Journal of Personalized Medicine Article Standardized Comparison of Cardiovascular Risk Factors Prevalence in Spanish Women and Men Living with HIV and in the General Population Anna Camps-Vilaró 1,2 , Silvia Pérez-Fernández 1,3 , Isaac Subirana 1,2 , Ramon Teira 4 , Vicente Estrada 5 , Pere Domingo 6 , Irene R. Dégano 1,2,7, *,† and Jaume Marrugat 1,2, *,† 1 REGICOR Study Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona Biomedical Research Park (PRBB), Dr. Aiguader 88, 08003 Barcelona, Spain; acamps@imim.es (A.C.-V.); silvia_medina2712@hotmail.com (S.P.-F.); isubirana@imim.es (I.S.) 2 CIBER of Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain 3 Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain 4 Infectious Diseases Unit, Hospital Sierrallana, 39300 Torrelavega, Spain; ramon.teira1@gmail.com 5 Infectious Diseases Unit, Hospital Clínico San Carlos, 28040 Madrid, Spain; vesda001@gmail.com 6 Department of Infectious Diseases, Hospital de la Santa Creu i Sant Pau, Institut de Recerca del Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; pdomingo@santpau.cat 7 Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Spain  * Correspondence: iroman@imim.es (I.R.D.); jmarrugat@imim.es (J.M.); Tel.: +34-9-3316-0714 (I.R.D.);  +34-9-3316-0733 (J.M.); Fax: +34-9-3316-0796 (I.R.D. & J.M.) † These authors contributed equally to this work. Citation: Camps-Vilaró, A.; Pérez-Fernández, S.; Subirana, I.; Teira, R.; Estrada, V.; Domingo, P.; Abstract: People living with HIV (PLWH) have an increased risk of cardiovascular (CV) disease, Dégano, I.R.; Marrugat, J. likely due to a higher prevalence of CV risk factors. We compared the age-standardized prevalence Standardized Comparison of and management of CV risk factors in PLWH to that of the general population in Spain. Blood Cardiovascular Risk Factors pressure, lipid, glucose, and anthropometric profiles were cross-sectionally compared along with the Prevalence in Spanish Women and treatment of hypertension, dyslipidemia, and diabetes in a general population cohort and a PLWH Men Living with HIV and in the cohort. Prevalence rates were standardized by the direct method by 10-year age groups in European General Population. J. Pers. Med. standard populations and stratified by gender. We included 47,593 individuals aged 35 to 74 years, 2021, 11, 1085. https://doi.org/ 28,360 from the general population cohort and 19,233 from the PLWH cohort. Compared to the 10.3390/jpm11111085 general population, PLWH had a higher concentration of triglycerides (>35 mg/dL in women and >26 mg/dL in men) and a higher prevalence of smoking (>23% and >17%) and diabetes (>9.9% and Academic Editor: Luigi Maria Larocca >8.5%). The prevalence of treated diabetes, hypertension, and dyslipidemia were up to three-fold lower in both women and men living with HIV. There was a significant difference in PLWH compared Received: 6 September 2021 to the general population in the lipid, glucose, and anthropometric profile. In addition, PLWH were Accepted: 23 October 2021 less often treated for diagnosed diabetes, hypertension, and dyslipidemia. Published: 25 October 2021 Keywords: HIV; people living with HIV; prevalence; cardiovascular risk factor; general population Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. 1. Introduction The introduction of combined antiretroviral therapy (cART) in the 1990s significantly reduced the morbidity and increased the survival of people living with HIV (PLWH). cART has become the standard of care for PLWH, leading to lifelong suppression of viral Copyright: © 2021 by the authors. replication. cART has steadily improved undetectable viral load at 48 weeks from 48% Licensee MDPI, Basel, Switzerland. in 1995 to 78% in 2010 and >90% in the most recent analysis [1]. This success has gained This article is an open access article several decades of life expectancy for these patients. As PLWH live longer with their distributed under the terms and disease, they face age-related chronic comorbidities [2]. conditions of the Creative Commons PLWH tend to smoke and develop cardiovascular (CV) diseases, hypertension, dia- Attribution (CC BY) license (https:// betes, and chronic kidney disease more often than the general population [3–5]. PLWH creativecommons.org/licenses/by/ have been reported to have almost 60% greater prevalence of hypertension, coronary artery 4.0/). J. Pers. Med. 2021, 11, 1085. https://doi.org/10.3390/jpm11111085 https://www.mdpi.com/journal/jpm J. Pers. Med. 2021, 11, 1085 2 of 9 disease, peripheral arterial disease, or chronic kidney disease as compared to the general population [6]. This increase is probably due to a combined effect: (1) higher prevalence of CV risk factors; (2) chronic inflammation and immune activation from the host response; (3) adverse events of cART; and (4) metabolic effects induced by HIV infection [7–9]. These factors may also contribute to the management of PLWH and their comorbidities. Half of PLWH have one or more comorbidities and receive at least one medication concomitant to cART [10]. While comparison of CV risk factors’ prevalence in PLWH and the general population has been reported in some studies, age-standardized risk factor prevalence has never been used to control for differences in age distribution. For instance, PLWH tend to be younger than the general population in these studies. Furthermore, few studies have focused on the sex-related distribution of CV risk factors in PLWH, and available results are biased toward men living with HIV (MLWH). Women living with HIV (WLWH) continue to be under-represented in clinical trials and epidemiological studies, despite representing over half of PLWH worldwide, and their socio-economic and clinical conditions can be different than what is observed in men [11,12]. In Spain, the prevalence of HIV infection is lower among women (0.1%) than in men (0.65%), a distribution that is characteristic of high-income countries and prompts differential analysis by sex [13]. The objective of the present study was to compare the age-standardized prevalence and management of CV risk factors in Spanish WLWH and MLWH with that of the Spanish general population. 2. Methods 2.1. Study Design and Population We used a cross-sectional design and two large Spanish cohorts to compare the prevalence of CV risk factors in the general population with that in PLWH aged 35 to 74 years. We excluded individuals outside the defined age range and those records with missing data. For each individual included, we analyzed the most recent measurements available. Data on the general population were obtained from the epidemiology wing of a study of dyslipidemia, atherosclerotic risk, increased high-sensitivity C-reactive protein (hsCRP), and inflammatory and oxidative status (DARIOS study). DARIOS is a pooled cohort of individual data from 11 population cohorts recruited in 10 Spanish autonomous communities in 2000–2010, which included 28,887 participants aged 35 to 74 years at baseline [14,15]. Data on PLWH were obtained from the VACH cohort, a Spanish registry of PLWH consecutively recruited since 1997 at 23 hospital-based HIV clinics nationwide. The VACH cohort includes 29,217 HIV patients who were 16 years or older at hospital admission or at recruitment to the cohort [16,17]. 2.2. Data Collection and Measurements Measurements and questionnaires from the DARIOS and VACH cohorts were obtained during an examination and interview at study inclusion and at their first clinic visit, respectively. Standardized World Health Organization questionnaires [18] were used to collect information on sociodemographic variables, smoking status, and previous history of high blood pressure, dyslipidemia, and diabetes. Physical examinations and blood tests were performed to obtain data on anthropometrics, blood pressure, lipid profile, and glycaemia. Weight, height, and waist circumference were measured by professional healthcare workers. Body mass index (BMI) was calculated as weight divided by squared height (kg/m2 ). Systolic and diastolic blood pressures were measured in seated individuals with an automatic sphygmomanometer after a 5 min rest. Two measures were taken, and the lowest was recorded. Hypertension was defined as previous diagnosis or treatment and/or systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg. J. Pers. Med. 2021, 11, 1085 3 of 9 In DARIOS, blood samples were taken after 10–14 h fasting and stored at −80 ◦ C. Total cholesterol, high-density lipoprotein cholesterol (HDL-c), triglycerides, and glucose were determined using enzymatic methods. Low-density lipoprotein cholesterol (LDL-c) was calculated with the Friedewald equation when triglycerides were <300 mg/dL. Di- abetes was defined as (i) previous diagnosis or treatment or (ii) glucose >125 mg/dL. Quotients of total cholesterol/HDL-c and triglycerides/HDL-c were also calculated. VACH measurements were taken from hospital laboratories’ records. Metabolic syndrome was defined as the presence of three or more of the following five conditions: BMI > 30, waist circumference ≥ 102 cm for men or ≥88 cm for women, triglycerides ≥ 150 mg/dL, HDL-c < 40 mg/dL for men or <50 mg/dL for women, blood pressure ≥ 130/≥85 mmHg, or fasting glucose ≥ 100 mg/dL. 2.3. Statistical Analysis The effect of age differences between the VACH and DARIOS cohorts was controlled by direct standardization of risk factor prevalence using the 1976 European Standard Popu- lation (ESP) [19]. The 1976 ESP was chosen over the 2013 ESP to allow direct comparison with previous publications (we used the weights 14, 14, 11, and 7 for the age groups of 35–44, 45–54, 55–64, and 65–74 years, respectively) [20]. Categorical variables including age-standardized prevalences were described as fre- quencies and compared using the chi-squared test. Continuous variables were described with the mean and 95% confidence interval (CI) and compared using the Student t-test. Triglycerides were log-transformed to normalize their distribution. All statistical analysis was performed with the R software version 3.6.2 [21]. 2.4. Ethics All participants were duly informed and signed their consent to participate. The present study was approved by the Parc de Salut Mar Drug Research Ethics Committee (Authorization CEIm PSMAR 2018/8347-I). 3. Results In this study, we included 47,593 individuals aged 35–74 years, 28,360 from the general population (DARIOS cohort) and 19,233 with HIV (VACH cohort). We excluded 527 individuals from the DARIOS and 9984 from the VACH cohort due to missing data or age out of range (Figure S1). The proportion of women was 53.5% (15,159) in DARIOS and 23.4% (4,495) in VACH (p-value < 0.001). General population individuals were older than PLWH, with a mean age of 54 (95% CI: 53–54) and of 45 (95% CI: 44–45), respectively (p-value < 0.001). Differences in CV risk factor prevalence between women from the general population and WLWH are presented in Table 1. WLWH had significantly higher systolic blood pressure, triglyceride, and glucose concentration levels. WLWH had also higher age- standardized triglycerides/HDL-c quotient and higher prevalence of diabetes, metabolic syndrome, and smoking. WLWH had lower age-standardized concentration of HDL-c, LDL-c, and total cholesterol and lower prevalence of obesity than women from the general population. J. Pers. Med. 2021, 11, 1085 4 of 9 Table 1. Standardized and crude prevalence of cardiovascular risk factors in women from the general population and women living with HIV. Standardized Prevalence Crude Prevalence Cardiovascular Risk General People Living General People Living p-Value p-Value Factor Population with HIV Population with HIV N = 15,159 N = 4495 N = 15,159 N = 4495 Age, years 53.3 (53.2–53.5) 44.0 (43.8–44.2) 0.000 Age categories: 0.000 35–44, % 27.2 (26.5–27.9) 60.0 (58.5–61.4) 45–54, % 26.6 (25.9–27.3) 33.1 (31.7–34.5) 55–64, % 27.0 (26.3–27.7) 5.27 (4.64–5.97) 65–74, % 19.2 (18.6–19.8) 1.69 (1.33–2.11) Systolic blood pressure, 122 (122–123) 125 (123–127) 0.016 124 (123–124) 120 (120–121) <0.001 mmHg Diastolic blood pressure, 75 (75–76) 76 (75–77) 0.14 76 (75–76) 75 (74–75) <0.001 mmHg Hypertension, % 27.4 (26.7–28.0) 28.6 (26.2–30.9) 0.336 29.8 (29.1–30.6) 18.1 (17.0–19.3) <0.001 Treated hypertension, % a 62.7 (60.7–64.7) 21.9 (18.4–25.4) <0.001 74.8 (73.5–76.0) 19.5 (16.9–22.4) <0.001 HDL-c, mg/dL 57 (57–58) 54 (53–56) <0.001 57 (57–58) 53 (52–53) <0.001 LDL-c, mg/dL 136 (135–137) 119 (114–123) <0.001 137 (136–137) 112 (111–113) <0.001 Triglycerides, mg/dL b 99 (99–100) 134 (122–134) <0.001 97.5 (97.5–98.5) 126 (125–129) <0.001 Total cholesterol, mg/dL 214 (213–215) 202 (197–207) <0.001 215 (214–216) 191 (190–193) <0.001 Treated dyslipidaemia, % c 14.0 (13.5–14.6) 9.0 (7.2–10.9) <0.001 15.8 (15.2–16.4) 4.29 (3.72–4.93) <0.001 Total cholesterol/HDL-c 3.9 (3.9–3.9) 4.0 (3.9–4.1) 0.193 3.9 (3.9–3.9) 3.9 (3.8–3.9) 0.704 Triglycerides/HDL-c b 1.7 (1.7–1.8) 2.5 (2.5–2.7) <0.001 1.7 (1.7–1.8) 2.5 (2.5–2.6) <0.001 Glucose, mg/dL 97 (96–97) 100 (97–103) 0.015 97.4 (97.0–97.8) 94.6 (94.0–95.3) <0.001 Diabetes, % 10.6 (10.1–11.1) 20.5 (18.3–22.7) <0.001 11.6 (11.1–12.1) 15.3 (14.2–16.4) <0.001 Treated diabetes, % d 34.4 (31.5–37.2) 12.1 (8.50–15.7) <0.001 45.0 (42.6–47.4) 8.15 (6.22–10.5) <0.001 Body mass index, kg/m2 27.5 (27.4–27.7) 24.0 (23.5–24.6) <0.001 27.7 (27.7–27.8) 23.6 (23.4–23.7) 0.000 Metabolic Syndrome, % 20.5 (19.8–21.1) 24.3 (21.4–27.2) 0.011 22.0 (21.3–22.7) 18.8 (17.3–20.3) <0.001 Smoking, % 21.2 (20.6–21.9) 44.5 (42.5–46.6) <0.001 19.5 (18.9–20.1) 54.7 (53.2–56.2) 0.000 Values are expressed as mean (95% confidence interval). a Among patients with history of hypertension. b Mean (95% confidence interval) were obtained with log-transformed values. c Among all cohort participants. d Among patients with history of diabetes. HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol. On the one hand, the analysis of crude prevalences showed similar results except for the following parameters. Systolic blood pressure, glucose concentration levels, and preva- lence of hypertension and metabolic syndrome were lower in WLWH. On the other hand, concentration of triglycerides, HDL-c, LDL-c, and total cholesterol, triglycerides/HDL-c rate, and prevalences of diabetes, obesity, and smoking were similar between WLWH and the general population. Table 2 presents CV risk factor prevalence in men. Compared to men from the general population, MLWH had a higher concentration of triglycerides, quotient of triglycerides/ HDL-c, and prevalence of diabetes, metabolic syndrome, and smoking, but lower age- standardized blood pressure, HDL-c, LDL-c, and total cholesterol concentrations, quotient of total cholesterol/HDL-c, and prevalence of obesity. When comparing crude and standardized prevalences in MLWH, we found the follow- ing differences. Crude estimates for MLWH yielded lower glucose concentration, hyper- tension, and metabolic syndrome prevalence, and similar concentration of blood pressure, triglycerides, HDL-c, LDL-c, and total cholesterol, quotients of total cholesterol/HDL-c and triglycerides/HDL-c, and prevalence of diabetes, obesity, and smoking than in men from the general population. J. Pers. Med. 2021, 11, 1085 5 of 9 Table 2. Standardized and crude prevalence of cardiovascular risk factors in men from the general population and men living with HIV. Standardized Prevalence Crude Prevalence Cardiovascular Risk General People Living General People Living p-Value p-Value Factor Population with HIV Population with HIV N = 13,201 N = 14,738 N = 13,201 N = 14,738 Age, years 53.8 (53.6–54.0) 45.2 (45.1–45.3) 0.000 Age categories: 0.000 35–44, % 26.3 (25.6–27.1) 52.9 (52.1–53.7) 45–54, % 25.4 (24.7–26.2) 37.0 (36.2–37.7) 55–64, % 27.4 (26.7–28.2) 7.66 (7.24–8.10) 65–74, % 20.8 (20.1–21.5) 2.48 (2.24–2.75) Systolic blood pressure, 130 (129–130) 128 (127–129) <0.001 131 (130–131) 125 (125–126) <0.001 mmHg Diastolic blood pressure, 79 (79–80) 78 (77–78) <0.001 79 (79–80) 77 (77–78) <0.001 mmHg Hypertension, % 29.0 (28.2–29.7) 29.3 (28.1–30.4) 0.676 31.4 (30.6–32.2) 22.3 (21.6–23.0) <0.001 Treated hypertension, % a 59.3 (57.5–61.1) 26.5 (24.7–28.3) <0.001 70.1 (68.7–71.5) 22.2 (20.8–23.6) 0.000 HDL-c, mg/dL 49 (48–49) 46 (45–47) <0.001 48.6 (48.4–48.8) 44.9 (44.6–45.2) <0.001 LDL-c, mg/dL 139 (138–140) 111 (109–113) <0.001 139 (138–139) 106 (106–107) 0.000 Triglycerides, mg/dL b 122 (121–122) 148 (148–149) <0.001 122 (120–123) 147 (145–148) <0.001 Total cholesterol, mg/dL 214 (213–216) 190 (188–192) <0.001 214 (213–214) 182 (182–183) 0.000 Treated dyslipidaemia, % c 15.1 (14.5–15.7) 9.9 (9.0–10.7) <0.001 16.7 (16.0–17.4) 5.85 (5.48–6.24) <0.001 Total cholesterol/HDL-c 4.6 (4.6–4.7) 4.5 (4.4–4.5) <0.001 4.58 (4.56–4.61) 4.40 (4.37–4.43) <0.001 Triglycerides/HDL-c b 2.7 (2.5–2.7) 3.3 (3.3–3.7) <0.001 2.6 (2.5–2.6) 3.4 (3.4–3.5) <0.001 Glucose, mg/dL 104 (103–105) 103 (102–105) 0.324 105 (105–106) 99 (98–99) <0.001 Diabetes, % 15.4 (14.8–16.0) 23.9 (22.8–24.9) <0.001 16.9 (16.3–17.6) 18.3 (17.7–18.9) 0.003 Treated diabetes, % d 40.0 (37.1–42.9) 13.5 (11.9–15.1) <0.001 47.1 (44.9–49.3) 10.1 (9.01–11.3) <0.001 Body mass index, kg/m2 28.1 (27.9–28.2) 24.4 (24.2–24.6) <0.001 28.1 (28.1–28.2) 24.2 (24.1–24.2) 0.000 Metabolic Syndrome, % 27.9 (27.1–28.7) 30.4 (29.0–31.8) 0.002 28.7 (27.9–29.5) 26.1 (25.2–27.1) <0.001 Smoking, % 33.6 (32.8–34.4) 51.3 (50.2–52.5) <0.001 32.3 (31.5–33.1) 57.6 (56.8–58.4) 0.000 Values are expressed as mean (95% confidence interval). a Among patients with history of hypertension. b Mean (95% confidence interval) were obtained with log-transformed values. c Among all cohort participants. d Among patients with history of diabetes. HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol. The percentage of individuals with treated hypertension, diabetes, and dyslipidemia was lower in PLWH than in the general population in both women and men (Tables 1 and 2). In WLWH, we estimated a 2.9-fold decrease in the prevalence of treated hypertension, a 2.8-fold decrease in treated diabetes, and a 1.6-fold decrease in treated dyslipidemia compared to their general population counterparts. Similar differences were observed in MLWH (2.2-, 3.0-, and 1.5-fold decreases, respectively) compared to men in the general population when prevalences were age-standardized. 4. Discussion This study compared CV risk factor prevalence between Spanish PLWH (VACH cohort) and the Spanish general population (DARIOS cohort), stratified by sex and, impor- tantly, standardized for age. The most prevalent CV risk factors observed in PLWH were a higher triglycerides concentration (>35 mg/dL higher in women and >26 mg/dL higher in men) and a higher prevalence of smoking (>23% and >17%, respectively) and diabetes (>9.9% and >8.5%) as compared to the Spanish general population. The higher concentration of triglycerides observed in the VACH cohort agrees with results of the United States study by Önen et al. [22], the Copenhagen study by Gelpi et al. [23], and the French study by Savès et al. [24]. The French cohort was receiving cART with protease inhibitors (PI), which could have increased triglycerides concentration. Most PLWH from the VACH cohort also received cART containing a PI or a nucleoside reverse transcriptase inhibitor (NRTI), which is associated with the development of dyslipidemia and dysregulation in glucose homeostasis [25–29]. J. Pers. Med. 2021, 11, 1085 6 of 9 The difference in metabolic syndrome prevalence between PLWH and the general population is likely due to the higher concentration of triglycerides and prevalence of diabetes and the lower HDL-c concentration observed in PLWH. The increased diabetes prevalence in PLWH observed in our study could possibly be associated with causes similar to the increased triglycerides concentration. Noubissi et al. [5] described an association between cART and diabetes, although Önen et al. [22] and Savès et al. [24] found no difference in diabetes prevalence between PLWH and the general population. The PLWH cohort in our study was less often treated for hypertension, diabetes, and dyslipidemia than the Spanish general population. Prior studies in other countries have yielded contradictory results on this topic. Gelpi et al. [23] described a similar proportion of treated diabetes and hypertension between PLWH and the general population; on the other hand, the PLWH group had more dyslipidemia-treated patients than in the general popu- lation of Copenhagen. In Australia, Dharan et al. [30] also found that PLWH purchased more dyslipidemia medication but observed that fewer PLWH received treatment for diabetes compared with the non-infected population; the authors attributed these findings to differences in population characteristics between the two groups. In the United States, Önen et al. [22] estimated greater prescription of anti-hypertensive and lipid-lowering medications for PLWH than their general population counterparts. Among a number of possible reasons for undertreatment of CV risk factors in PLWH in Spain is the lower efficacy thresholds in PLWH of drugs used for treating metabolic disorders, particularly dyslipidemia [31]. Most of these drugs also have potential interactions with some antiretro- viral drugs, particularly booted PI and non-nucleoside reverse transcriptase inhibitors (NNRTI); this may result in the use of suboptimal doses or slow titration that ultimately have an impact on treatment efficacy. All of these considerations support the need for a more thorough monitoring of CV risk factors in PLWH. Lower HDL-c levels and lower prevalence of hypertension in PLWH were described in the French study by Savès et al. [24]; in contrast, we did not observe a lower prevalence of hypertension in our study. Up to three times less PLWH diagnosed with hypertension and/or diabetes were receiving treatment to manage these chronic conditions in our cohort compared to the general population. The treatment of dyslipidemia was also comparatively lower in PLWH, which can be explained by the lower concentrations of total cholesterol and LDL-c concentrations in PLWH than in the Spanish general population. Many of these previous studies did not stratify PLWH characteristics by sex. Our study is one of the few to estimate CV risk factor prevalence separately in women and in men. Unlike men, WLWH had a higher glucose concentration and systolic blood pressure compared to women from the general population. These differences support the need for stratification by sex in future studies in order to better describe each gender’s characteristics and health necessities. Our findings suggest that previous non-standardized CV risk-factor prevalence com- parisons, such as those discussed above, of PLWH with the general population may have produced biased results due to the large difference of age in both populations. Our analysis pointed to this observation as we observed differences between crude and standardized estimates in both WLWH and MLWH. Standardization controls for the effect of age in different populations and allows for fair comparisons [24,32,33]. We used the direct method with European standard population weights. The results obtained after standardization and stratification by sex yield comparable values for both continuous and categorical factors. 5. Limitations This study has three main limitations. First, its observational and cross-sectional design makes it strictly descriptive. Second, the treatment of dyslipidemia has been computed on the overall populations because the criteria for diagnosis did not match in the DARIOS and VACH cohorts. Third, in the VACH cohort, we have excluded a large number of patients because they were out of the age range or because they had missing J. Pers. Med. 2021, 11, 1085 7 of 9 values in CV risk factors. This fact can only influence our results against our hypothesis since patients with worse management were excluded. 6. Conclusions After appropriate standardization to correct for the effect of age, triglyceride concen- tration and the prevalence of smoking and diabetes were higher in both sexes of PLWH compared to the general population. In addition, glucose concentration and systolic blood pressure were higher in WLWH than in women from the general population. Spanish PLWH were undertreated for diabetes, hypertension, and dyslipidemia compared to the general population. More thorough intervention to address these modifiable risk factors is needed and should become a part of routine HIV care. Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 .3390/jpm11111085/s1, Figure S1: Flow chart of the general population cohort (DARIOS) and the people living with HIV cohort (VACH). Author Contributions: J.M. contributed to the conception or design of the work. R.T., V.E. and P.D. contributed to the acquisition and interpretation of data for the work. A.C.-V., S.P.-F., I.S. and I.R.D. contributed to the analysis and interpretation of data for the work. A.C.-V., I.R.D. and J.M. drafted the manuscript. R.T., V.E., P.D., I.R.D. and J.M. critically revised the manuscript. All gave final approval and agreed to be accountable for all aspects of the work, ensuring integrity and accuracy. All authors have read and agreed to the published version of the manuscript. Funding: This work was supported by Spain’s Ministry of Science and Innovation (Madrid, Spain), co- financed with European Union European Regional Development Funds—ERDF-[CIBERCV CB16/11/ 00229]; the Health Department of the Generalitat de Catalunya (Barcelona, Spain) through the Agència de Gestió d’Ajuts Universitaris de Recerca de Catalunya (AGAUR) (Barcelona, Spain) [2017SGR222]; Instituto de Salud Carlos III (Madrid, Spain) [PI18/00030, PI17/00498, PI14/0700, PI14/0063); Pro- grama de Intensificación de Investigadores del Sistema Nacional de Salud [INT19/00036 to PD]; the strategic plan for research and health innovation (PERIS) (Barcelona, Spain) [SLT006/17/00029 to IRD]; Gilead [IN-ES-985-5373]; and Astrazeneca (grant for the DARIOS Study). CIBER of Cardiovas- cular Diseases (CIBERCV) is an initiative of the Instituto de Salud Carlos III, Madrid, Spain. Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Parc de Salut Mar Drug Research Ethics Committee (Authorization CEIm PSMAR 2018/8347-I). Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Data Availability Statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Acknowledgments: Acknowledgements go to the full roster of DARIOS investigators at www. regicor.org/darios_inv, the full roster of VACH investigators, and Elaine Lilly, English language revision. Conflicts of Interest: J.M. reports grants and consultancy fees from AstraZeneca, Sanofi, Shire, Gilead, Daichii-Sankyo, Genincode, and Ferrer. The other authors declare no conflict of interest. References 1. Lee, F.J.; Amin, J.; Carr, A. 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