Burden of Hyperlipidemia, Cardiovascular Mortality, and COVID‐19: A Retrospective‐Cohort Analysis of US Data

Authors: Hoang Nhat Pham, Ramzi Ibrahim, Enkhtsogt Sainbayar, April Olson, Amitoj Singh, Mohammed Y. Khanji, Justin Lee, Virend K. Somers, Christopher Wenger, C. Anwar A. Chahal, Mamas A. Mamas

Abstract

Background

Hyperlipidemia is a major cardiovascular disease (CVD) risk factor, but there are limited data on its mortality trends in CVD over time. We assessed annual hyperlipidemia‐related CVD mortality trends in the United States, including the COVID‐19 pandemic's impact.

Methods and Results

Mortality data were obtained from the Centers for Disease Control and Prevention repository between 1999 and 2020 among patients ≥15 years old, using International Classification of Diseases, Tenth Revision (ICD‐10) codes for hyperlipidemia (E78.0–E78.5) and CVD (I00–I99). Age‐adjusted mortality rates (AAMRs) per 1 000 000 population were standardized to the 2000 US population. Log‐linear regression models were used to evaluate mortality shifts. Average annual percentage change from 1999 to 2019 was used to project 2020 AAMRs, estimating pandemic‐attributed excess deaths. From 1999 to 2020, 483 155 hyperlipidemia‐related CVD deaths occurred. Despite a general CVD mortality decline, hyperlipidemia‐related CVD AAMRs rose from 36.33 in 1999 to 99.77 in 2019. Ischemic heart diseases (AAMR 49.39) were the leading cause, whereas hypertension had the highest mortality increase (average annual percentage change +10.23%). Mortality rates were higher in men (AAMR 104.87) and non‐Hispanic (AAMR 82.49), and rural populations (AAMR 89.98). Highest mortality was observed in Black populations (AAMR 84.35), those ≥75 years old (AAMR 646.45), and Western US regions (AAMR 96.88). During the first pandemic year, deaths exceeded projections by 10.55%, with notable increases among ages 35 to 75 (14.23%), Hispanic (17.96%), Black (14.82%), and urban (11.68%) groups.

Conclusions

Hyperlipidemia‐related CVD mortality has risen over the past 2 decades, further heightened by the COVID‐19 pandemic, with higher impact on men, Black Americans, the older population, and rural residents. Further study is needed to understand contributing factors and mitigate disparities.

Clinical PerspectiveWhat Is New? Cardiovascular mortality increased consistently in the population with hyperlipidemia between 1999 and 2019, disproportionately affecting men and Black, older, and rural populations.The first year of the COVID‐19 pandemic in 2020 further exacerbated these preexisting disparities, with predominant increases in ischemic heart disease mortality. What Are the Clinical Implications? The findings highlight an urgent need for tailored preventive strategies targeting patients with hyperlipidemia with elevated risks, especially among Black populations, rural communities, and areas of high social vulnerability.

Cardiovascular disease (CVD) is the leading cause of death in the United States, imposing substantial health and economic burden. ^1^ Hyperlipidemia, a well‐established, modifiable CVD risk factor, is an independent predictor for developing cardiovascular events. ^2^ Treatment of hyperlipidemia has been central to targeting the increase in both the prevalence and mortality of CVD, accounting for >4 million global deaths. ^3^

The Social Vulnerability Index (SVI), a measure of social vulnerability, has been linked to CVD through various mechanisms including socioeconomic status, access to health care, and psychosocial stressors. ^4^ , ^5^ , ^6^ , ^7^ , ^8^ , ^9^ Socioeconomic disparities also affect the prevalence and management of hyperlipidemia, with higher SVI associated with an increased prevalence of hyperlipidemia. ^10^ Data exploring the interrelationship between these 3 factors, SVI, CVD outcomes, and hyperlipidemia, remain limited. The COVID‐19 pandemic introduced additional complexity to this relationship by exacerbating existing social vulnerabilities, thereby influencing the burden and mortality of CVD and hyperlipidemia. ^11^ In 2020, the pandemic's first year, there was a significant rise in deaths related to cardiovascular events. ^1^ This increase in mortality, particularly among Asian, Black, and Hispanic populations, could be attributed to both the direct impact of COVID‐19 on microvascular inflammation/dysfunction and the indirect consequences stemming from strained health care systems and hindered access to medical care. ^5^ , ^12^

Understanding the multifaceted interplay between hyperlipidemia as a risk factor for CVD, the impact of social vulnerability, and the additional barriers introduced by the COVID‐19 pandemic is critical for formulating targeted public health interventions to reduce the burden of CVD. We aimed to assess the trends and impact of the SVI and COVID‐19 pandemic on cardiovascular mortality among patients with hyperlipidemia in the United States over the past 22 years.

METHODS

Databases

Anonymized data and materials have been made publicly available at the CDC WONDER (Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research) database and can be accessed at https://wonder.cdc.gov. We performed a retrospective analysis by obtaining mortality and demographic data from the CDC WONDER database. CDC WONDER comprises comprehensive population death counts derived from death certificates of US residents, covering >99% of all deaths in the United States. ^13^ Each death certificate contains a single underlying cause of death and up to 20 additional contributing causes. The underlying cause of death is defined as the disease initiating the train of events leading directly to death, whereas the multiple causes of deaths were classified as diagnoses or problems that contributed to mortality. Causes of death are classified according to the International Classification of Diseases, Tenth Revision (ICD‐10). Demographic data included sex, race, ethnicity, and area of residence. Race (described as non‐Hispanic Black, White, American Indian/Alaska Native, and Asian/Pacific Islander) and ethnicity (described as Hispanic and non‐Hispanic) were recorded on death certificates. Place of residence was categorized into 4 US Census regions (ie, Northeast, Midwest, South, and West) and either urban or rural based on the 2013 National Center for Health Statistics urbanization scheme. ^14^

The 2020 SVI was acquired from the CDC ATSDR (Centers for Disease Control and Prevention's Agency for Toxic Substances and Disease Registry) (https://www.atsdr.cdc.gov). The SVI serves as a metric measuring the preparedness of every US community in response to hazard events including disease outbreaks and national disasters. The CDC ATSDR provides an SVI ranking for each census tract or county‐level based on 16 different social factors grouping into 4 unique themes (Table 1). The SVI is presented as percentile ranking ranging from 0 to 1, with 1 indicating the highest level of social vulnerability. In our analysis, we presented SVI data aggregated into 4 separate groups, spanning from the lowest quartile (Q1, least socially vulnerable) to the highest quartile (Q4, most socially vulnerable). The SVI data were then linked to related county‐level mortality rates using unique county Federal Information Processing Standard (FIPS) codes.

Because the study involved deidentified and publicly available data, institutional review board approval was not required for this study. Our study adhered to the Strengthening the Reporting of Observational studies in Epidemiology guidelines. ^15^ No informed consent was required.

Study Population

All adult decedents (≥15 years old) in the United States, spanning from January 1, 1999 to December 31, 2020, were sourced from the multiple cause of death files using ICD‐10 codes for hyperlipidemia (E78.0–E78.5) as the contributing cause of death and CVD (I00–I99) as the underlying cause of death. Although the preferred term in preventative and lipidology is dyslipidemia, ICD‐10 coding has not reflected this change, and thus the older term hyperlipidemia is used. We further categorized CVD into ischemic heart disease (IHD) (I20–I25), heart failure/cardiomyopathy (HF/cardiomyopathy) (I42, I50), hypertensive disease (I10–I15), and cerebrovascular disease (I60–I69).

Statistical Analysis

Age‐adjusted mortality rates (AAMRs) per 1 000 000 population and 95% CIs were standardized to the 2000 US population using the direct method. ^16^ AAMR was obtained for overall populations with CVD as the underlying cause of death and within each subtype, each including hyperlipidemia as the contributor of death. Mortality data were then stratified by demographics in populations with hyperlipidemia. Proportionate AAMR for each CVD subtype in populations with hyperlipidemia were calculated by dividing the cumulative AAMR of that CVD subtype by the cumulative AAMR of all CVDs in populations with hyperlipidemia. Log‐linear regression models were used for AAMR trend analyses between 1999 and 2019 by fitting trends with the fewest significant joinpoints (joinpoint regression, National Cancer Institute). ^17^ Annual percentage changes (APCs) with 95% CIs were determined through Monte‐Carlo permutation tests for each identified joinpoint segment. ^17^ , ^18^ Average annual percentage changes (AAPCs), reflecting the dynamic AAMR change for the whole 1999 to 2019 period, were calculated by weighing averages of the APCs. Two‐tailed t tests were used to evaluate significant changes in the APC, with a 2‐tailed P value <0.05 indicating statistical significance.

Using the estimated AAPC from 1999 to 2019, we projected the AAMR for 2020, the first year of the pandemic. Excess AAMR was determined by comparing the projected AAMR with the actual AAMR in 2020. The proportion of excess AAMR (presented as a percentage) related to the COVID‐19 pandemic was calculated by dividing the excess AAMR by the actual AAMR in 2020. The estimation of excess deaths was then derived by multiplying the actual number of deaths in 2020 by the proportion of excess AAMR. Furthermore, we calculated SVI‐attributed excess or deficit deaths per 1 000 000 person‐years by estimating the difference in AAMR between the fourth and first SVI quartiles. Associated risk ratios (RRs) and 95% CIs related to higher social vulnerability were estimated using univariable Poisson regression models. Statistical significance was determined for RR‐related CIs that did not include 1.0. Data analysis was performed with Joinpoint trend analysis software (version 5.2.0) and Stata 18 statistical software.

RESULTS

Population Characteristics

Among 18 759 451 CVD deaths in the general population from 1999 to 2020, a total of 483 155 (2.6%) CVD deaths were identified in the context of hyperlipidemia. Of these, 219 830 (45.5%) deaths were in women, and 25 145 (5.2%) deaths were in Hispanic populations. Among non‐Hispanic populations, 419 451 deaths (86.8%) were in White populations, 46 228 deaths (9.6%) in Black populations, 14 981 deaths (3.1%) in Asian/Pacific Islander populations, and 2495 deaths (0.5%) in American Indian/Alaska Native populations. By age, 287 123 (59.4%) deaths were in the age group ≥75 years old, whereas 520 (0.1%) deaths were in young adults (15–35 years old). By specific cardiovascular disease subset among populations with hyperlipidemia, there were 292 798 (60.6%) IHD deaths, 15 210 (3.1%) HF/cardiomyopathy deaths, 60 437 (12.5%) hypertension deaths, and 69 181 (14.3%) cerebrovascular deaths.

Cardiovascular Mortality by Specific CVD Subtype Between 1999 and 2019

Between 1999 and 2020, the mortality rate of all CVD deaths in the general population declined from an AAMR of 4460.73 (95% CI, 4451.77–4469.69) in 1999 to 2729.17 (95% CI, 2723.38–2734.97) in 2019 per 1 000 000 population, with a cumulative AAPC of −2.42% (95% CI, −2.76 to −2.07; P<0.001). In contrast, the AAMR of CVD deaths in populations with hyperlipidemia increased from 36.33 (95% CI, 35.52–37.13) in 1999 to 99.77 (95% CI, 98.67–100.87) in 2019, largely due to increases between 1999 to 2002 (APC +14.96%, P<0.001) and 2002 to 2005 (APC +10.21%, P<0.001) (Figure 1). The cumulative AAMR during this period for CVD mortality in individuals with hyperlipidemia was 80.82 (95% CI, 80.58–81.06), with an AAPC of +5.14% (95% CI, 4.36–5.92, P<0.001).

By specific CVD stratification, mortality rates increased across all CVD subtypes in the setting of hyperlipidemia, with IHD being the most common cause of death (AAMR, 49.39 [95% CI, 49.20–49.57]), followed by cerebrovascular disease (AAMR, 11.60 [95% CI, 11.51–11.69]), hypertension (AAMR, 9.77 [95% CI, 9.69–9.85]), and HF/cardiomyopathy (AAMR, 2.48 [95% CI, 2.44–2.52]) (Figure 2). Hypertension exhibited the highest annual mortality growth among all cardiovascular causes of death (AAPC, +10.23% [95% CI, 9.26–11.20]; P<0.001), followed by HF/cardiomyopathy (AAPC, +8.54% [95% CI, 7.45–9.64]; P<0.001), cerebrovascular disease (AAPC, +6.52% [95% CI, 5.77–7.27]; P<0.001), and IHD (AAPC, +3.51% [95% CI, 2.82–4.19]; P<0.001). Analysis of 1999 to 2019 mortality trends among populations with hyperlipidemia (Table 2) revealed that the increase in mortality in the early 2000s across all CVDs contributed significantly to the upward trends during this IHD (1999–2002 APC +12.74%, P<0.001), cerebrovascular disease (1999–2004 APC +17.70%, P<0.001), hypertension (1999–2004 APC +22.35%, P<0.001), and HF/cardiomyopathy (1999–2004 APC +21.30%, P < 0.001). IHD mortality decreased slightly after 2013, with an APC of −1.04% (P=0.005). Cerebrovascular disease had a consistently higher annual mortality rate compared with hypertension before 2017, but hypertension surpassed cerebrovascular disease during the 2017 to 2020 period.

Among populations with hyperlipidemia, IHD had the highest proportionate mortality among cardiovascular causes of death across all demographic subgroups, with the highest prevalence in men (67.12%) and the 35‐ to 75‐year‐old age group (66.97%). Hypertensive disease remained the second leading cause of death in the Black population (18.21%), whereas cerebrovascular disease was the second most common cause of death in other demographic subgroups. Furthermore, higher hypertension mortality was observed in the 35‐ to 75‐year‐old age group compared with the 75+ age group, irrespective of race (12.42% versus 11.88%) (Figure 3).

Cardiovascular Mortality by Demographic Stratification

Men (AAMR, 104.87 [95% CI, 104.45–105.30]) had higher CVD mortality rates with comorbid hyperlipidemia compared with women (AAMR, 61.93 [95% CI, 61.65–62.20]). The AAPC in men (AAPC, +5.36% [95% CI, 4.52–6.22]; P<0.001) and in women (AAPC, +4.83% [95% CI, 4.42–5.25]; P<0.001) were similar (Figure 4). Older populations (≥75 years old) (AAMR, 646.45 [95% CI, 643.98–648.93]) had significantly higher CVD mortality rates in populations with hyperlipidemia compared with the younger population (35–75 years old) (AAMR, 54.11 [95% CI, 53.86–54.36]). Trend analyses revealed a steeper increase in mortality in individuals ≥75 years old (AAPC, +6.83% [95% CI, 5.99–7.68]) compared with populations 35 to 75 years old (AAPC, +2.94% [95% CI, 2.19–3.68]) (Figure 5).

CVD mortality in the context of comorbid hyperlipidemia was higher among non‐Hispanic populations (AAMR, 82.49 [95% CI, 82.27–82.74]) compared with Hispanic populations (AAMR, 58.98 [95% CI, 58.18–59.77]) (Figure 6A). Mortality was highest among non‐Hispanic Black populations (AAMR, 84.35 [95% CI, 83.52–85.18]), followed by non‐Hispanic White (AAMR, 82.78 [95% CI, 82.51–83.05]), non‐Hispanic American Indian/Alaska Native (AAMR, 76.02 [95% CI, 72.64–79.41]), and non‐Hispanic Asian/Pacific Islander (AAMR, 68.93 [95% CI, 67.73–70.12]) populations. Mortality consistently increased between 1999 and 2019 for non‐Hispanic Black (AAPC, +6.35% [95% CI, 5.62–7.08]; P<0.001) and non‐Hispanic White (AAPC, +5.08 [95% CI, 4.35–5.81]; P<0.001) populations (Figure 6B).

CVD mortality in populations with hyperlipidemia was higher in rural regions (AAMR, 89.98 [95% CI, 89.28–90.48]) compared with urban regions (AAMR, 78.94 [95% CI, 78.68–79.20]). However, rural regions had a similar AAPC (+6.23% [95% CI, 5.28–7.20]; P<0.001) compared with urban regions (+4.91% [95% CI, 4.24–5.59]; P<0.001) (Figure 7). Western US regions (AAMR, 96.88 [95% CI, 96.32–97.45]) had the highest mortality rates in the United States, followed by Midwestern (AAMR, 86.96 [95% CI, 86.44–87.48]), Southern (AAMR, 73.47 [95% CI, 73.09–73.85]), and Northeastern (AAMR, 70.01 [95% CI, 69.52–70.51]) US regions. A similar AAPC was observed among the 4 US Census Northeast (AAPC, +5.17% [95% CI, 4.61–5.74]; P<0.001), Midwest (AAPC, +5.06% [95% CI, 4.25–5.88]; P<0.001), South (AAPC, +5.46% [95% CI, 4.52–6.40]; P<0.001), and West (AAPC, +4.72% [95% CI, 3.57–5.88]; P<0.001).

Cardiovascular Mortality by SVI

CVD AAMRs in populations with hyperlipidemia were higher in US counties categorized as SVI‐Q1 (AAMR, 85.95 [95% CI, 85.28–86.61]) compared with SVI‐Q4 (AAMR 76.18 [95% CI, 75.77–76.59]) (Figure 8). Hispanic and Asian/Pacific Islander populations were impacted by higher mortality in regions with higher social vulnerability, with 9.88 (RR, 1.20 [95% CI, 0.82–1.75]) and 12.71 (RR, 1.26 [95% CI, 0.87–1.85]) excess deaths per 1 000 000 person‐years, respectively. Similarly, populations with high SVI experienced elevated mortality rates in the Western US region (14.11 excess deaths per 1 000 000 person‐years; RR, 1.16 [95% CI, 0.87–1.55]), which was not observed in the other 3 US regions (Northeast, Midwest, and South). Further subgroup analyses did not reveal disparities related to higher social vulnerability in other demographic subgroups (Table 3).

Estimated Excess Mortality in 2020

A total of 4078 excess deaths (10.55% increase) were calculated in 2020 based on the projection of expected AAMR from yearly AAMRs between 1999 and 2019. The primary contributors to these excess deaths were IHD, accounting for more than half with 2258 deaths, followed by cerebrovascular disease (658 deaths), hypertension (598 deaths), and HF/cardiomyopathy (123 deaths). Similar numbers of excess deaths were observed between men (2134 deaths, 9.98% increase) and women (1887 deaths, 10.92% increase). The younger (35–75 years old) population (14.23% increase) experienced a higher relative increase in CVD AAMR compared with the older population (8.03% increase). By race and ethnicity stratification, a higher increase in AAMR was observed in the Hispanic population (17.96% increase) compared with the non‐Hispanic population (10.02% increase), with the highest increases in Black (14.82% increase) and Asian (13.90% increase) populations. Moreover, urban areas saw significantly more excess deaths (3641 deaths, 11.68% increase) compared with rural areas (446 deaths, 5.96%), with the US South region contributing the highest number (1662 deaths) among regions. Populations with SVI‐Q1 had the lowest excess deaths and relative AAMR increase (375 deaths, 7.64% increase). The results for other demographics in the estimate of excess mortality are shown in Table 2.

DISCUSSION

In this retrospective analysis spanning 22 years of data, mortality analysis revealed an upward trend in CVD mortality among patients with hyperlipidemia, contrasting with the decline of CVD mortality in the general population. The primary factor driving the increase in CVD mortality in hyperlipidemia was the rise observed in the early 2000s across all CVD subtypes. Among individuals with hyperlipidemia, IHD was the most common cause of death, whereas hypertension had the highest annual increase in the mortality rate. CVD mortality disproportionately affected men, Black individuals, older populations, rural communities, Western US regions, and high‐SVI populations with hyperlipidemia. The first year of the COVID‐19 pandemic resulted in >10% higher deaths than expected, with the most prominent increase in the 35‐ to 75‐year‐old age group, Hispanic and Black populations, Southern US regions, and urban populations.

In contrast to the overall decline in CVD mortality from 1999 to 2019, there was a rise in CVD mortality among the population with hyperlipidemia, primarily in the early 2000s. This pattern likely reflects a multifactorial interplay, involving increased awareness and screening for hyperlipidemia, advancements in the prevention and management of hyperlipidemia, and changes toward lower diagnostic threshold for hyperlipidemia. ^19^ Analysis of a nationally representative sample (National Health and Nutrition Examination Survey ‐ NHANES), including >50 000 patients from 1999 to 2018, showed consistent rising trends in the proportions of ever cholesterol screening and cholesterol screening within 5 years over the past 2 decades, reaching 81.1% and 72.5%, respectively, by the end of the study period. ^20^ In contrast, the deceleration in hyperlipidemia‐related CVD mortality growth observed in our study, noticeable from 2012 to 2013, may be attributed to the paradigm shift introduced by the 2013 American Heart Association/American College of Cardiology Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. These guidelines prioritize statin therapy for specific beneficiary groups and incorporate atherosclerotic CVD risk estimation into treatment algorithms, rather than adhering to a treat‐to‐target approach focusing on statin intensity and low‐density lipoprotein cholesterol reduction relative to baseline. ^21^ The updated 2018 guidelines not only share many fundamental components of the 2013 guidelines but also strongly support adjunctive nonstatin medication, including newly Food and Drug Administration‐approved PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors, in addition to maximal statin therapy and lifestyle changes for atherosclerotic CVD risk reduction. ^19^ , ^22^ Other factors contributing to the observed trend include improvements in health care systems and better prevention and treatment strategies for CVD, including significant reductions in cigarette smoking, improvements in hypertension treatments, and timely management of acute coronary syndrome. ^23^

Despite the promising decline after 2013, IHD remained the predominant cause of CVD death in individuals with hyperlipidemia, consistent with findings in previous reports. ^24^ Following IHD, hypertension emerged as the second leading cause of CVD death among Black patients and young individuals, irrespective of race, whereas cerebrovascular disease was the second leading cause in other demographic subgroups. This could be explained by the higher prevalence and early onset of hypertension, differences in blood pressure control mechanisms, behavioral characteristics, and other Social Determinants of Health (SDOH) (ie, environment, socioeconomic status, and access to health care) in Black individuals compared with other races. ^25^ The higher hypertension mortality burden in the young population observed in our study was also consistent with prior studies. ^26^ Although not fully understood, several mechanisms underlying this association include genetic predisposition, especially to severe hypertension disease, increased risk of ventricular hypertrophy, coronary calcification, multiple target organ damage, and unawareness of their elevated cardiometabolic risk, which consequently results in elevated mortality risk in patients with younger‐onset hypertension. ^27^

Our analysis showed a higher CVD mortality in men than in women with hyperlipidemia, consistent with previous observations of higher CVD mortality among men in the general population. ^28^ Despite the higher prevalence of hyperlipidemia in women, their lipoprotein profile is considered more atheroprotective compared with men. ^29^ , ^30^ Specifically, men tend to have higher levels of low‐density lipoprotein cholesterol compared with women from puberty to menopause. Although the sex difference in low‐density lipoprotein cholesterol levels diminishes after menopause, men still exhibit a higher low‐density high‐density lipoprotein cholesterol ratio, a predictive and prognostic indicator for atherosclerotic disease, compared with women. ^31^ This could explain the stability of coronary plaques and lower incidence of plaque rupture in women, as demonstrated by the lower IHD mortality in women observed in our study. ^32^ Another contributing factor to higher CVD mortality in men is their high prevalence of CVD risk factors, such as higher tobacco usage and CVD comorbidities. ^28^ Finally, the disparity between sexes in lipid profile screening could also contribute to the underdiagnosis of hyperlipidemia in women, potentially affecting the capture of comprehensive deaths among the population with hyperlipidemia in the Centers for Disease Control and Prevention database. ^33^

A higher CVD mortality rate was observed in the non‐Hispanic population, a previously reported phenomenon known as the Hispanic paradox, wherein Hispanic individuals have lower CVD mortality rates despite a high burden of CVD risk factors and socioeconomic barriers. Several hypotheses have been proposed to explain this phenomenon, including acculturation theory with healthy lifestyles in first‐generation immigrants, the healthy immigrant hypothesis, and the salmon bias theory suggesting underreporting mortality due to return migration. ^34^ In addition, our findings from stratification analysis by social vulnerability showed excess CVD deaths in the Hispanic population with high SVI, which was not observed in non‐Hispanic individuals or other demographic groups. This finding suggests a pronounced degree of SDOH‐related disparity in CVD existing within the Hispanic population with hyperlipidemia. Among non‐Hispanic individuals, the Black population with hyperlipidemia had the highest CVD mortality compared with other racial groups. These persistent racial disparities in CVD mortality, as observed in previous research, are implicated by a complex array of systemic inequities, structural racism, poor health literacy, distrust in the health care system, and comorbidity burden. ^35^ Among these barriers, access to equitable health care plays a significant role, often leading to avoidance of medical care due to financial constraints, as evidenced by the lower prescribing rate of statins even when clinically indicated. ^36^

Similar to prior studies, our study revealed a disproportionate CVD mortality rate in rural compared with urban populations. ^37^ Several factors may contribute to this finding. The rural population was more likely to exhibit key risk factors for CVD, including hyperlipidemia, hypertension, and obesity, predisposing them to develop CVD compared with urban counterparts. ^38^ In addition to the socioeconomic disadvantages and care access inequities in rural areas, the shortage of both primary care and cardiovascular physicians in these regions presents another barrier that could explain the observed rural–urban disparity. ^37^ Previous data showed that only 10% of primary care physicians practice in rural regions despite approximately 20% of Americans living in these regions. ^39^ Stratification analysis by US Census regions reported the Northeast US region exhibited the lowest CVD mortality among all 4 US regions. This observation could be attributed to the superior accessibility in health care, with the highest number of teaching hospitals and medical centers in the Northeast region compared with other regions. ^40^

Our study indicated a >10% higher relative increase in hyperlipidemia‐related CVD mortality in the early COVID‐19 era, with IHD being the main contributor, accounting for 55% of excess deaths. These findings were consistent with prior research showing rapid growth in IHD and hypertension deaths in contrast to the insignificant changes in HF and cerebrovascular disease mortality. ^41^ This increased mortality could be due to the shift in the health care system with resource relocation to patients with COVID‐19 and delayed access with suboptimal care delivery for patients without COVID‐19. Examples include a higher cancellation rate for outpatient cardiovascular visits and delayed medication prescriptions/refills or diagnostic testing. ^42^ Consequently, the true hyperlipidemia‐related CVD mortality burden is likely underestimated, because hyperlipidemia was often underdiagnosed during this period. The higher mortality in IHD might reflect the avoidance of medical care for acute coronary syndrome, delays in emergency response times, and reduction of bystander cardiopulmonary resuscitation, which lead to poor outcomes for these patient populations. ^41^ , ^43^ Furthermore, we also observed an increased risk and burden of hyperlipidemia during the pandemic, likely attributable to multiple behavioral changes, including reduced physical activity, increased sedentary behavior, and alterations in diet; stressors related to the pandemic; and heightened immune and inflammatory responses. These changes thereby have predisposed individuals to cardiometabolic effects, including hyperlipidemia and increased obesity prevalence. ^11^ The disproportionate impact of COVID‐19 on CVD mortality in young, Hispanic, Black, and rural populations in our study is consistent with known socioeconomic and racial and ethnic disparities existing in these populations. The pronounced exacerbation of these disparities during the pandemic may be attributed to low use of medical care, including telemedicine, among these minority groups who are impacted by higher CVD comorbidity burden. Additionally, the worsening of multiple SDOH factors, such as psychosocial stress, food insecurity, and poverty, also likely contributed to this observation. ^44^ , ^45^

This study possesses limitations that need to be considered. The documentation of these vital statistics using death certificates is subject to human errors, including misclassification of cause of death and demographic information, data loss, or errors during compilation. The absence of individual‐level data inherent to the nature of population data, such as comorbidity burden and duration, and medical treatment, precludes the identification of significant confounding factors. Another limitation is the exclusion of COVID‐19 diagnosis in data queries due to potential testing inaccuracies and documentation of COVID‐19 as a cause of death in the first year of the pandemic. The nonlinear nature of historical mortality data poses challenges in modeling and estimating excess mortality in 2020. The unavailability of population‐level data on the triglyceride to high‐density lipoprotein ratio also constitutes a limitation of our study, because this ratio is a well‐established marker of cardiometabolic risk. Despite these limitations, which warrant cautious interpretation of our results, the strength of our study lies in its use of a nationally representative sample, which may be the most reliable source to evaluate the temporal and demographic relationship and the impact of COVID‐19 on hyperlipidemia‐related CVD mortality. Further research is warranted to validate our findings, explore contributing factors, and address health inequalities. This includes an investigation of potential differences in hyperlipidemia between populations vaccinated against COVID‐19 and those who are unvaccinated, and among different types of COVID‐19 vaccines.

CONCLUSIONS

Our study highlights the contemporary trends and disparities of hyperlipidemia‐related CVD mortality and its subtypes over the past 20 years and the impact of the early era of the COVID‐19 pandemic on these disparities. Despite the overall CVD decline in the general population, CVD mortality increased consistently in the population with hyperlipidemia between 1999 and 2019. Certain subpopulations, including men, Black individuals, older individuals, and rural populations, were disproportionately affected by higher mortality. The first year of the COVID‐19 pandemic in 2020 further exacerbated these preexisting disparities, with predominant increases in IHD mortality.

Sources of Funding

None.

Disclosures

None.