disease mortality after central nervous system tumor diagnosis: Evidence from UK and USA population-based study

Abstract Background Accumulating data show cardiovascular disease (CVD) is a major cause of death in many cancer patients supporting cardio-oncology epidemiology and clinical studies. Although rare, patients diagnosed with brain and central nervous system (CNS) tumours have significant morbidity and mortality. Whether CVD is a major cause of death and if this differs by malignancy has not been comprehensively assessed. Methods We aimed to examine the risk of CVD mortality in patients diagnosed with malignant and non-malignant CNS tumours using cancer registry data in the UK and US. Analyses were conducted using Wales Cancer Registry, UK (Secure Anonymised Information Linkage, SAIL) for 8,743 patients diagnosed from 2000-2015 (54.9% of which died); and the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) for 188,526 patients diagnosed from 2005-2015 (40.0% of which died). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated for CVD cause of death (heart disease, cerebrovascular disease, hypertension, atherosclerosis, and aortic aneurysm/dissection) and adjusted for age, sex and calendar year compared to all Welsh and US residents. SMRs were stratified by tumour types (malignant and non-malignant tumours) and main histologic types (glioma and meningioma). Results CVD is the second major cause of death for CNS tumour patients in SAIL and SEER (9.5% &amp; 12.1%, respectively). Patients with malignant and non-malignant CNS tumours had excess CVD mortality compared with the general population (SAIL SMR=2.64, 95% CI=2.39-2.90, SEER SMR=1.38, 95% CI=1.35-1.42). Patients were more likely to die of CVD compared to the general population regardless of whether they were diagnosed with non-malignant meningiomas subtypes (SAIL SMR=3.13, 95%CI=2.73-3.57; SEER SMR=1.36, 95%CI=1.32-1.40) or malignant gliomas (SAIL SMR=2.08, 95%CI=1.46-2.88; SEER SMR=2.21, 95%CI=2.05-2.38). Patients diagnosed younger than 50 years of age had excess risk from CVD mortality compared to general population than those diagnosed at older ages (SAIL SMR=4.58, 95%CI=2.38-7.84, SEER SMR 2.03-95%CI=1.79-2.03). Patients had greater risk of CVD mortality within the first year after CNS tumour diagnosis in both SAIL and SEER (SMR=2.98, 95% CI=2.39-3.66 &amp; SMR=2.14 95%CI=2.03-2.25, respectively). Conclusion CVD mortality is high among patients diagnosed with CNS tumours compared to general population. Cross national datasets for different histologic types of CNS tumours could help define high risk groups that may be targeted for future prevention and clinical studies to clarify the aetiology of CVD among CNS cancer patients. Citation Format: KAI JIN, Paul Brennan, Michael Poon, Cathie Sudlow, Jonine FIGUEROA. High cardiovascular disease mortality after central nervous system tumor diagnosis: Evidence from UK and USA population-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB084.

Long-term cardiovascular disease mortality among 160 834 5-year survivors of adolescent and young adult cancer: an American population-based cohort study.

Our aim was to assess the risk of cardiovascular disease (CVD) mortality in US 5-year survivors of adolescent and young adult (AYA) cancer compared with those of the general population and contemporaneous 5-year survivors of childhood cancer. A total of 160 834 5-year AYA cancer survivors (aged 15-39 years at diagnosis) were included, representing 2 239 390 person-years of follow-up. Overall, 2910 CVD deaths occurred, which was 1.4-fold [95% confidence interval (CI) 1.3-1.4] that expected in the general population, corresponding to 3.6 (95% CI 3.2-3.9) excess CVD deaths per 10 000 person-years. The highest risk of cardiac mortality was experienced after Hodgkin's lymphoma (HL), and the highest risk of cerebrovascular mortality was observed with central nervous system (CNS) tumours. Even survivors in their 6th and 7th decades of life, the risk of CVD mortality remained markedly higher than that of the matched general population. Competing risk analysis showed that the cumulative mortality of CVD was elevated among AYA cancer survivors compared with childhood cancer survivors during the whole study period. Long-term AYA cancer survivors have a greater risk of CVD mortality than the US general population and childhood cancer survivors. Vulnerable subgroups, especially survivors of HL and CNS tumours, require continued close follow-up care for cardiovascular conditions throughout survivorship.

Dietary iron intake and risk of death due to cardiovascular diseases: A systematic review and dose-response meta-analysis of prospective cohort studies.

Many studies have investigated the association between dietary iron intake and death due to cardiovascular disease (CVD), but the results were inconsistent. We performed a dose-response meta- analysis to quantitatively assess the risk of CVD mortality with dietary intake of iron (total iron, heme iron, and non-heme iron). PubMed and Embase databases were searched for articles published up to February 21, 2019. Prospective cohort studies were included if reporting relative risks (RRs) and 95% confidence intervals (CIs) for risk of CVD mortality associated with dietary iron intake. Restricted cubic splines were used to model the dose-response association. We included eight articles (19 studies including 720,427 participants [46,045 deaths due to CVD]) in the meta-analysis. When comparing the highest versus lowest level of dietary heme iron intake, the pooled RR for CVD mortality was 1.19 (95% CI, 1.01-1.39). With a 1-mg/day increase in dietary heme iron intake, the pooled RR for death due to CVD, stroke, coronary heart disease, and myocardial infarction were 1.25 (95% CI, 1.17-1.33), 1.17 (1.04-1.32), 1.25 (0.70-2.22), and 1.17 (0.55-2.50) respectively. The association between dietary iron intake and CVD mortality was linear (pnonlinearity> 0.05). Higher dietary intake of heme iron was associated with a greater risk of CVD mortality. Reducing consumption of heme iron may help to prevent premature death due to CVD.

Abstract P149: Association Between Disabilities And Cardiovascular Disease Mortality In Diabetic Men And Women

The associations of physical disabilities with cardiovascular disease (CVD) mortality in diabetic patients remains less explored. Purpose: We investigated the associations of activities of daily living (ADL), instrumental ADL (IADL), and functional limitation (FL) disabilities with CVD mortality among diabetic men and women in the National Health and Nutrition Examination Surveys. Methods: Cox proportional hazards regressions were used to examine the associations of ADL, IADL, and FL disabilities with CVD mortality in men and women after adjustment for covariates. We followed 2,255 men and women, aged 20 to 90 years, who participated in the National Health and Nutrition Examination Surveys (1988-1994, 199-2014). All participants completed baseline demographics and health factors, including blood lipid profiles. Diabetes mellitus was defined as fasting glucose level ≥126 mg/dL, a nonfasting glucose level ≥200 mg/dL, use of hypoglycemic agents, or a history of physician-diagnosed diabetes mellitus. ADL disability was defined as those who had any difficulties in dressing, eating, getting out of bed, or walking a room to another room. IADL disability was defined as those who had any difficulties in preparing meals, managing money, or doing chores around the house. FL disability was defined as those who had any limitations in mobility performance (walking 0.25 mile, climbing 10 stairs, lifting/carrying 10 pounds, or standing from a chair). Results: During an average of 15.5 years of follow-up (34,939 person-years), there were a total of 382 CVD deaths. There were direct relationships between the number of ADL, IADL, and FL with CVD mortality after adjustment for age, sex, race, and other CVD risk covariates (All P&lt;0.007). After adjustment for multiple risk factors, the risks of CVD mortality for ADL, IADL, and FL disabilities were (95% CI) 2.01 (1.60, 2.51), 1.99 (1.60, 2.48), and 1.97 (1.59, 2.44), respectively, compared with their counterparts. After further adjustment for chronic medical conditions (personal history of coronary heart disease, stroke, or cancer), diabetic persons with ADL disability had 1.94 times (1.5, 2.43), with IADL disability had 1.93 times (1.54, 2.41), and with FL disability had 1.94 times (1.56, 2.40) the risk of CVD mortality as compared with their counterparts, respectively. The associations remained but were attenuated after further excluding these patients with chronic diseases. The risks of CVD mortality in diabetic persons with ADL, IADL, and FL disabilities were (95% CI) 1.78 (1.30, 2.43), 1.66 (1.22, 2.27), and 1.43 (1.09, 1.89), respectively, compared with their counterparts, after excluding these chronic disease patients. Conclusion: Diabetic persons with ADL, IADL, and FL disabilities had a greater risk of CVD mortality. The American Heart Association should establish exercise and dietary guidelines for diabetic persons with physical disabilities.

Race/Ethnicity and the Prognostic Implications of Coronary ArteryCalcium for All-Cause and Cardiovascular Disease Mortality: The Coronary Artery Calcium Consortium.

BackgroundCoronary artery calcium (CAC) predicts cardiovascular disease (CVD) events; however, less is known about how its prognostic implications vary by race/ethnicity. Methods and ResultsA total of 38 277 whites, 1621 Asians, 977 blacks, and 1349 Hispanics from the CAC Consortium (mean age 55 years, 35% women) were followed over a median of 11.7 years. Modeling CAC in continuous and categorical (CAC=0; CAC 1–99; CAC 100–399; CAC ≥400) forms, we assessed its predictive value for all‐cause and CVD mortality by race/ethnicity using Cox proportional hazards and Fine and Gray competing‐risk regression, respectively. We also assessed the impact of race/ethnicity on risk within individual CAC strata, using whites as the reference. Models were adjusted for traditional cardiovascular risk factors. Increased CAC was associated with higher total and CVD mortality risk in all race/ethnicity groups, including Asians. However, the risk gradient with increasing CAC was more pronounced in blacks and Hispanics. In Fine and Gray subdistribution hazards models adjusted for traditional cardiovascular risk factors and CAC (continuous), blacks (subdistribution hazard ratio 3.4, 95% confidence interval, 2.5–4.8) and Hispanics (subdistribution hazard ratio 2.3, 95% confidence interval, 1.6–3.2) showed greater risk of CVD mortality when compared with whites, while Asians had risk similar to whites. These race/ethnic differences persisted when CAC=0.ConclusionsCAC predicts all‐cause and CVD mortality in all studied race/ethnicity groups, including Asians and Hispanics, who may be poorly represented by the Pooled Cohort Equations. Blacks and Hispanics may have greater mortality risk compared with whites and Asians after adjusting for atherosclerosis burden, with potential implications for US race/ethnic healthcare disparities research.

Early peak height velocity and cardiovascular disease mortality among Icelandic women

Introduction. Early pubertal onset among girls has been associated with cardiovascular disease (CVD) risk factors. We examined whether timing of peak height velocity (PHV), an early marker of maturity, was associated with CVD mortality.Materials and methods. We analysed 973 Icelandic women, born 1921–1935, with annual childhood growth measures from ages 8–13 years, recruited into the longitudinal Reykjavik study 1968–1991. CVD deaths from recruitment to December 2009 were recorded.Results. Eighty-six women died from CVD, 42 deaths from coronary heart disease (CHD). Compared to girls with PHV after age 12, girls with PHV < 11 years and between 11 and 12 years had greater risk of CVD mortality, hazard ratio 1.87 (95% confidence interval 1.07–3.26, P = 0.028) and 2.56 (1.52–4.31, P < 0.001), respectively. Comparable associations were observed with CHD cases 2.27 (1.17–4.44, P = 0.016) as well as non-CHD CVD cases 2.21 (1.17–4.19, P = 0.015) when comparing girls with PHV after versus prior to age 12. Timing of PHV was not associated with traditional CVD risk factors in mid-life including body mass index and adverse lipid profiles or with all-cause mortality.Discussion. Earlier timing of PHV in girls may increase the lifetime risk of CVD mortality and may be an important determinant for later cardiovascular health.

Prehypertension Is Not Associated with All-Cause Mortality: A Systematic Review and Meta-Analysis of Prospective Studies

ObjectivesQuantitative associations between prehypertension or its two separate blood pressure (BP) ranges and cardiovascular disease (CVD) or all-cause mortality have not been reliably documented. In this study, we performed a comprehensive systematic review and meta-analysis to assess these relationships from prospective cohort studies.MethodsWe conducted a comprehensive search of PubMed (1966-June 2012) and the Cochrane Library (1988-June 2012) without language restrictions. This was supplemented by review of the references in the included studies and relevant reviews identified in the search. Prospective studies were included if they reported multivariate-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs) of CVD or all-cause mortality with respect to prehypertension or its two BP ranges (low range: 120–129/80–84 mmHg; high range: 130–139/85–89 mmHg) at baseline. Pooled RRs were estimated using a random-effects model or a fixed-effects model depending on the between-study heterogeneity.ResultsThirteen studies met our inclusion criteria, with 870,678 participants. Prehypertension was not associated with an increased risk of all-cause mortality either in the whole prehypertension group (RR: 1.03; 95% CI: 0.91 to 1.15, P = 0.667) or in its two separate BP ranges (low-range: RR: 0.91; 95% CI: 0.81 to 1.02, P = 0.107; high range: RR: 1.00; 95% CI: 0.95 to 1.06, P = 0.951). Prehypertension was significantly associated with a greater risk of CVD mortality (RR: 1.32; 95% CI: 1.16 to 1.50, P<0.001). When analyzed separately by two BP ranges, only high range prehypertension was related to an increased risk of CVD mortality (low-range: RR: 1.10; 95% CI: 0.92 to 1.30, P = 0.287; high range: RR: 1.26; 95% CI: 1.13 to 1.41, P<0.001).ConclusionsFrom the best available prospective data, prehypertension was not associated with all-cause mortality. More high quality cohort studies stratified by BP range are needed.

Age and Race Impact the Association between BMI and CVD Mortality in Women

In previous studies, we have shown that obesity is associated with increased cardiovascular disease (CVD) mortality in white women but not in black women. Earlier research suggests that body mass index (BMI) has a greater effect on CVD mortality in younger white females than older white females, whereas this relationship in black women is not as clear. This study examines the effect of age on the association of BMI to CVD in black and white women. The Black Pooling Project includes data on 2,843 black women with 50,464 person-years of follow-up, and 12,739 white women with 214,606 person-years of follow-up. A Cox proportional hazards model was used to examine the association between BMI and CVD mortality for specific age/race groups. The younger group was < 60 years of age and the older group was > 60 years of age. In younger white women, the relative risk (95% confidence interval [CI]) for CVD mortality was significant in obese women (BMI > 30 kg/m2) vs. women of normal weight (BMI 18.5-24.9 kg/m2) (1.59 [CI 1.20, 2.09]). Similarly, in older white women, the relative risk for CVD mortality in obese women vs. women of normal weight was significant (1.21 [CI 1.04, 1.41]). There were no such associations for black women. Overweight (BMI 25-29.9 kg/m2) was not associated with increased risk in black or white women. These findings indicate that obesity is associated with a significantly greater risk of CVD mortality among white women, with the strongest association among white women < 60 years of age.

Relation of Lower-Extremity Amputation to All-Cause and Cardiovascular Disease Mortality in American Indians

To compare risk of all-cause and cardiovascular disease (CVD) mortality in people with a lower-extremity amputation (LEA) attributable to diabetes and people without an LEA. The Strong Heart Study is a study of CVD and its risk factors in 13 American-Indian communities. LEA was ascertained at baseline by direct examination of the legs and feet. Mortality surveillance is complete through 2000. Of 2,108 participants with diabetes at baseline, 134 participants (6.4%) had an LEA. Abnormal ankle-brachial index (53%), albuminuria (87%), and long diabetes duration (mean 19.8 years) were common among diabetic subjects with LEA. Mean diabetes duration among diabetic participants without LEA and in those with toe and below-the-knee amputations was 11.9, 18.6, and 21.1 years, respectively. During 8.7 (+/-2.9) years of follow-up, 102 of the participants with LEA (76%) died from all causes and 35 (26%) died from CVD. Of the 1,974 diabetic participants without LEA at baseline, 604 (31%) died from all causes and 206 (10%) died from CVD. The unadjusted hazard ratios (HRs) for all-cause and CVD mortality in diabetic participants with LEA compared with those without were 4.0 and 4.1, respectively. Adjusting for known and suspected confounders, LEA persisted as a predictor of all-cause (HR 2.2, 95% CI 1.7-2.9) and CVD mortality (HR 1.9, 95% CI 1.3-2.9). We observed a significant interaction between baseline LEA and sex on CVD mortality, with female sex conferring added risk of CVD mortality. LEA is a potent predictor of all-cause and CVD mortality in diabetic American Indians. The combination of female sex and LEA is associated with greater risk of CVD mortality than either factor alone.

Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study.

Although the level of hyperglycemia is clearly a risk factor for microvascular complications in diabetic patients, its role in macrovascular complications remains controversial. We followed 4,875 subjects (65% Mexican-American) for 7-8 years to investigate the effects of diabetes and hyperglycemia on all-cause and cardiovascular disease (CVD) mortality. These end points were also analyzed according to quartiles of baseline fasting plasma glucose among diabetic participants. The Cox proportional hazards model was used to estimate the relative risks (RRs) for all-cause and CVD mortality. Diabetes was significantly associated with increased all-cause mortality (RR [95% CI] = 2.1 [1.3-3.5] in men; 3.2 [1.9-5.4] in women) and increased CVD mortality (3.2 [1.4-7.1] in men; 8.5 [2.8-25.2] in women). Among diabetic subjects, those in quartile 4 had a 4.2-fold greater risk of all-cause mortality (P < 0.001) and a 4.7-fold greater risk of CVD mortality (P = 0.01) than those in quartiles 1 and 2 combined. After further adjustment for other potential risk factors, subjects in quartile 4 had a 4.9-fold greater risk of all-cause mortality and a 4.9-fold greater risk of CVD mortality than those in quartiles 1 and 2. In addition, hypertension, current smoking, and cholesterol > 6.2 mmol/l were significant predictors of CVD mortality using Cox models. We conclude that diabetes is a predictor of both all-cause and CVD mortality in the general population and that both hyperglycemia and common CVD risk factors are important predictors of all-cause and CVD mortality in diabetic subjects.